VIOLIN: Vaccine Investigation and Online Information Network

Bordetella pertussis

Table of Contents

General Information
Vaccine Related Pathogen Genes
1. TcfA (Other)
2. brkA (Protective antigen)
3. cpn60 (Protective antigen)
4. CyaA (Protective antigen)
5. fhaB (Protective antigen)
6. Prn (Protective antigen)
7. PtxA (Protective antigen)
8. ptxB (Protective antigen)
9. ptxC (Protective antigen)
10. ptxD (Protective antigen)
11. ptxE (Protective antigen)
12. S1 (Protective antigen)
13. aroA (Virmugen)
14. dnt (Virmugen)
Vaccine Related Host Genes
1. IgG
Vaccine Information
References

I. General Information

1. NCBI Taxonomy ID:

520

2. Disease:

Whooping Cough

3. Introduction

Bordetella pertussis is a Gram-negative, aerobic coccobacillus of the genus Bordetella, and the causative agent of pertussis or whooping cough. Pertussis (or Whooping Cough), is an infection of the respiratory system and characterized by a “whooping” sound when the person breathes in. In the US it killed 5,000 to 10,000 people per year before a vaccine was available. Vaccination has transformed this and between 1985-88 fewer than 100 children died from pertussis. Worldwide in 2000, according to the WHO, around 39 million people were infected annually and about 297,000 died. Bordetella pertussis infects its host by colonizing lung epithelial cells. The infection occurs most with children under the age of one when they are unimmunized or children with faded immunity, normally around the age 11 through 18. The signs and symptoms are similar to a common cold: runny nose, sneezing, mild cough, and low-grade fever. The patient becomes most contagious during the catarrhal stage of infection, normally 2 weeks after the coughing begins. It may become airborne when the person coughs, sneezes, or laughs. Pertussis vaccine is part of the DTaP (diphtheria, tetanus, acellular pertussis) immunization. The paroxysmal cough precedes a crowing inspiratory sound characteristic of pertussis. After a spell, the patient might make a “whooping” sound when breathing in, or vomit. Adults have milder symptoms, like prolonged coughing without the “whoop.” Infants less than 6 months may not have the typical whoop. A coughing spell may last a minute or more, producing cyanosis, apnoea and seizures. However, when not in a coughing fit, the patient does not experience trouble breathing. This is because Bordetella pertussis inhibits the immune response and therefore very little mucus is generated in the lungs. A prolonged cough may be irritating and sometimes a disabling cough may go undiagnosed in adults for many months (Wiki: Bordetella pertussis).

4. Microbial Pathogenesis

The bacterium contains a surface protein, filamentous hemagglutinin, which binds to sulfatides that are found on cilia of epithelial cells. Once anchored, the bacterium produces tracheal cytotoxin, which stops the cilia from beating. This prevents the cilia from clearing debris from the lungs, so the body responds by sending the host into a coughing fit. These coughs expel some bacteria into the air, which are free to infect other hosts. Bordetella pertussis has the ability to inhibit the function of the host's immune system. Two toxins, known as the pertussis toxin (or PTx) and adenylate cyclase (CyaA), are responsible for this inhibition. CyaA converts ATP to cyclic AMP, and PTx inhibits an intracellular protein that regulates this process. The end result is that phagocytes convert too much ATP to cyclic AMP, which can cause disturbances in cellular signaling mechanisms, and prevent phagocytes from correctly responding to an infection (Wiki: Bordetella pertussis).

5. Host Ranges and Animal Models

Animal models of pertussis include primates, rats, mice, and rabbits (Salyers and Whitt., 2002).

6. Host Protective Immunity

Acellular pertussis vaccines are effective in providing immunity to whooping cough, by stimulating antibodies to pertussis toxins, as well as an adhesin (Salyers and Whitt., 2002).

II. Vaccine Related Pathogen Genes

1. aroA

Gene Name : aroA
NCBI Protein GI : 144037
Other Database IDs : CDD:179423
CDD:30129
Taxonomy ID : 520
Gene Strand (Orientation) : ?
Protein Length : 442
Protein Note : 3-phosphoshikimate 1-carboxyvinyltransferase; Provisional

Protein Sequence : Show Sequence

>gi|144037|gb|AAA22968.1| 5-enolpyruvylshikimate-3-phosphate synthase (EC 2.5.1.19) [Bordetella pertussis]
MSGLAYLDLPAARLARGEVALPGSKSISNRVLLLAALAEGSTEITGLLDSDDTRVMLAALRQLGVSVGEV
ADGCVTIEGVARFPTEQAELFLGNAGTAFRPLTAALALMGGDYRLSGVPRMHERPIGDLVDALRQFGAGI
EYLGQAGYPPLRIGGGSIRVDGPVRVEGSVSSQFLTALLMAAPVLARRSGQDITIEVVGELISKPYIEIT
LNLMARFGVSVRRDGWRAFTIARDAVYRGPGRMAIEGDASTASYFLALGAIGGGPVRVTGVGEDSIQGDV
AFAATLAAMGADVRYGPGWIETRGVRVAEGGRLKAFDADFNLIPDAAMTAATLALYADGPCRLRNIGSWR
VKETDRIHAMHTELEKLGAGVQSGADWLEVAPPEPGGWRDAHIGTWDDHRMAMCFLLAAFGPAAVRILDP
GCVSKTFPDYFDVYAGLLAARD

Molecule Role : Virmugen
Molecule Role Annotation : An aroA mutant is highly attenuated in mice and induces significant protection from challenge with wild type B. pertussis (Roberts et al., 1990).
Related Vaccine(s): Bordetella pertussis aroA mutant vaccine

2. brkA

Gene Name : brkA
Sequence Strain (Species/Organism) : Bordetella pertussis
VO ID : VO_0011036
NCBI Protein GI : 562026
Other Database IDs : CDD:332715
CDD:238653
CDD:273608
Taxonomy ID : 520
Gene Strand (Orientation) : ?
Protein Name : BrkA
Protein pI : 7.12
Protein Weight : 96022.08
Protein Length : 1066
Protein Note : Domain of Unknown Function (DUF1522); cl27894

Protein Sequence : Show Sequence

>AAA51646.1 BrkA [Bordetella pertussis]
MYLDRFRQCPSSLQIPRSAWRLHALAAALALAGMARLAPAAAQAPQPPVAGAPHAQDAGQEGEFDHRDNT
LIAVFDDGVGINLDDDPDELGETAPPTLKDIHISVEHKNPMSKPAIGVRVSGAGRALTLAGSTIDATEGG
IPAVVRRGGTLELDGVTVAGGEGMEPMTVSDAGSRLSVRGGVLGGEAPGVGLVRAAQGGQASIIDATLQS
ILGPALIADGGSISVAGGSIDMDMGPGFPPPPPPLPGAPLAAHPPLDRVAAVHAGQDGKVTLREVALRAH
GPQATGVYAYMPGSEITLQGGTVSVQGDDGAGVVAGAGLLDALPPGGTVRLDGTTVSTDGANTDAVLVRG
DAARAEVVNTVLRTAKSLAAGVSAQHGGRVTLRQTRIETAGAGAEGISVLGFEPQSGSGPASVDMQGGSI
TTTGNRAAGIALTHGSARLEGVAVRAEGSGSSAAQLANGTLVVSAGSLASAQSGAISVTDTPLKLMPGAL
ASSTVSVRLTDGATAQGGNGVFLQQHSTIPVAVALESGALARGDIVADGNKPLDAGISLSVASGAAWHGA
TQVLQSATLGKGGTWVVNADSRVQDMSMRGGRVEFQAPAPEASYKTLTLQTLDGNGVFVLNTNVAAGQND
QLRVTGRADGQHRVLVRNAGGEADSRGARLGLVHTQGQGNATFRLANVGKAVDLGTWRYSLAEDPKTHVW
SLQRAGQALSGAANAAVNAADLSSIALAESNALDKRLGELRLRADAGGPWARTFSERQQISNRHARAYDQ
TVSGLEIGLDRGWSASGGRWYAGGLLGYTYADRTYPGDGGGKVKGLHVGGYAAYVGDGGYYLDTVLRLGR
YDQQYNIAGTDGGRVTADYRTSGAAWSLEGGRRFELPNDWFAEPQAEVMLWRTSGKRYRASNGLRVKVDA
NTATLGRLGLRFGRRIALAGGNIVQPYARLGWTQEFKSTGDVRTNGIGHAGAGRHGRVELGAGVDAALGK
GHNLYASYEYAAGDRINIPWSFHAGYRYSF

Molecule Role : Protective antigen
Molecule Role Annotation : A soluble fraction obtained from Bordetella pertussis was evaluated as adjuvant for the pertussis component of the Diphtheria-Pertussis-Tetanus (DPT) vaccine. High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. Two proteins were identified as the 73 kDa N-terminal alpha-domain of BrkA autotransporter protein and the Cpn60/60 kDa chaperonin. Both stimulated antibodies against pertussis and induced a 42% protection rate against the challenge (Cainelli et al., 2007).
Related Vaccine(s): B. pertussis BrkA protein vaccine

3. cpn60

Gene Name : cpn60
Sequence Strain (Species/Organism) : Bordetella pertussis
VO ID : VO_0011035
NCBI Protein GI : 968920
Other Database IDs : CDD:234573
CDD:239460
Taxonomy ID : 520
Gene Strand (Orientation) : ?
Protein Name : Cpn60 (GroEL)
Protein pI : 4.81
Protein Weight : 52145.9
Protein Length : 605
Protein Note : chaperonin GroEL; Reviewed; PRK00013

Protein Sequence : Show Sequence

>AAA74967.1 Cpn60 (GroEL) [Bordetella pertussis]
MAAKQVLFADEARVRIVRGVNVLANAVKTTLGPKGRNVVLERSFGAPTVTKDGVSVAKEIELKDKFENIG
AQLVKDVASKTSDNAGDGTTTATVLAQAVVQEGLKYVAAGFNPIDLKRGIDKAVAAAVEELKKLSKPVTT
SKEIAQVGSISANSDASIGQIIADAMDKVGKEGVITVEDGKSLENELDVVEGMQFDRGYLSPYFINSPEK
QVAALDDPYVLIYDKKVSNIRDLLPVLEQVAKSSRPLLIIAEDVEGEALATLVVNNIRGILKTTAVKAPG
FGDRRKAMLEDIAILTGGTVISEETGMSLEKATLQDLGQAKRIEVAKENTTIIDGAGDGKSIEARVKQIR
AQIEEATSDYDREKLQERVAKLAGGVAVIRVGAATEVEMKEKKARVEDALHATRAAVEEGVVPGGGVALL
RAKQAITGLKGDTADQNAGIKLILRAVEEPLRTIVTNAGDEASVVVNTVLNGKGNYGYNAATGEYGDLVE
QGVLDPTKVTRTALQNAASVASLLLTAEAAVVELMENKPAAAPAMPGGMGGMGGMDF

Molecule Role : Protective antigen
Molecule Role Annotation : A soluble fraction obtained from Bordetella pertussis was evaluated as adjuvant for the pertussis component of the Diphtheria-Pertussis-Tetanus (DPT) vaccine. High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. Two proteins were identified as the 73 kDa N-terminal alpha-domain of BrkA autotransporter protein and the Cpn60/60 kDa chaperonin. Both stimulated antibodies against pertussis and induced a 42% protection rate against the challenge (Cainelli et al., 2007).
Related Vaccine(s): B. pertussis Cpn60 protein vaccine

4. CyaA

Gene Name : CyaA
Sequence Strain (Species/Organism) : Bordetella pertussis
VO ID : VO_0011031
NCBI Protein GI : 580668
3D structure: PDB ID : 2COL
Other Database IDs : CDD:281494
CDD:280531
CDD:225483
CDD:305016
Taxonomy ID : 520
Gene Strand (Orientation) : ?
Protein Name : adenylate cyclase
Protein pI : 4.36
Protein Weight : 164358.59
Protein Length : 1785
Protein Note : Anthrax toxin LF subunit; pfam03497

Protein Sequence : Show Sequence

>CAA01202.1 adenylate cyclase [Bordetella pertussis]
MQQSHQAGYANAADRESGIPAAVLDGIKAVAKEKNATLMFRLVNPHSTSLIAEGVATKGLGVHAKSSDWG
LQAGYIPVNPNLSKLFGRAPEVIARADNDVNSSLAHGHTAVDLTLSKERLDYLRQAGLVTGMADGVVASN
HAGYEQFEFRVKETSDGRYAVQYRRKGGDDFEAVKVIGNAAGIPLTADIDMFAIMPHLSNFRDSARSSVT
SGDSVTDYLARTRRAASEATGGLDRERIDLLWKIARAGARSAVGTEARRQFRYDGDMNIGVITDFELEVR
NALNRRAHAVGAQDVVQHGTEQNNPFPEADEKIFVVSATGESQMLTRGQLKEYIGQQRGEGYVFYENRAY
GVAGKSLFDDGLGAAPGVPSGRSKFSPDVLETVPASPGLRRPSLGAVERQDSGYDSLDGVGSRSFSLGEV
SDMAAVEAAELEMTRQVLHAGARQDDAEPGVSGASAHWGQRALQGAQAVAAAQRLVHAIALMTQFGRAGS
TNTPQEAASLSAAVFGLGEASSAVAETVSGFFRGSSRWAGGFGVAGGAMALGGGIAAAVGAGMSLTDDAP
AGQKAAAGAEIALQLTGGTVELASSIALALAAARGVTSGLQVAGASAGAAAGALAAALSPMEIYGLVQQS
HYADQLDKLAQESSAYGYEGDALLAQLYRDKTAAEGAVAGVSAVLSTVGAAVSIAAAASVVGAPVAVVTS
LLTGALNGILRGVQQPIIEKLANDYARKIDELGGPQAYFEKNLQARHEQLANSDGLRKMLADLQAGWNAS
SVIGVQTTEISKSALELAAITGNADNLKSVDVFVDRFVQGERVAGQPVVLDVAAGGIDIASRKGERPALT
FITPLAAPGEEQRRRTKTGKSEFTTFVEIVGKQDRWRIRDGAADTTIDLAKVVSQLVDANGVLKHSIKLD
VIGGDGDDVVLANASRIHYDGGAGTNTVSYAALGRQDSITVSADGERFNVRKQLNNANVYREGVATQTTA
YGKRTENVQYRHVELARVGQVVEVDTLEHVQHIIGGAGNDSITGNAHDNFLAGGSGDDRLDGGAGNDTLV
GGEGQNTVIGGAGDDVFLQDLGVWSNQLDGGAGVDTVKYNVHQPSEERLERMGDTGIHADLQKGTVEKWP
ALNLFSVDHVKNIENLHGSRLNDRIAGDDQDNELWGHDGNDTIRGRGGDDILRGGLGLDTLYGEDGNDIF
LQDDETVSDDIDGGAGLDTVDYSAMIHPGRIVAPHEYGFGIEADLSREWVRKASALGVDYYDNVRNVENV
IGTSMKDVLIGDAQANTLMGQGGDDTVRGGDGDDLLFGGDGNDMLYGDAGNDTLYGGLGDDTLEGGAGND
WFGQTQAREHDVLRGGDGVDTVDYSQTGAHAGIAAGRIGLGILADLGAGRVDKLGEAGSSAYDTVSGIEN
VVGTELADRITGDAQANVLRGAGGADVLAGGEGDDVLLGGDGDDQLSGDAGRDRLYGEAGDDWFFQDAAN
AGNLLDGGDGRDTVDFSGPGRGLDAGAKGVFLSLGKGFASLMDEPETSNVLRNIENAVGSARDDVLIGDA
GANVLNGLAGNDVLSGGAGDDVLLGDEGSDLLSGDAGNDDLFGGQGDDTYLFGVGYGHDTIYESGGGHDT
IRINAGADQLWFARQGNDLEIRILGTDDALTVHDWYRDADHRVEIIHAANQAVDQAGIEKLVEAMAQYPD
PGAAAAAPPAARVPDTLMQSLAVNWR

Molecule Role : Protective antigen
Molecule Role Annotation : A study demonstrated that passive immunization with specific anti-B. pertussis adenylate cyclase antibodies or active immunization with purified B. pertussis secreted adenylate cyclase (cyaA) protect mice against a lethal respiratory challenge with B. pertussis or B. parapertussis. Results suggest that adenylate cyclase might be the primary cytotoxin responsible for mouse pulmonary lesions during respiratory tract infection with B. pertussis or with the related species B. parapertussis and is a protective antigen of B. pertussis (Guiso et al., 1989).
Related Vaccine(s): B. pertussis CyaA protein vaccine

5. dnt

Gene Name : dnt
Sequence Strain (Species/Organism) : Bordetella pertussis Tohama I
NCBI Gene ID : 2666936
NCBI Protein GI : 33594321
Locus Tag : BP3439
Genbank Accession : BX640421
Protein Accession : NP_881965
Taxonomy ID : 257313
Gene Starting Position : 3647083
Gene Ending Position : 3651477
Gene Strand (Orientation) : +
Protein Name : dermonecrotic toxin
Protein pI : 6.49
Protein Weight : 150126.42
Protein Length : 1464
Protein Note : Previously sequenced as Bordetella pertussis dermonecrotic toxin Dnt TR:Q45336 (EMBL: U10527) (1451 aa) fasta scores: E(): 0, 100% id in 1451 aa. Almost identical to Bordetella bronchiseptica dermonecrotizing toxin TR:Q9S5D5 (EMBL: AB020025) (1464 aa) fasta scores: E(): 0, 98.97% id in 1464 aa

DNA Sequence : Show Sequence

>gi|33591275:3647083-3651477 Bordetella pertussis Tohama I, complete genome
CGTGGATAAAGATGAATCGGCATTGCGGCAACTTGTCGACATGGCGCTTGTAGGCTACGACGGCGTGGTG
GAAGAGTTGCTGGCGCTGCCCTCGGAAGAGTCCGGGGATCTTGCGGGTGGACGGGCCAAACGAGAGAAGG
CCGAATTCGCGCTGTTTAGCGAAGCGCCCAACGGGGATGAACCCATCGGCCAGGATGCTCGTACATGGTT
CTATTTTCCCAAGTACCGCCCGGTGGCGGTTTCCAATTTGAAGAAAATGCAGGTGGCGATTCGTGCTCGT
CTCGAGCCTGAGTCATTGATCCTGCAGTGGTTGATCGCACTCGATGTCTATCTCGGCGTGTTGATCGCCG
CCTTGTCCCGCACTGTGATCAGCGACCTGGTATTCGAGTATGTCAAGGCGCGCTACGAGATCTACTACCT
ACTGAATCGCGTGCCGCATCCGCTGGCGACGGCGTACCTCAAGCGCCGCCGCCAGCGTCCGGTGGATCGT
TCGGGACGTCTGGGCTCGGTGTTCGAACACCCGCTATGGTTCGCCTACGACGAATTGGCCGGCACCGTCG
ATCTGGATGCCGACATCTACGAGCAGGCGCTCGCCGAAAGCATCGAACGCCGCATGGACGGAGAGCCGGA
CGACGGCAGTCTGGATACCGCCGAACACGACGTATGGCGTTTGTGCCGCGACGGCATCAATCGGGGCGAG
CAGGCGATTTTCCAGGCATCCGGCCCATATGGCGTGGTCGCGGATGCAGGGTATATGCGCACCGTTGCCG
ATCTGGCGTATGCCGATGCATTGGCGGATTGCCTGCATGCCCAACTGCGCATCCGGGCGCAAGGCTCGGT
CGATAGCCCGGGAGACGAGATGCCACGCAAACTTGATGCGTGGGAAATCGCCAAGTTTCATCTGGCCGCG
ACCCAGCAGGCGCGGGTTGATCTGCTCGAGGCGGCGTTCGCGCTCGACTACGCCGCCTTGCGCGATGTGC
GCGTCTACGGCGATTACCGCAATGCGCTGGCTCTTCGGTTCATCAAGCGCGAGGCCTTGCGGTTGCTGGG
GGCGCGGCGCGGCAACGCCTCTACGATGCCGGCGGTTGCGGCTGGCGAGTACGACGAAATCGTGGCCAGT
GGAGCAGCCAATGACGCGGCTTATGTATCCATGGCCGCCGCGTTGATCGCGGGCGTGCTCTGCGATCTCG
AGAGCGCGCAGCGCACGTTGCCCGTCGTATTGGCCAGGTTTCGGCCCCTTGGCGTGCTTGCGCGATTCAG
AAGGCTGGAGCAGGAAACCGCGGGCATGCTGCTTGGCGACCAGGAGCCGGAGCCTCGGGGCTTCATCAGT
TTTACCGATTTTCGCGATAGCGACGCGTTCGCCAGCTACGCGGAGTATGCGGCCCAGTTCAACGACTATA
TCGATCAATACAGCATACTCGAGGCGCAGCGGCTGGCGCGGATTCTGGCCCTGGGCTCGCGGATGACGGT
CGATCAATGGTGCCTTCCCCTGCAGAAAGTACGGCACTACAAGGTGCTGACATCGCAGCCAGGGCTGATC
GCGCGTGGAATCGAAAATCACAACAGGGGCATTGAATATTGCCTGGGGCGGCCGCCGCTGACCGATCTGC
CGGGTCTTTTCACCATGTTCCAGCTCCATGATTCCAGCTGGCTGTTGGTATCGAACATCAACGGTGAGCT
TTGGTCTGATGTCCTTGCGAACGCTGAGGTGATGCAGAATCCTACGCTGGCCGCCCTTGCCGAGCCGCAA
GGCCGCTTTCGAACCGGCCGTCGAACGGGCGGGTGGTTTCTCGGCGGCCCCGCGACTGAAGGGCCAAGTC
TGCGCGACAACTACCTCCTCAAATTGAGGCAGAGCAATCCGGGGCTGGATGTCAAGAAATGCTGGTATTT
CGGGTATCGGCAAGAGTACAGGCTGCCCGCAGGCGCGCTGGGTGTGCCGCTATTCGCTGTTTCCGTTGCC
CTGAGGCACAGTCTGGACGACCTCGCGGCGCACGCGAAGTCCGCTTTGTACAAACCCAGCGAATGGCAGA
AGTTCGCCTTCTGGATCGTGCCGTTCTACCGGGAAATATTCTTTTCGACCCAGGATCGTTCCTATCGGGT
CGATGTGGGGAGCATCGTCTTTGATTCGATTTCCTTGCTTGCCTCGGTGTTCAGCATAGGAGGGAAGTTG
GGCAGTTTCACCCGTACCCAGTATGGCAACCTGCGCAATTTCGTGGTGCGGCAACGCATCGCGGGGTTGA
GCGGGCAGCGCTTGTGGCGTTCGGTGCTCAAGGAGCTTCCGGCATTGATCGGAGCCAGCGGGTTGCGCCT
GTCGCGTTCGCTGCTCGTCGATCTGTATGAGATCTTCGAGCCCGTGCCTATCCGTCGGCTTGTCGCGGGA
TTCGTGAGCGCCACTACGGTCGGCGGGCGTAACCAGGCCTTCCTGCGGCAGGCATTCTCCGCTGCCAGTT
CCTCGGCCGGGCGCACGGGGGGCCAATTGGCAAGCGAATGGCGGATGGCCGGCGTGGACGCCACCGGTTT
GGTCGAGTCCACGTCGGGCGGCAGGTTTGAGGGCATCTACACGCGCGGCTTGGGACCGTTGAGCGAGTGC
ACCGAGCACTTCATCGTCGAATCCGGGAATGCCTACAGAGTCATCTGGGATGCATACACGCATGGTTGGC
GCGTGGTCAATGGGCGTTTGCCGCCGAGGCTGACCTATACCGTTCCGGTTCGGCTGAACGGGCAAGGCCA
CTGGGAGACGCATCTGGATGTCCCTGGCCGGGGTGGGGCGCCGGAAATCTTCGGACGCATCCGCACGCGT
AATCTGGTCGCCCTTGCCGCCGAGCAGGCCGCGCCGATGCGCCGCCTGCTCAACCAGGCGAGGCGTGTGG
CGCTCAGGCATATCGATACCTGCAGGAGCAGGCTTGCGTTGCCGCGCGCTGAATCCGATATGGACGCGGC
GATCCGGATTTTCTTCGGAGAGCCGGACGCCGGCCTTCGCCAGCGCATCGGGCGACGCCTGCAGGAGGTC
AGGGCCTATATCGGCGATCTGAGTCCGGTCAATGACGTGCTGTACCGGGCGGGATATGACCTCGACGATG
TCGCAACGCTGTTTAACGCAGTGGACCGGAACACGTCGCTGGGCAGGCAGGCTCGGATGGAGTTGTATCT
GGATGCCATTGTCGATTTGCATGCCAGGCTCGGCTATGAAAATGCGCGTTTTGTCGACCTGATGGCGTTC
CACCTGCTCAGCCTGGGCCATGCCGCGACGGCCAGTGAGGTCGTGGAGGCCGTTTCGCCCCGGCTGCTGG
GCAATGTGTTCGATATCTCGAACGTCGCCCAGCTCGAACGCGGTATCGGGAATCCCGCCAGCACCGGTCT
TTTCGTCATGCTGGGCGCCTATTCGGAATCGTCGCCCGCGATATTCCAGTCGTTCGTGAACGATATATTT
CCCGCATGGCGACAGGCTTCCGGCGGGGGGCCGCTGGTATGGAACTTCGGTCCTGCCGCCATCAGCCCGA
CGCGCCTGGATTACGCAAATACCGATATCGGATTGCTCAACCATGGGGATATTTCCCCGCTGCGCGCCAG
GCCGCCATTGGGCGGCAGGCGCGACATCGATCTTCCTCCGGGGCTGGATATTTCGTTCGTGCGTTACGAC
CGCCCGGTGCGCATGTCCGCGCCGCGTGCGCTCGACGCCAGCGTCTTCAGGCCGGTCGACGGGCCTGTCC
ATGGCTATATTCAATCGTGGACGGGGGCTGAGATCGAATATGCGTACGGCGCGCCCGCAGCGGCACGCGA
GGTCATGCTGACCGACAATGTGCGGATCATCAGCATCGAGAACGGCGATGAAGGGGCGATCGGGGTGCGC
GTGAGGCTCGACACTGTTCCCGTCGCGACGCCGCTCATCCTGACTGGCGGCTCCTTGAGCGGGTGCACGA
CGATGGTTGGGGTCAAGGAGGGCTACCTGGCCTTCTACCACACTGGCAAGTCGACCGAACTCGGGGATTG
GGCGACTGCGCGCGAAGGCGTACAGGCGCTTTACCAGGCCCATTTGGCGATGGGGTACGCGCCGATCTCA
ATCCCGGCGCCGATGCGCAATGACGACTTGGTCAGCATCGCCGCGACCTACGACCGGGCGGTCATTGCCT
ATCTGGGCAAGGATGTGCCGGGAGGCGGCAGTACGCGCATAACGCGTCACGATGAGGGGGCGGGCAGTGT
GGTTTCGTTCGACTACAACGCAGCAGTCCAGGCGTCGGCCGTTCCCCGCCTCGGCCAGGTATACGTTCTG
ATTTCCAACGACGGACAAGGGGCGCGAGCCGTCCTGCTGGCGGAGGATCTGGCCTGGGCAGGCAGCGGCA
GTGCCTTGGATGTGTTGAACGAACGATTGGTGACGTTGTTTCCGGCGCCGGTCTG

Protein Sequence : Show Sequence

>gi|33594321|ref|NP_881965.1| dermonecrotic toxin [Bordetella pertussis Tohama I]
MDKDESALRQLVDMALVGYDGVVEELLALPSEESGDLAGGRAKREKAEFALFSEAPNGDEPIGQDARTWF
YFPKYRPVAVSNLKKMQVAIRARLEPESLILQWLIALDVYLGVLIAALSRTVISDLVFEYVKARYEIYYL
LNRVPHPLATAYLKRRRQRPVDRSGRLGSVFEHPLWFAYDELAGTVDLDADIYEQALAESIERRMDGEPD
DGSLDTAEHDVWRLCRDGINRGEQAIFQASGPYGVVADAGYMRTVADLAYADALADCLHAQLRIRAQGSV
DSPGDEMPRKLDAWEIAKFHLAATQQARVDLLEAAFALDYAALRDVRVYGDYRNALALRFIKREALRLLG
ARRGNASTMPAVAAGEYDEIVASGAANDAAYVSMAAALIAGVLCDLESAQRTLPVVLARFRPLGVLARFR
RLEQETAGMLLGDQEPEPRGFISFTDFRDSDAFASYAEYAAQFNDYIDQYSILEAQRLARILALGSRMTV
DQWCLPLQKVRHYKVLTSQPGLIARGIENHNRGIEYCLGRPPLTDLPGLFTMFQLHDSSWLLVSNINGEL
WSDVLANAEVMQNPTLAALAEPQGRFRTGRRTGGWFLGGPATEGPSLRDNYLLKLRQSNPGLDVKKCWYF
GYRQEYRLPAGALGVPLFAVSVALRHSLDDLAAHAKSALYKPSEWQKFAFWIVPFYREIFFSTQDRSYRV
DVGSIVFDSISLLASVFSIGGKLGSFTRTQYGNLRNFVVRQRIAGLSGQRLWRSVLKELPALIGASGLRL
SRSLLVDLYEIFEPVPIRRLVAGFVSATTVGGRNQAFLRQAFSAASSSAGRTGGQLASEWRMAGVDATGL
VESTSGGRFEGIYTRGLGPLSECTEHFIVESGNAYRVIWDAYTHGWRVVNGRLPPRLTYTVPVRLNGQGH
WETHLDVPGRGGAPEIFGRIRTRNLVALAAEQAAPMRRLLNQARRVALRHIDTCRSRLALPRAESDMDAA
IRIFFGEPDAGLRQRIGRRLQEVRAYIGDLSPVNDVLYRAGYDLDDVATLFNAVDRNTSLGRQARMELYL
DAIVDLHARLGYENARFVDLMAFHLLSLGHAATASEVVEAVSPRLLGNVFDISNVAQLERGIGNPASTGL
FVMLGAYSESSPAIFQSFVNDIFPAWRQASGGGPLVWNFGPAAISPTRLDYANTDIGLLNHGDISPLRAR
PPLGGRRDIDLPPGLDISFVRYDRPVRMSAPRALDASVFRPVDGPVHGYIQSWTGAEIEYAYGAPAAARE
VMLTDNVRIISIENGDEGAIGVRVRLDTVPVATPLILTGGSLSGCTTMVGVKEGYLAFYHTGKSTELGDW
ATAREGVQALYQAHLAMGYAPISIPAPMRNDDLVSIAATYDRAVIAYLGKDVPGGGSTRITRHDEGAGSV
VSFDYNAAVQASAVPRLGQVYVLISNDGQGARAVLLAEDLAWAGSGSALDVLNERLVTLFPAPV

Molecule Role : Virmugen
Molecule Role Annotation : A live attenuated B. pertussis vaccine strain BPZE1 that protects mice upon a single intranasal administration was developed by deleting dnt gene (Feunou et al., 2008).
Related Vaccine(s): Bordetella pertussis dnt mutant vaccine

6. fhaB

Gene Name : fhaB
Sequence Strain (Species/Organism) : Bordetella pertussis
VO ID : VO_0011030
NCBI Protein GI : 3980256
3D structure: PDB ID : 1RWR
Other Database IDs : CDD:289765
CDD:283510
CDD:293785
CDD:290071
CDD:292650
GOA:Q45365
InterPro: IPR008619
InterPro: IPR008638
InterPro: IPR010069
InterPro: IPR011050
InterPro: IPR011102
InterPro: IPR012334
UniProtKB/TrEMBL: Q45365
Taxonomy ID : 520
Gene Strand (Orientation) : ?
Protein Name : filamentous hemagglutinin
Protein pI : 9.21
Protein Weight : 332849.05
Protein Length : 3704
Protein Note : Extended Signal Peptide of Type V secretion system; pfam13018

Protein Sequence : Show Sequence

>CAA36409.1 filamentous hemagglutinin [Bordetella pertussis]
MNTNLYRLVFSHVRGMLVPVSEHCTVGNTFCGRTRGQARSGARATSLSVAPNALAWALMLACTGLPLVTH
AQGLVPQGQTQVLQGGNKVPVVNIADPNSGGVSHNKFQQFNVANPGVVFNNGLTDGVSRIGGALTKNPNL
TRQASAILAEVTDTSPSRLAGTLEVYGKGADLIIANPNGISVNGLSTLNASNLTLTTGRPSVNGGRIGLD
VQQGTVTIERGGVNATGLGYFDVVARLVKLQGAVSSKQGKPLADIAVVAGANRYDHATRRATPIAAGARG
AAAGAYAIDGTAAGAMYGKHITLVSSDSGLGVRQLGSLSSPSAITVSSQGEIALGDATVQRGPLSLKGAG
VVSAGKLASGGGAVNVAGGGAVKIASASSVGNLAVQGGGKVQATLLNAGGTLLVSGRQAVQLGAASSRQA
LSVNAGGALKADKLSATRRVDVDGKQAVALGSASSNALSVRAGGALKAGKLSATGRLDVDGKQAVTLGSV
ASDGALSVSAGGNLRANELVSSAQLEVRGQREVALDDASSARGMTVVAAGALAARNLQSKGAIGVQGGEA
VSVANANSDAELRVRGRGQVDLHDLSAARGADISGEGRVNIGRARSDSDVKVSAHGALSIDSMTALGAIG
VQAGGSVSAKDMRSRGAVTVSGGGAVNLGDVQSDGQVRATSAGAMTVRDVAAAADLALQAGDALQAGFLK
SAGAMTVNGRDAVRLDGAHAGGQLRVSSDGQAALGSLAAKGELTVSAARAATVAELKSLDNISVTGGERV
SVQSVNSASRVAISAHGALDVGKVSAKSGIGLEGWGAVGADSLGSDGAISVSGRDAVRVDQARSLADISL
GAEGGATLGAVEAAGSIDVRGGSTVAANSLHANRDVRVSGKDAVRVTAATSGGGLHVSSGRQLDLGAVQA
RGALALDGGAGVALQSAKASGTLHVQGGEHLDLGTLAAVGAVDVNGTGDVRVAKLVSDAGADLQAGRSMT
LGIVDTTGDLQARAQQKLELGSVKSDGGLQAAAGGALSLAAAEVAGALELSGQGVTVDRASASRARIDST
GSVGIGALKAGAVEAASPRRARRALRQDFFTPGSVVVRAQGNVTVGRGDPHQGVLAQGDIIMDAKGGTLL
LRNDALTENGTVTISADSAVLEHSTIESKISQSVLAAKGDKGKPAVSVKVAKKLFLNGTLRAVNDNNETM
SGRQIDVVDGRPQITDAVTGEARKDESVVSDAALVADGGPIVVEAGELVSHAGGIGNGRNKENGASVTVR
TTGNLVNKGYISAGKQGVLEVGGALTNEFLVGSDGTQRIEAQRIENRGTFQSQAPAGTAGALVVKAAEAI
VHDGVMATKGEMQIAGKGGGSPTVTAGAKATTSANKLSVDVASWDNAGSLDIKKGGAQVTVAGRYAEHGE
VSIQGDYTVSADAIALAAQVTQRGGAANLTSRHDTRFSNKIRLMGPLQVNAGGPVSNTGNLKVREGVTVT
AASFDNETGAEVMAKSATLTTSGAARNAGKMQVKEAATIVAASVSNPGTFTAGKDITVTSRGGFDNEGKM
ESNKDIVIKTEQFSNGRVLDAKHDLTVTASGQADNRGSLKAGHDFTVQAQRIDNSGTMAAGHDATLKAPH
LRNTGQVVAGHDIHIINSAKLENTGRVDARNDIALDVADFTNTGSLYAEHDATLTLAQGTQRDLVVDQDH
ILPVAEGTLRVKAKSLTTEIETGNPGSLIAEVQENIDNKQAIVVGKDLTLSSAHGNVANEANALLWAAGE
LTVKAQNITNKRAALIEAGGNARLTAAVALLNKLGRIRAGEDMHLDAPRIENTAKLSGEVQRKGVQDVGG
GEHGRWSGIGYVNYWLRAGNGKKAGTIAAPWYGGDLTAEQSLIEVGKDLYLNAGARKDEHRHLLNEGVIQ
AGGHGHIGGDVDNRSVVRTVSAMEYFKTPLPVSLTALDNRAGLSPATWNFQSTYELLDYLLDQNRYEYIW
GLYPTYTEWSVNTLKNLDLGYQAKPAPTAPPMPKAPELDLRGHTLESAEGRKIFGEYKKLQGEYEKAKMA
VQAVEAYGEATRRVHDQLGQRYGKALGGMDAETKEVDGIIQEFAADLRTVYAKQADQATIDAETDKVAQR
YKSQIDAVRLQAIQPGRVTLAKALSAALGADWRALGHSQLMQRWKDFKAGKRGAEIAFYPKEQTVLAAGA
GLTLSNGAIHNGENAAQNRGRPEGLKIGAHSATSVSGSFDALRDVGLEKRLDIDDALAAVLVNPHIFTRI
GAAQTSLADGAAGPALARQARQAPETDGMVDARGLGSADALASLASLDAAQGLEVSGRRNAQVADAGLAG
PSAVAAPAVGAADVGVEPVTGDQVDQPVVAVGLEQPVATVRVAPPAVALPRPLFETRIKFIDQSKFYGSR
YFFEQIGYKPDRAARVAGDNYFDTTLVREQVRRALGGYESRLPVRGVALVAKLMDSAGTVGKALGLKVGV
APTAQQLKQADRDFVWYVDTVIDGQKVLAPRLYLTEATRQGITDQYAGGGALIASGGDVTVNTDGHDVSS
VNGLIQGRSVKVDAGKGKVVVADSKGAGGGIEADDEVDVSGRDIGIEGGKLRGKDVRLKADTVKVATSMR
YDDKGRLAARGDGALDAQGGQLHIEAKRLETAGATLKGGKVKLDVDDVKLGGVYEAGSSYENKSSTPLGS
LFAILSSTTETNQSAHANHYGTRIEAGTLEGKMQNLEIEGGSVDAAHTDLSVARDARFKAAADFAHAEHE
KDVRQLSLGAKVGAGGYEAGFSLGSESGLEAHAGRGMTAGAEVKVGYRASHEQSSETEKSYRNANLNFGG
GSVEAGNVLDIGGADINRNRYGGAAKGNAGTEEALRMRAKKVESTKYVSEQTSQSSGWSVEVASTASARS
SLLTAATRLGDSVAQNVEDGREIRGELMAAQVAAEATQLVTADTAAVALSAGISADFDSSHSRSTSQNTQ
YLGGNLSIEATEGDATLVGAKFGGGDQVSLKAAKSVNLMAAESTFESYSESHNFHASADANLGANAVQGA
VGLGLTAGMGTSHQITNETGKTYAGTSVDAANVSIDAGKDLNLSGSRVRGKHVVLDVEGDINATSKQDER
NYNSSGGGWDASAGVAIQNRTLVAPVGSAGFNFNTEHDNSRLTNDGAAGVVASDGLTGHVKGDANLTGAT
IADLSGKGNLKVDGAVNAQNLKDYRDKDGGSGGLNVGISSTTLAPTVGVAFGRVAGEDYQAEQRATIDVG
QTKDPARLQVGGGVKGTLNQDAAQATVVQRNKHWAGGGSEFSVAGKSLKKKNQVRPVETPTPDVVDGPPS
RPTTPPASPQPIRATVEVSSPPPVSVATVEVVPRPKVETGSAASASAGGAQVVPVTPPKVEVAKVEVVPR
PKVETAQPLPPRPVVAEKVTTPAVQPQLAKVETVQPVKPETTKPLPKPLPVAKVTKAPPPVVETAQPLPP
VKPQKATPGPVAEVGKATVTTVQVQSAPPKPAPVAKQPAPAPKPKPKPKPKAERPKPGKTTPLSGRHVVQ
QQVQVLQRQASDINNTKSLPGGKLPKPVTVKLTDENGKPQTYTINRREDLMKLNGKVLSTKTTLGLEQTF
RLRVEDIGGKNYRVFYETNK

Molecule Role : Protective antigen
Molecule Role Annotation : A combination of the 69-kDa outer membrane protein and filamentous hemagglutinin (fhaB), both isolated from lymphocytosis promoting factor (LPF; pertussis toxin) minus mutants of Bordetella pertussis, is protective in the mouse intracerebral challenge potency (Kendrick) test (Novotny et al., 1991).
Related Vaccine(s): B. pertussis FhaB and 69 kDa OMP protein vaccine

7. Prn

Gene Name : Prn
Sequence Strain (Species/Organism) : Bordetella pertussis Tohama I
VO ID : VO_0011033
NCBI Gene ID : 2664290
NCBI Protein GI : 33592195
Locus Tag : BP1054
Genbank Accession : BX470248
Protein Accession : NP_879839
Taxonomy ID : 257313
Gene Starting Position : 1098090
Gene Ending Position : 1100822
Gene Strand (Orientation) : +
Protein Name : pertactin autotransporter
Protein pI : 9.61
Protein Weight : 86606.91
Protein Length : 910
Protein Note : Identical to the previously sequenced Bordetella pertussis pertactin precursor Prn or Omp69A SW:PERT_BORPE (P14283) (910 aa) fasta scores: E(): 0, 100% id in 910 aa, and to Bordetella bronchiseptica pertactin precursor Prn SW:PERT_BORBR (Q03035) (911 aa) fasta scores: E(): 1.4e-160, 91.31% id in 921 aa

DNA Sequence : Show Sequence

>NC_002929.2:1098090-1100822 Bordetella pertussis Tohama I chromosome, complete genome
AATGAACATGTCTCTGTCACGCATTGTCAAGGCGGCGCCCCTGCGCCGCACCACGCTGGCCATGGCGCTG
GGCGCGCTGGGCGCCGCCCCGGCGGCGCATGCCGACTGGAACAACCAGTCCATCGTCAAGACCGGTGAGC
GCCAGCATGGCATCCATATCCAGGGCTCCGACCCGGGCGGCGTACGGACCGCCAGCGGAACCACCATCAA
GGTAAGCGGCCGTCAGGCCCAGGGCATCCTGCTAGAAAATCCCGCGGCCGAGCTGCAGTTCCGGAACGGC
AGTGTCACGTCGTCGGGACAGTTGTCCGACGATGGCATCCGGCGCTTTCTGGGCACCGTCACCGTCAAGG
CCGGCAAGCTGGTCGCCGATCACGCCACGCTGGCCAACGTTGGCGACACCTGGGACGACGACGGCATCGC
GCTCTATGTGGCCGGCGAACAGGCCCAGGCCAGCATCGCCGACAGCACCCTGCAGGGCGCTGGCGGCGTG
CAGATCGAGCGCGGCGCCAATGTCACGGTCCAACGCAGCGCCATCGTCGACGGGGGCTTGCATATCGGCG
CCCTGCAGTCATTGCAGCCGGAAGACCTTCCGCCCAGCCGGGTGGTGCTGCGCGACACCAACGTGACCGC
CGTGCCCGCCAGCGGCGCGCCCGCGGCGGTGTCTGTGTTGGGGGCCAGTGAGCTTACGCTCGACGGCGGG
CACATCACCGGCGGGCGGGCAGCGGGGGTGGCGGCCATGCAAGGGGCGGTCGTGCATCTGCAGCGCGCGA
CGATACGGCGCGGGGACGCGCCTGCCGGCGGTGCGGTTCCCGGCGGTGCGGTTCCCGGTGGTGCGGTTCC
CGGCGGCTTCGGTCCCGGCGGCTTCGGTCCCGTCCTCGACGGCTGGTATGGCGTGGACGTATCGGGCTCC
AGCGTGGAGCTCGCCCAGTCGATCGTCGAGGCGCCGGAGCTGGGCGCCGCAATCCGGGTGGGCCGCGGCG
CCAGGGTGACGGTGTCGGGCGGCAGCTTGTCCGCACCGCACGGCAATGTCATCGAGACCGGCGGCGCGCG
TCGCTTTGCGCCTCAAGCCGCGCCCCTGTCGATCACCTTGCAGGCCGGCGCGCATGCCCAGGGGAAAGCG
CTGCTGTACCGGGTCCTGCCGGAGCCCGTGAAGCTGACGCTGACCGGGGGCGCCGATGCGCAGGGCGACA
TCGTCGCGACGGAGCTGCCCTCCATTCCCGGCACGTCGATCGGGCCGCTCGACGTGGCGCTGGCCAGCCA
GGCCCGATGGACGGGCGCTACCCGCGCGGTCGACTCGCTGTCCATCGACAACGCCACCTGGGTCATGACG
GACAACTCGAACGTCGGTGCGCTACGGCTGGCCAGCGACGGCAGCGTCGATTTCCAGCAGCCGGCCGAAG
CTGGGCGGTTCAAGGTCCTGACGGTCAATACGCTGGCGGGTTCGGGGCTGTTCCGCATGAATGTCTTCGC
GGACCTGGGGCTGAGCGACAAGCTGGTCGTCATGCAGGACGCCAGCGGCCAGCACAGGCTGTGGGTCCGC
AACAGCGGCAGCGAGCCGGCCAGCGCCAACACCCTGCTGCTGGTGCAGACGCCACTAGGCAGCGCGGCGA
CCTTTACCCTTGCCAACAAGGACGGCAAGGTCGATATCGGTACCTATCGCTATCGATTGGCCGCCAACGG
CAATGGGCAGTGGAGCCTGGTGGGCGCGAAGGCGCCGCCGGCGCCCAAGCCCGCGCCGCAGCCGGGTCCC
CAGCCGCCGCAGCCGCCGCAGCCGCAGCCGGAAGCGCCGGCGCCGCAACCGCCGGCGGGCAGGGAGTTGT
CCGCCGCCGCCAACGCGGCGGTCAACACGGGTGGGGTGGGCCTGGCCAGCACGCTCTGGTACGCCGAAAG
CAATGCGTTGTCCAAGCGCCTGGGCGAGTTGCGCCTGAATCCGGACGCCGGCGGCGCCTGGGGCCGCGGC
TTCGCGCAACGCCAGCAGCTGGACAACCGCGCCGGGCGGCGCTTCGACCAGAAGGTGGCCGGCTTCGAGC
TGGGCGCCGACCACGCGGTGGCGGTGGCCGGCGGACGCTGGCACCTGGGCGGGCTGGCCGGCTATACGCG
CGGCGACCGCGGCTTCACCGGCGACGGCGGCGGCCACACCGACAGCGTGCATGTCGGGGGCTATGCCACA
TATATCGCCGACAGCGGTTTCTACCTGGACGCGACGCTGCGCGCCAGCCGCCTGGAGAATGACTTCAAGG
TGGCGGGCAGCGACGGGTACGCGGTCAAGGGCAAGTACCGCACCCATGGGGTGGGCGCCTCGCTCGAGGC
GGGCCGGCGCTTTACCCATGCCGACGGCTGGTTCCTCGAGCCGCAGGCCGAGCTGGCGGTATTCCGGGCC
GGCGGCGGTGCGTACCGCGCGGCCAACGGCCTGCGGGTGCGCGACGAAGGCGGCAGCTCGGTGCTGGGTC
GCCTGGGCCTGGAGGTCGGCAAGCGCATCGAACTGGCAGGCGGCAGGCAGGTGCAGCCATACATCAAGGC
CAGCGTGCTGCAGGAGTTCGACGGCGCGGGTACGGTACACACCAACGGCATCGCGCACCGCACCGAACTG
CGCGGCACGCGCGCCGAACTGGGCCTGGGCATGGCCGCCGCGCTGGGCCGCGGCCACAGCCTGTATGCCT
CGTACGAGTACTCCAAGGGCCCGAAGCTGGCCATGCCGTGGACCTTCCACGCGGGCTACCGGTACAGCTG
GTA

Protein Sequence : Show Sequence

>NP_879839.1 pertactin autotransporter [Bordetella pertussis Tohama I]
MNMSLSRIVKAAPLRRTTLAMALGALGAAPAAHADWNNQSIVKTGERQHGIHIQGSDPGGVRTASGTTIK
VSGRQAQGILLENPAAELQFRNGSVTSSGQLSDDGIRRFLGTVTVKAGKLVADHATLANVGDTWDDDGIA
LYVAGEQAQASIADSTLQGAGGVQIERGANVTVQRSAIVDGGLHIGALQSLQPEDLPPSRVVLRDTNVTA
VPASGAPAAVSVLGASELTLDGGHITGGRAAGVAAMQGAVVHLQRATIRRGDAPAGGAVPGGAVPGGAVP
GGFGPGGFGPVLDGWYGVDVSGSSVELAQSIVEAPELGAAIRVGRGARVTVSGGSLSAPHGNVIETGGAR
RFAPQAAPLSITLQAGAHAQGKALLYRVLPEPVKLTLTGGADAQGDIVATELPSIPGTSIGPLDVALASQ
ARWTGATRAVDSLSIDNATWVMTDNSNVGALRLASDGSVDFQQPAEAGRFKVLTVNTLAGSGLFRMNVFA
DLGLSDKLVVMQDASGQHRLWVRNSGSEPASANTLLLVQTPLGSAATFTLANKDGKVDIGTYRYRLAANG
NGQWSLVGAKAPPAPKPAPQPGPQPPQPPQPQPEAPAPQPPAGRELSAAANAAVNTGGVGLASTLWYAES
NALSKRLGELRLNPDAGGAWGRGFAQRQQLDNRAGRRFDQKVAGFELGADHAVAVAGGRWHLGGLAGYTR
GDRGFTGDGGGHTDSVHVGGYATYIADSGFYLDATLRASRLENDFKVAGSDGYAVKGKYRTHGVGASLEA
GRRFTHADGWFLEPQAELAVFRAGGGAYRAANGLRVRDEGGSSVLGRLGLEVGKRIELAGGRQVQPYIKA
SVLQEFDGAGTVHTNGIAHRTELRGTRAELGLGMAAALGRGHSLYASYEYSKGPKLAMPWTFHAGYRYSW

Molecule Role : Protective antigen
Molecule Role Annotation : Researchers constructed isogenic mutants of B. pertussis Tohama expressing the alleles ptxA1 or ptxA2 and prn1 or prn2 and compared the efficacies of an acellular pertussis vaccine against the mutants in a mouse model. While the vaccine was effective against all of the B. pertussis strains regardless of the allele expression pattern, the strain expressing ptxA1 and prn2 displayed a survival advantage over the other strains (Komatsu et al., 2010).
Related Vaccine(s): B. pertussis DNA vaccine encoding Prn

8. PtxA

Gene Name : PtxA
Sequence Strain (Species/Organism) : Bordetella pertussis Tohama I
VO ID : VO_0011034
NCBI Gene ID : 2665068
NCBI Protein GI : 33594638
Locus Tag : BP3783
Genbank Accession : BX470248
Protein Accession : NP_882282
Taxonomy ID : 257313
Gene Starting Position : 3988257
Gene Ending Position : 3989066
Gene Strand (Orientation) : +
Protein Name : pertussis toxin subunit 1
Protein pI : 7.54
Protein Weight : 27989.63
Protein Length : 269
Protein Note : Previously sequenced as Bordetella pertussis pertussis toxin subunit 1 precursor, NAD-dependent ADP-ribosyltransferase, PtxA SW:TOX1_BORPE (P04977) (269 aa) fasta scores: E(): 1.5e-110, 100% id in 269 aa

DNA Sequence : Show Sequence

>NC_002929.2:3988257-3989066 Bordetella pertussis Tohama I chromosome, complete genome
GATGCGTTGCACTCGGGCAATTCGCCAAACCGCAAGAACAGGCTGGCTGACGTGGCTGGCGATTCTTGCC
GTCACGGCGCCCGTGACTTCGCCGGCATGGGCCGACGATCCTCCCGCCACCGTATACCGCTATGACTCCC
GCCCGCCGGAGGACGTTTTCCAGAACGGATTCACGGCGTGGGGAAACAACGACAATGTGCTCGACCATCT
GACCGGACGTTCCTGCCAGGTCGGCAGCAGCAACAGCGCTTTCGTCTCCACCAGCAGCAGCCGGCGCTAT
ACCGAGGTCTATCTCGAACATCGCATGCAGGAAGCGGTCGAGGCCGAACGCGCCGGCAGGGGCACCGGCC
ACTTCATCGGCTACATCTACGAAGTCCGCGCCGACAACAATTTCTACGGCGCCGCCAGCTCGTACTTCGA
ATACGTCGACACTTATGGCGACAATGCCGGCCGTATCCTCGCCGGCGCGCTGGCCACCTACCAGAGCGAA
TATCTGGCACACCGGCGCATTCCGCCCGAAAACATCCGCAGGGTAACGCGGGTCTATCACAACGGCATCA
CCGGCGAGACCACGACCACGGAGTATTCCAACGCTCGCTACGTCAGCCAGCAGACTCGCGCCAATCCCAA
CCCCTACACATCGCGAAGGTCCGTAGCGTCGATCGTCGGCACATTGGTGCGCATGGCGCCGGTGATAGGC
GCTTGCATGGCGCGGCAGGCCGAAAGCTCCGAGGCCATGGCAGCCTGGTCCGAACGCGCCGGCGAGGCGA
TGGTTCTCGTGTACTACGAAAGCATCGCGTATTCGTTCTA

Protein Sequence : Show Sequence

>NP_882282.1 pertussis toxin subunit 1 [Bordetella pertussis Tohama I]
MRCTRAIRQTARTGWLTWLAILAVTAPVTSPAWADDPPATVYRYDSRPPEDVFQNGFTAWGNNDNVLDHL
TGRSCQVGSSNSAFVSTSSSRRYTEVYLEHRMQEAVEAERAGRGTGHFIGYIYEVRADNNFYGAASSYFE
YVDTYGDNAGRILAGALATYQSEYLAHRRIPPENIRRVTRVYHNGITGETTTTEYSNARYVSQQTRANPN
PYTSRRSVASIVGTLVRMAPVIGACMARQAESSEAMAAWSERAGEAMVLVYYESIAYSF

Molecule Role : Protective antigen
Molecule Role Annotation : BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002).
Related Vaccine(s): B. pertussis PTx protein vaccine

9. ptxB

Gene Name : ptxB
Sequence Strain (Species/Organism) : Bordetella pertussis
VO ID : VO_0011037
NCBI Protein GI : 225311180
Other Database IDs : CDD:308828
CDD:280986
GOA:C0MPK7
InterPro: IPR003899
InterPro: IPR005138
InterPro: IPR008992
InterPro: IPR016187
InterPro: IPR020063
UniProtKB/TrEMBL: C0MPK7
Taxonomy ID : 520
Gene Strand (Orientation) : ?
Protein Name : pertussis toxin subunit 2 precursor
Protein pI : 8.37
Protein Weight : 23698.772
Protein Length : 302
Protein Note : Aerolysin/Pertussis toxin (APT) domain; pfam03440

Protein Sequence : Show Sequence

>CAX52304.1 pertussis toxin subunit 2 precursor [Bordetella pertussis]
MPIDRKTLCHLLSVLPLALLGSHVARASTPGIVIPPQEQITQHGGPYGRCANKTRALTVAELRGSGDLQE
YLRHVTRGWSIFALYDGTYLGGEYGGVIKDGTPGGAFDLKTTFCIMTTRNTGQPATDHYYSNVTATRLLS
STNSRLCAVFVRSGQPVIGACTSPYDGKYWSMYSRLRKMLYLIYVAGISVRVHVSKEEQYYDYEDATFET
YALTGISICNPGSSLC

Molecule Role : Protective antigen
Molecule Role Annotation : BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002).
Related Vaccine(s): B. pertussis PTx protein vaccine

10. ptxC

Gene Name : ptxC
Sequence Strain (Species/Organism) : Bordetella pertussis
VO ID : VO_0011038
NCBI Protein GI : 225311183
Other Database IDs : CDD:308828
CDD:280986
GOA:Q546I1
InterPro: IPR003899
InterPro: IPR005138
InterPro: IPR008992
InterPro: IPR016187
InterPro: IPR020063
UniProtKB/TrEMBL: Q546I1
Taxonomy ID : 520
Gene Strand (Orientation) : ?
Protein Name : pertussis toxin subunit 3 precursor
Protein pI : 8.76
Protein Weight : 24184.712
Protein Length : 303
Protein Note : Aerolysin/Pertussis toxin (APT) domain; pfam03440

Protein Sequence : Show Sequence

>CAX52307.1 pertussis toxin subunit 3 precursor [Bordetella pertussis]
MLINNKKLLHHILPILVLALLGMRTAQAVAPGIVIPPKALFTQQGGAYGRCPNGTRALTVAELRGNAELQ
TYLRQITPGWSIYGLYDGTYLGQAYGGIIKDAPPGAGFIYRETFCITTIYKTGQPAADHYYSKVTATRLL
ASTNSRLCAVFVRDGQSVIGACASPYEGRYRDMYDALRRLLYMIYMSGLAVRVHVSKEEQYYDYEDATFQ
TYALTGISLCNPAASIC

Molecule Role : Protective antigen
Molecule Role Annotation : BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002).
Related Vaccine(s): B. pertussis PTx protein vaccine

11. ptxD

Gene Name : ptxD
Sequence Strain (Species/Organism) : Bordetella pertussis
VO ID : VO_0011032
NCBI Protein GI : 225311181
Other Database IDs : CDD:286372
GOA:C0MPK8
InterPro: IPR008992
InterPro: IPR015355
UniProtKB/TrEMBL: C0MPK8
Taxonomy ID : 520
Gene Strand (Orientation) : ?
Protein Name : pertussis toxin subunit 4 precursor
Protein pI : 10.82
Protein Weight : 15542.962
Protein Length : 227
Protein Note : Pertussis toxin S4 subunit; pfam09275

Protein Sequence : Show Sequence

>CAX52305.1 pertussis toxin subunit 4 precursor [Bordetella pertussis]
MLRRFPTRTTAPGQGGARRSRVRALAWLLASGAMTHLSPALADVPYVLVKTNMVVTSVAMKPYEVTPTRM
LVCGIAAKLGAAASSPDAHVPFCFGKDLKRPGSSPMEVMLRAVFMQQRPLRMFLGPKQLTFEGKPALELI
RMVECSGKQDCP

Molecule Role : Protective antigen
Molecule Role Annotation : BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002).
Related Vaccine(s): B. pertussis PTx protein vaccine

12. ptxE

Gene Name : ptxE
Sequence Strain (Species/Organism) : Bordetella pertussis
VO ID : VO_0011039
NCBI Protein GI : 225311182
Other Database IDs : CDD:286373
GOA:C0MPK9
InterPro: IPR008992
InterPro: IPR015356
UniProtKB/TrEMBL: C0MPK9
Taxonomy ID : 520
Gene Strand (Orientation) : ?
Protein Name : pertussis toxin subunit 5 precursor
Protein pI : 6.49
Protein Weight : 14292.102
Protein Length : 207
Protein Note : Pertussis toxin S5 subunit; pfam09276

Protein Sequence : Show Sequence

>CAX52306.1 pertussis toxin subunit 5 precursor [Bordetella pertussis]
MQRQAGLPLKANPMHTIASILLSVLGIYSPADVAGLPTHLYKNFTVQELALKLKGKNQEFCLTAFMSGRS
LVRACLSDAGHEHDTWFDTMLGFAISAYALKSRIALTVEDSPYPGTPGDLLELQICPLNGYCE

Molecule Role : Protective antigen
Molecule Role Annotation : BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002).
Related Vaccine(s): B. pertussis PTx protein vaccine

13. S1

Gene Name : S1
Sequence Strain (Species/Organism) : Bordetella pertussis Tohama
NCBI Protein GI : 3152313
Other Database IDs : CDD:111768
GOA:Q599G4
HSSP: P04977
InterPro: IPR003898
UniProtKB/TrEMBL: Q599G4
Taxonomy ID : 520
Gene Strand (Orientation) : ?
Protein Name : toxin subunit S1
Protein pI : 7.49
Protein Weight : 28321.94
Protein Length : 326
Protein Note : Pertussis toxin, subunit 1; pfam02917

Protein Sequence : Show Sequence

>CAA06899.1 toxin subunit S1 [Bordetella pertussis]
MRCTRAIRQTARTGWLTWLAILAVTAPVTSPAWADDPPATVYRYDSRPPEDVFQNGFTAWGNNDNVLDHL
TGRSCQVGSSNSAFVSTSSSRRYTEVYLEHRMQEAVEAERAGRGTGHFIGYIYEVRADNNFYGAASSYFE
YVDTYGDNAGRILAGALATYQSEYLAHRRIPPENIRRVTRVYHNGITGETTTTEYSNARYVSQQTRANPN
PYTSRRSVASIVGTLVRMAPVIGACMARQAESSEAMAAWSERAGEAMVLVYYESIAYSF

Molecule Role : Protective antigen
Related Vaccine(s): B. pertussis DNA vaccine pcDNA/S1

14. TcfA

Gene Name : TcfA
Sequence Strain (Species/Organism) : Bordetella pertussis
NCBI Protein GI : 282766137
Other Database IDs : CDD:154874
Taxonomy ID : 520
Gene Strand (Orientation) : ?
Protein Name : tracheal colonization factor
Protein pI : 5.91
Protein Weight : 62423.78
Protein Length : 631
Protein Note : Autotransporter beta-domain; cl02365

Protein Sequence : Show Sequence

>gi|282766137|gb|ADA85103.1| tracheal colonization factor [Bordetella pertussis]
MHIYGNMNRATPCRGAVRALALALLGAGMWTLSPPSAWALKLPSLLTDDELKLVLPTGMSLEDFKRSLQE
SAPSALATPPSSSPPVAKPGPGSVAEAPSGSGHKDNPSPPVVGVGPGMAESSGGHNPGVGGGTHENGLPG
IGKVGGSAPGPDTSTGSGPDAGMASGAGSTSPGASGGAGKDAMPPSEGERPDSGMSDSGRGGESSAGGLN
PDGAGKPPREEGEPGSKSPADGGQDGPPPPRDGGDADPQPPRDDGNGEQQPPKGGGDEGQRPPPAAGNGG
NGGNGNAQLPERGDDAGPKPPEGEGGDEGPQPPQGGGEQDAPEVPPVAPAPPAGNGVYDPGTHTLTTPAS
AAVSLASSSHGVWQAEMNALSKRMGELRLTPVAGGVWGRAFGRRQDVDNRVSREFRQTISGFELGADTAL
PVADGRWHVGAVAGYTNGRIKFDRGGTGDDDSVHVGAYATYIEDGGFYMDGIVRVSRIRHAFKVDDAKGR
RVRGQYRGNGVGASLELGKRFTWPGAWYVEPQLEVAAFHAQGADYTASNGLRIKDDGTNSMLGRLGLHVG
RQFDLGDGRVVQPYMKLSWVQEFDGKGTVRTNDIRHKVRLDGGRTELAVGVASQLGKHGSLFGSYEYAKG
S

Molecule Role : Other
Molecule Role Annotation : Intranasal administration of IEM101 expressing Tcf induced a significant reduction in bacterial colonization of the tracheas of mice challenged with wild-type B. pertussis. These data are in agreement with the putative role of Tcf in Bordetella tracheal colonization (Chen et al., 1998).
Related Vaccine(s): VC-TetC/Tcf

III. Vaccine Related Host Genes

1. IgG

Gene Name : IgG
Sequence Strain (Species/Organism) : Mus musculus
NCBI Gene ID : 16059
Genbank Accession : AF010213
Taxonomy ID : 10090
Chromosome No : 12
Gene Starting Position : 881411
Gene Ending Position : 914690
Gene Strand (Orientation) : +
Protein Name : immunoglobulin heavy chain (V7183 family)
Protein Note : Also known as IgG; IgH; VI24H; VH7183; B9-scFv; IgVH1(VSG)

DNA Sequence : Show Sequence

>gi|94393741:881411-914690 Mus musculus strain 129/SvJ chromosome 12 unlocalized genomic contig, MGSCv37 alternate locus group 129/SvJ
CATGGACTTTGGGCTCAGCTGTGTTTTCCTTGTCCTCATTTTAAGAGGTAATTTGTAGAAATAAGATCCT
GCCAGTATTGTGTACAGGAGAAATAGAAAAATTTTTCTTTCCTCTATTTTGTTTTGTTTTGTTAGTGACA
GTTTACAAATAAGCATTCTCTGTTGTGAGGTGCCCAGTGTGAGGTGAAGATGGTGGAGTCTGTGGGAGGC
TTAGTGCAGCCTGTAGGGTCATTGAAACCCTCCTGTGCAGCCTCTGGATTCATTCTCACTGACTACTGAA
TGACCTGGATCCTTCAGGCTTCAAAGAAAAGGATGGAGAGGGTGACAATAAAATTTTTCCCACTCACACC
CACTTGCTGGCCCTGGCGTTCCCCTGTAATGAGGCACATAAAGTTTGCAAAACCAAGGGGCCTCTCTTCT
CAATGATGGCTGACTAGGACATCTTCTGATACATATGCAGCTAGAGACATGAGCTCCCGGGATACTGGTT
ACTTCATATTGTTGTTCCCCCACAACAGTTGCAGACCCTTTTATTTCTGTGGGTACTTTCACTAGCTCCT
CCATTGGGGGCCCTGTGTTCCATCCAATAGCTGACTGTGAGCATCCACTTCTGTAGTTGCTAGGCCCCGG
CATAGCCTCACAAGAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTTGCTGGTGTATGCAATGGTGTC
AGAGTTTGGAGTCTGATTATGGGATGGATCCCCAGGTATGGCAAACTCTAGATGGTCCATCCTTTCCCAA
CAATAATTTTTAATGGTGGAGATAGCACCTACTATCCAGACACAATGAAGGGCCAATTCACTATCTCTAG
AGATGATGCCAAAAACACACTTTACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTATACA
TATATTCCTAAGCTTGAGTAAGTGGACTTAAACTGATTCCATCACAACTTGCATGAGATGGATATTCCCC
AGTGTTAAGACCTGTCACCATCACTGTCAATCAGAAGACAAAGTTTATGCACAACAAAACAAAAAAACCA
AAAGCAGAGGCCTCCAATTACAAGTAATAGACCCAGACCCACAGTCTCTGAAAACTGACTGTACAGTTGG
ATCCAGTCTTTTACTTCTTTTCCCTGGATTTTATATTACTGAGGAAATGAGGAAAGCTCTACAATATCTG
TTCTCCATAGTGCTCAACACCTCCAAGCACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTTCTT
GTCTTGTAGACTACTTCAACCTATTTTGTACTCCAGTTAATGAAACTCAAGTCTAGCAGCCTGTCACTGT
TTATTCTAAAGTATTATGAACAGGTGACCTCCCATCCTTCCCCAACGCAATAATCATATTTAGGAATTTG
AGGTTTTATGAGATATGATCTCAGGGTAGAGAGAGAAAGCAAACTACATAGAAATATAGACTGACATAAA
TCAAGACTTGCATAAGCTAGTCCCCAAGTTCCATGTCCCTAAGTGGCAAGGACTATCTTCTGAGCCTAAT
GAGATGAGATCCAAATCAAACCTCCTGGGTCTTTTTAGATAAACATGTGAGATCAATAGACTAAATGCTT
TGGCTGGGCTTCCTTGCAATCCAATTCCCAAACAAAAATGGATCTGGCTCCACAGACACCACAAGAATAG
TCTTAAATAGTTCTTTAAGTAGAATGTCTGATCACTACGAGCCCAATTCCATCCTAAATACTCTTCTGGA
TTATACATAAATAAAAATTGAACATAGGGCATGGGGCACTGATCTCCCTGTGCTACATGAATGGGGGCTC
ATTTACTAAATGTTCCCATTTTTCTTTCTAGCGCTGCACAGTGCAAATCCTACAACTTCCTGTTTATCTA
CAATGTGAACTCCAAACAGTACAAGAAAAAACGTTCCTTATGTTCCTCTCCAGGTTCTCCAACAAGCACA
GAGCAACCTTCTGTCACCAGGACGGAAAACTGGAAACCTTGCTCACTGCTTCCTTTTATTCCCTCGGGAA
CCTCCCCCAATGCAAAGCAGCCCTCAGGCAGAGGATAAAAGCTCACACAAAGACGAGAAGCCCCATCCTC
TTCTCATAGAGCATCCATCAGAGCATGGCTGTCCTGGGGCTGCTTCTCTGCCTGGTGACTTTCCCAAGCT
GTAAGTGTTTCAGGGTTTCAGAAGAGGGACTAAGACATGTCAGCTAGAAGATGTGTGACTAATGGTGATG
TTGCTTGTCCCCAGGTGTCCTGTCCCAGGTGCAGCTGAAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCA
CAGAGCCTGTCCATCACATGCACCGTCTCAGGGTTCTCATTAACTAGCTATGGTGTACACTGGGTTCGCC
AGCCTCCAGGAAAGGGTCTGGAGTGGCTGGTAGTGATATGGAGTGATGGAAGCACAACCTATAATTCAGC
TCTCAAATCCAGACTGAGCATCAGCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTC
CAAACTGATGACACAGCCATGTACTACTGTGCCAGAAACACAGTGTGGGAAGTCCAATGTGAGCCTGCAC
AAATACTTCTCTGCAGGGATGATCACAACCAGCAGGGGGCGCTGATGACCCAAAGGGACTTCCCAGGATC
TCTTCTGGAATCTAGGGAGTTCTGGCCTGTGTCTATCAGCATGTGTTTCAATGTTAGAGTTGTGAGTTTT
CCTTCCAGCAACAGAGATATTTTAGAGCCCACTTTTCATGGTCATTCTACTAAATTTGTTCACATAGTGG
AAAGATTTGTTAAATGATTCTATAGTCTAATAGGGTCAAACAAAAACAAATAATTGAGTTCATATCTACC
AAAAAAAAAAAAATTCCCTCAAAGTGGACAACTGTGTAGGTGAGGAAAACCAGGGGGATTTGGGAATAGA
TTATTTCTCTCCCGACTGTGGTGTTAGTCACCTTTCAGCCATTTACTGTATTTAATTCATGTTTAAAGTT
AATTGTATTCATCTTCCCTAACATGAAGTTTTCAAACACATGTCCACAATTTAATGATGACACAGTTATC
ATTGTGAATGATAACTCATAAGATCTCTCTCCATATATGAAACACACGATATTCTGTTATTAGCTATAGC
CAACAAAGTTACATATCATTATTATTACTGAAATAATTCTTCCCATCTAACTGAATAGTTTTCTCACTCG
ACACTGCCTATGCTGCGATCAGCCTGCTCTAATTTTACCTTTGCTCAGAGCACTGCTTTCTGTTTCATTT
GATAAGATGGTGCCTGGTTGTCACTGAAAATGTGTCCTCCAGTTTCACAGTGATTAATGTGATTTTCAGT
ACATTGAGAACAGAGCCACAGCAAAAATGAGATGGAATGTCATCATTTTTACGCCAGGTGCTGCAGAAAT
AGCTAGGTGGTTAAGAGAGAATATTGAACTTTGAGGGGTTCAGATTAAATTCCTGATACCCACAATGTGC
ACCTCATAACCACATGTACATATAGAAAACTCAGTATAAATGTGGCCTCCGTGAGCACCACACTACTCCC
ACAAACACATATACACATAATTAAAAGTAAAGATTTTAGAAAAATGGCTAATCTAATGATAGGAAGTAGT
CAAAAAGAGAGTTCTTTTGTCATGTACATATGTGTAGCAGACTTAAATGTTAAACATTCAAGAATACATT
CCTCGATCCACATTAAAATTTTGCAAAGAGTAGCACAGACGGTGGCAATTGCTAAACTTATATCTAGAAA
CACAATTATGTGTGGTGATATTTAATTACACATTTATACCAGGACATATGACAATATGGAAACCAAACAT
GTTGTATCCACATGCTCTAAGGAAAACTAAATGGAGTGTGATAAAACCAAAGAAAATGTGAATATGAAAT
ATTTTTCCAACTCTGCATCTTAAAACGGTTTCTTTCATGTGTCATATCTGCTATGAGGACTTTCTTCTGC
CCATGTCCAACTCCAGAGCATGCCACAGCAGGAAGACCTACAGGTATTACTTCTCTGCACCCAGGAAAAC
CACCTCTGTCCTGACCCTGCAGCTCTCAGAAGAGCCCAGACCTTCATTCTCAGGCCCTCATCCAGTAATC
AGCACTGAATACAGAGCACTCACCATGGACTTTGGGCTCAGCTTGGTTTTCCTTGTCCTTATTTTAAAAG
GTAATTCATAGAGATAAGATTCTATCTGTTTTGTGTACATGAGAAACAGAAAAATTGTATTGTTTCTCTA
TTTTGTTTTGTTTTGTTAGTGACAGTTTCTGACTCAAGATTCTCTGTTTGAAGGTACCCAGTGTGAGGTG
AAGCTGGTGAAGTCTAAGGGGAGGCATAGTGCAGCCTAGAAGGTCCATGATACTCTACTGTGCAGCCTCG
GATTCACTGTAAGTGACGACTGGTTTGTCCGTGTTTGCCAGGCTCCAAAGAAGGGGCTGCAGTGGGGGAT
GGGAATAATTTTTCATGGTTGTGGTAGCCCCTCTTATGCAGACACCTTGAAGAAGTGGGTTGGACGTAAC
ATATTCAGAATCAATATTTAAAGATTCTAATCCTTGAAGATATCACTTTTGACCAAGTATATATGAACCA
TGTTACTGAGGTTTATGGAGGTTTGAGTATGTTAGGTCCATGGATAGGGAAAATATTAGGGGATTTTAGG
AGTAACTGAGGCTTGTTGTAGGAAGGACATCACTGTAGGGGTAGGCTCCGTGTTCCTATCTTCAAGCTCT
ACCCAGTGCAGAATAGAGCCCTCTTCTGCCGGCAAGTGGAAAGAGTTTCTCTTCCTGGCTGCCTTCAATC
CAAGTTGTAGAATATCAAATCTCCTAACACTATGACTGCGAGCATGCTGACATGCGTCCCACCATAAAAA
TAGACTGAACCTCTGAAGCTTTAAGCCAGCCTCTAGTAACTGTATTCTTTAATAAGACTGAACTTGGCTA
TGGTGTCTTTTCACAGTAAAATGGAAACATAGACAAGGTTCTAACTCTCTGTACTAGAGGACCATCTCTA
TGTCCTTGGTGTTGTATGTAAATTATTGAACAAATACTATAGACAAGTTGTATGGCCAAAAGTCCATCCC
CTTCAACAATCTACTATCTGGAACCATATAGATTAGATTCCTTTCCTGCACTCATTTCCCTTACTTGCTG
AGACATTTTGAAGACATGCTCAGAATCCCTGAACTTCCTGCTGAAAAAAAAATACCCCTCCAATTTGAAG
ACAGTTCTCTTCCAAAATTCATCATAAATACTGATCCACATGTCCAGGCATATCATGTAGTTTTAAAAAA
CAAACCAATCAATGCTAAAGTGGGTAAGTGCCTACATCATTGGTTTATGTCTGTTCATAACCTGGTATAT
AGCTAGAGACCAGGACTGCATGTTTCTCCTAGGCCACACCTCTCCCACAAATGCTGGCTCTGCCTCTCCA
GAATTCCAAGATCATGGATCTCTGGGTCCCCAAGGAACAATAAGTGTGCACTCTTGCCAGCCTGTACACT
ACTGCACTAGCTTCTCCCCCTGGAGCTTGGTCATTGCTCAATCTTCCCTTTCCAAAGCCTGGCCAAATTC
CTCCTACCTTTTGTTCTTTCAGTCAGGCCACCTAAGTCATCTTGAATGAAAAACAACACAAAATCTGAAC
TTAAAATCAACAAATAATACAAGTGCTGCGCACAAAATCAATCATTCTAAACTCATCAACTATTTTATGA
TGGAAATCTTCCAACATACAAGCTACCACCAGGTCTAAGAATTACTCATCTACATGTTGCTTCCTCTCAC
TCACAGCCTAACCATAAAAGGGCTGTTTCTTCCTCCCATGTCCCCTCTTTTGCCTTCAGAAGCAGAAGCT
CCACCTCCTCCTCTTTGCCCAGCAATTGGCTTCTTGTCGTCTTTATTATCATATTAATTACTTAGGGGAA
AATCCCGTGTAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGG
AAGGCTCACCAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAG
CCATAGGGGCTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACG
CCTTTCATCTGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAA
TATAAGGACATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTG
AGTAACTGCTAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGA
CTCTAAGTCATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTG
ACTAATACAGAAGTTGGTACCAGGAGTGGTTCTAGAGTAACAGAAGTACAAGGATGAATCTTTTAAAATA
CTGGAATTGGCTTGTTGATCCACCAGCACTTTCAACTATTGAAACCTCTCCAGATTCTCTCCCTCCTGGG
AGCTCAGAGAATTTTGAAGACCCATGGTTGAAACTATATTCCGAACTTAAAGAAGCAAATGCCCTTGATT
TTCTTAATGAATTAGGTGATTCAGTGCACAAAGCTTTCTACAAGATGGGGAAAAAATTGGAAAATGATTT
TACTGGCTGGCTGCTCTTAGTATCTGTGGAAAAAATGATGAATGAAAGGAAGGAGTTGTGTGATAAAATC
GAAAGGCTCCAGACACAAGTAAACGATCTAAAAGTTGCTAAGTGTGTCCTTGAGGAGAATCTTCTCTCTT
GTAGCAATAGAGCTCAAGTTGCAGAAAATCAAACAGAAACTCTCATTGTAAGGTTGGCTGAACTACAGCG
AAAATTCAAGTCTCAGCCTCAGAGTGTGTCAACAGTTAAAGTAAGGGCTCTAATTGGCAAAGAATGGGAT
CCTACAACATGGGACGGGGATGTGTGGGAAGACCATGTTGAAGCTGAGAATTTTGAATCTTCAGATTCTC
AAGGGTTTGCCCCACCTGAGGAAGTAGTACCCTCAGCCCCACCCCTTGAAATAATGCCTTCCCCACATGA
GGAAATTAATTTTGCAGAGTCTGATAAACCAGCAATGATTTTCACTACTGATGTTTCTCAAGGCCCACCA
ATAGTTTCTTCTAGACCTGTAACCAGACTCAAAGCAAAACAGGCTCCTAGAGGGGAGGTAGAAAGTGTAG
TCCATGAGGAAATTCGCTACACTACTAAGGAGCTTAATGAGTTTGCTAATTCATTCAAGCAGAAACCTGG
TGAATATGTGTGGGAATGGATTTTAAGGGTGTGGGATAAGGGTGGAAGGAACATAAGACTAGAGCAGGCT
GAGTTTATTGACATGGGTCCTCTGAGTAGAGATTCTAGGTTTAATACGGAAGCTCGCATAATTAAAAAAG
GTGTCAAAAGTTTGTTTGAATGGTTGGCTGAGGTGTTTATCAAAAGATGGCCTACTGGAAATGACTTGGA
GATGCCTGATATTCCGTGGCTTAGTGTTGATGAAGGGATTTTAAGACTTAGGGAAATTGCAATGCTAGAG
TGGATATATTGTGTAAAGCATAATTGTCCACAATGGGAAGGTCCAGAAGATATGCCTTTCACTAGCTCTA
TAAGACGCAAATTGGTGAGAGGGGCACCAGCACATTTGAAGGGTTTTGTTCTTTCCCTTTTCCTTGTACC
AGATCTTAGCATTGGAGATGCTTCTGCTCAATTAGATGAATTAAATTCACTGGGTTTAGTTGGATTCCGA
GGTAACAAGGGCCAGGTGGCAGCATTGAATCGCCGGAGACAAGGTGATTCTAGTTATTATAATGGACAGC
GTAGACAAAAGAATGTTTATAATAACATACCCAGCAATGGTCAGCACAGGAGAGGTGAAATTTATAATGG
CATGACTCGGTTGGACCTTTGGTACTGGCTAACCAATCATGGTGTTTCCAGGAATGAAATACATAGGAAG
CCTACTGCATATTTGTTTGATCTGTATAAGCAGAAAAATTCTCAAACAAATGAAAGAAAGGCTACATTAG
ATCATGGTAAACAGCAATCTCGGCCAGTGAATCAATTTCCAGACTTGAGACAGTTTGCAGATCCAGAACC
CCTTGAATGAAGGGGTGGCCAGGTTCCGCTGAGGAAGGATCTTGATAAGACACCCAAAGGTTTTGCTGTT
ACCCTTTCTCCAGTTCTTCCCCAGAGGGACCTAAGGCCTTTTACAAGGGTAACTGTACACTGGGGAAAAG
GAAATAATCAGACTTTTCAGGGTCTGCTGGATACTGGTTCTGAGTTGACACTGATTCCAGGGGATCCCAA
GAAACATTGTGGCCCTCCAGTTAAAGTAGAGGCTTATGGAGGGCAGGTGATTAATGGAGTTTTGACTGAT
GTCCGACTCACAATAGGTCCAGTAGGTCCCCAGACACATCCTGTGGTGATTTCCCCAGTTCCAGAATGTA
TAATTGGGATAGATATACTCAGAAATTGGCAGAATTCTCATATTGGTTCCCTGAACTGTAGAGTGAGGGC
TATTATGGTTGGAAAGGCCAAATGGAAACCTTTAGAGTTGCCTCTGCCAAAGAAAATAGTGAATCAAAAA
CAGTATCGTATTCCTGGAGGCATTGCAGAAATTACTGCCACTATCAAGGACTTGAAAGATGCAGGGGTGG
TGGTTCCCACCACATCTCCGTTTAACTCTCCTATCTGGCCAGTGCAGAAAACAGATGGATCATGGAGAAT
GACAGTTGATTATCGAAAACTAAATCAGGTAGTAACTCCAATTGCAGCTGCTGTACCAGATGTAGTTTCA
TTACTTGAGCAAATTAACACATCTCCTGGCACCTGGTATGCGGCTATTGATCTGGCAAATGCCTTCTTCT
CAGTACCTGTCCATAAGGACCACCAGAAGCAATTTGCTTTCAGTTGGCAAGGCCAACAGTATACTTTCAC
AGTTTTGCCTCAAGGATATATTAACTCTCCTGCCCTGTGTCATAATTTAGTTAGAAGGGATCTTGATCGT
TTGGATCTTCCACAAAATATCACATTGGTGCACTATATTGATGACATTATGCTGATTGGACCAAGTGAGC
AGGAAGTAGCAACCACTTTGGACTCATTGGTAACACATATGCGTATCAGAGGATGGGAAATAAATCCAAC
CAAAATTCAAGGACCATCTACCTCAGTGAAATTCTTAGGAGTCCAGTGGTGTGGAGCATGCAGAGATATT
CCTTCTAAGGTGAAAGATAAGTTATTGCACCTGGCCCCTCCTACAACCAAGAAAGAAGCACAACGTTTAG
TGGGTCTATTTGGATTCTGGAGACAACACATCCCTCACTTGGGTGTGTTACTTAGGCCTATTTACCAAGT
GACTCGGAAAGCTGCTAGCTTTGTGTGGGGCCTGGAACAGGAGAAGGCCCTTCAACAGGTCCAGGCTGCT
GTGCAGGCTGCACTACCACTTGGACCATATGACCCAGCAGACCCGATGGTACTTGAGGTGTCTGTGGCTG
ATAGAGATGCTGTTTGGAGCCTCTGGCAGGCCCCTGTAGGTGAATCACAGAAAAGACCTTTGGGATTTTG
GAGCAAAGCTCTACCATCATCTGCAGACAACTATTCTCCCTTTGAAAAACAGCTCTTGGCCTGCTATTGG
GCCTTAGTGGAAACTGAACGTTTGACAATAGGACACCAAGTTACTATGCGACCTGAACTACCCATCATGA
GCTGGGTACTATCAGACCCTGCAAGTCATAAAGTGGGACGCGCACAGCAGCAGTCTGTTATCAAATGGAA
GTGGTATATACGTGATCGGGCCAGAGCAGGTCCTGAAGGCACAAGCAAGTTACATGAAGAAGTTGCTCAA
ATGCCTATGGTTTCTACTCCTGTTACACTGCCATCTGCTGCCAAACATGTGCCTATAGCCTCATGGGGTG
TTCCCTATGATCGACTGACCGAAGAGGAAAAGACTAGAGCCTGGTTTACTGATGGCTCTGCACGTTATGC
AGGCACCACCCAGAAGTGGACAGACAGCTGCAGCATTACAACCCCTTTCTGGGACAACCCTGAAAGACAC
AGGTGAAGGGAAATCTTCACAGTGGGCAGAACTTCGGGCAGTACACATGGTATTACAGTTTGTTTGCAAG
AAGAAATGGCCAGATGTACGATTATTCACTGACTCATGGGCTGTAGCCAATGGATTGGCTGGATGGTCAG
GGACTTGGAAAGATCACAATTGGAAAATTGGTGAGAAAGACATCTGGGGAAGAAGTATGTGGATAGATCT
CTCCAAATGGGCAAAGGATGTGAAGATATTTGTGTCCCATGTAAATGCTCACCAAAAGGTGACTTCAGCT
GAGGAGGAGTTCAATAATCAAGTGGATAAGATGACCCGTTCTGTGGACAGTCAGCCTCTCTCCCCAGCCA
TCCCTGTCATTGCTCAATGGGCACATGAACAAAGTGGCCATGGTGGTCGAGATGGAGGTTATGCTTGGGC
TCAGCAACACGGGCTTCCACTCACCAAGGCTGACCTGGCTACAGCTGCTGCTGATTGCCAGATCTGCCAA
CAGCAGAAACCAACACTGAGTCCCAGATATGGCACCATTCCTCGAGGTGACCAGCCAGCAACCTGGTGGC
AGGTTGACTACATTGGACCACTTCCTTCGTGGAAAGGACAGCGTTTTGTTCTTACTGGAGTAGATACTTA
TTCTGGTTATGGATTTGCCTTTCCTGTACGTAATGCCTCTGCTAAAACCACCATTAACGGACTGACAGAA
TGCCTTATCTATCGTCATGGTATTCCACACAGTATTGCTTCTGACCAAGGAACTCATTTCACAGCCAGAG
AAGTACGACAGTGGGCCCACGATCATGGAATTCACTGGTCTTACCACATTCCCCATCATCCTGAAGCAGC
TGGTCTGATAGAAAGATGGAATGGCCTTCTGAAGACGCAGTTACAGCGCCAATTAGGTGGTAACAGCTTG
GAAGGCTGGGGTAGAGTTCTTCAGAAGGCAGTATATGCTTTGAATCAGCGCTCGATATATAGTACAGTTT
CACCCATAGCCAGGATTCATGGGTCCAGGAATCAAGGGGTGGAAAAAGGAATAGTTCCACTTACTATCAC
TCCTAGTGACCCTCTAGGAAAATTTTTGCTTCCTGTCCCCATAACTCTAGGTTCTGCTGGCTTAGAAGTT
TTGGCTCCAGAGAGGGGAGTGCTCCTACCAGGAGCTACAACAAACATTCCATTGAACTGGAAGCTCAGAC
TTCCCCCTGGTCATTTTGGGCTTCTAATGCCCTTAAACCAACAGGCTAAAAAAGGAGTAACAGTGTTAGG
AGGGGTGATAGATCCAGATTACCATGGGGAAATTGGATTACCTCTTCACAATGGTGGTAAGCAAGATTAT
GTCTGGAGTGTAGGAGATCCCTTAGGGCGTCTCTTAGTACTACCATGTCCTGTGATTAAAGTCAATGGGA
AACTACAACAGCCTAATCCAAGCAGGATGACAAAGGACACAGACCCATCAGGAATGAAGGTATGGGTCAA
TCCTCCAGGAAAAGAGCCAAGACCTGCTGAGGTGCTGACTGAAGGAGAAGGAAATATAGAATGGGTAGTA
GAGGAAGGTAGTTATAAATACCAATTAAGGCCACGTAACCAGTTGCAGAAACGAGGATTATAAAGTAATA
TGAATGCCCATTGTAAATTTACTAATGCGTTTGCGATTGTACGAGGGATAGTTATATCATGTTAGGCGTA
TTTACAAACTTGTTATTGTTTTATGTGAACATGAGATATTATTTGTGTCAAGTTGACAAGGGGTGGATTG
TAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGGAAGGCTCAC
CAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAGCCATAGTGG
CTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACGCCTTTCATC
TGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAATATAAGGAC
ATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTGAGTAACTAC
TAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGACTCTAAGTC
ATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTGACTAATACA
TCCCTACATACAGGAAACTTGATGTATAAGTAAAGAAAATAGTAAATCTAAAAATTTCCTTATCAAATAC
ATGCAAGAAATCCAAAATACCATGAAAAGACCTGATCTAAAAATAGTAGGAACTGAAGGTGAAGTGTCCC
AGCTCTGAAAACTAGAAAATGTTTTCAATATTTTTCCTAACAGTGAAGACATGGATCTAATGAGGCCACC
TCTTATAGCCATGCAAGACTGACAGTGGAGGGATAAGGACACCAATCCACCCACAAAACTTTTGACCCTA
AATCAGTTTTATCTAAAAGCAATGCAGGGGCACAAATGGAGCAGAGACTGGAGGAATGGTCAAACAATAA
CCTGTCATATCTGAGACCCACCTAATTGGCATACACCAGTCACTGACATTATTAATAATGTTCCATTATG
CTTACAGGCATTTCTCTAGCATTACTATTCTTGGAGAGACTTCACACAGCATCTTATTGAAACAGATGCA
GACACCCAGAACCAAACATTGGATGGAGATTGGGATCCTTAAAGAAGAGTTGGGAGGATAATTGAGAGAC
CTCAAAGGAATAGCAACCCCATAGAAAGACACGAACAGGGTCAGTAAACCTGGACCCATGGGGTATCTCA
GAGACTGATCACCAACCAAAAATCACAGAGGGCCTGGATTGATTCCCCTGGCACACATGTAGCAGAGGTC
TGCCTTGTCCTTCAGTAGGTGAAGATGAGCCTAAGGCTTCAGAGACTTGATATATCAGCATACAGCAACA
CCCAAGTGTGTCCCACTATCTCAGAGGTGAAGGGGTGGAGATGGGCAGAAGGGTCCTGATAGGGGACAAC
TGCAAAGAGGCAATATTTGGGACAGAAAGAAAGGAAGAGAGAGGAAGATAAAGAGAGAGATGAAGGAAGG
AAACAAACAAACCAAGATGAAGAGAGAGAAAAGGGGGAAAATAGCCTTGAATGGTTCAGGGATTCAAAGG
GACATACCTAAGCATGGTAAAACAATGCACATAATGGCAGCAAGTAGCTAACACTGAATTAAATAGAAAG
ACACATAAAGCAGTTCTACTAAAGTAAGAGACAGAGTTGCCCAATCTCACCCTATTTATTCAATAATAAT
GTACTTGAAGTTCTAGCTAGGGCTGTAAGACAACTCAAGGAGATCGGAGGATACAAATTAGAAAGAAAAA
TTCAAAGAATTGTAATTGGTAGATGATAGGATAATATACATAAATGACCTCAAAATTCTTCCAGAGAACT
CTGAAAGCTGATAAATACCTTCAGCAAAGTGGCTAGAAACAAAATTACTTCATAGAATTCAGGAGCTATC
CTTTATAGAAAAGTTAAAGTGGCTGAGAAAGAAATTAGGAAAATCACATTCTTTGCAATAACCAAAAATA
ATATGAATTAGCTTGGTGTGACTCTAATCTTGCAAGTGAAAGATGTGTGTGACAAGAGCTTCAGGACCCT
GAAGAAAGAAATCAAAGAACTCAAAGATGCAAAGTACTCTAATGCTCATGGATAGGCAGAATTAACATAA
TGAAAATGCCAAATTTAACAATTCAATCTACAGATTCAGTGGAATTCCCATTAAATATCCAACCCAATTT
ATTACATTCTTGAAAAAGCAAATCTCAACTTCATATAGAAAAACAAGAAATTGAGGGTAGCTAACAAAAT
CCTGAACAATGAAAACACTTCAGGAGAATTCACCATCCCCTACCTCAAGCTGTATTTTAGAGCAATAGTT
ATTAAAACTGCATGGTATTTGTATAGAAACAGATATGATGATCAATGTAATTGAATTGAATACACTGACA
TAAAACCACACTGTTATGGACACTTGATTTTTGACAAAGAACCCAATAATCATAATAAAAATCATAATAA
GAATGCATCCCCCAACAAATGGTCCTGATCTAAATGCAAATAGATTCATATCTATCATCCTGCACGAAAT
TCAAATCAAAGTGAATTGCAGACTTCGACCTAATACTGGATTAACTAAATCTAAATGAACAAAAAGTAGA
GAATAGTTTTGAACTCATTGATGCAGGATTCAATTTCCTGAACAGAACCACAATGGCTCAGGCTCTAGGA
TCATAAATTGGTAGATAGGATCTCATGAAACTGAAAAACTTCTGTAAGGCAAAGGCAATAAAACAAAATG
GCAACCTACAGATTGGAAAAAAAATAATCTTCAGTATCCCTAAATCCCATTGAAGGCCAATATGCAAAGT
ATATAAAGAACTCAAGATGTTATCCTCCACAAAACCAAATAAATCAATTAAAAATGAACTACAGAGCTAA
CAAGAGAATTCTCAACAGAGGAATCACCAATGACTGAGAATCACTTAAAGAAACATTCAATATTTGTAGT
CACCAGAGAATTGCAAATCAAAACTACCCTGAGATTCTACTTTATACCAATCATAATGGTCAAGATAAAA
ATTCAAATGACAGCGCATGTTGGTGAGGATGTGTATACTTTTGCATTGCTGGTGAGGAAAACAATCTGGC
AGCTCCTCAGAAAATTGTAAATAATTCTACCTGAAGATCCAGCCATACCACTCCTGTGCATATACATAAA
ATGTGCTCCACCATACCACTAGGAGATATGTGCCACTATGCCCATAGCAGCCTTATTTGTTAATAGCCAA
AAGATGGATACAACCCTGATGTGCCTCAAACAAAGATTGTATATAGAAAATATGGGTTCCCTTACACAAT
GGTATTCTACTCAGCAATTAAAACGTGAGAACATCATAAAGTTTTCAGGCAAACTGATCAAATGAAAAAG
TATAATCTTGAGTGAGGTAACAGAACCAAAATGACCTGCATGGGATGTACTCACTGGTAAGTGAATATTA
GACTAAAAGTATAGAATATCAATGATGAAAGCCACAGACCATAAAGAGTTTAATAAGATGGAAAGCTCAA
GTACGGATTCTTCAATCCAATATAGAAAGAGGGACAAAATAATCAGGGGAGGCAGAGGGAGAGAGAGACA
TTTGGTGGAAATGGGAGAAGAAGGGAGAAAGGCAGAAAGGATCAGGCGTTGGGGAACACTGGAAAGCAGC
CCAGGGGTCCTGGTAAATGGATTAAATATTCAGCTGAATGGAGGTGGGAGGCAGGGGGAAGCTCTGCAAA
GTCCAAGAGACCTGGGATGTGAGAGGCTCCCCAGATGATAATCTTAGCCTTCATGCCTAACAGTTGTAGA
TAAACCCTGAAGAGATCACTTCCAATAGATGCAGAGGGCCCTAAGTGGTTGGATGGAGTCCCCCAACTTA
CCTCAAAATTGTCAATACTCATAGAAATTAGGACAATGAAAATCAAAACACCCTGAGATTGTATCTTATG
TCTGTCACAATGGTTAAGACCAAAACCTCAAGTGATGGCTTGTGCTGGCAAAGATTCAGAATAGTAAAAG
TCTCCCCATGGCTTGTGGGAATGCAAACTCTTACAACCTCTTTGGAAGTATATTTGATTGTTACCTGGTA
TAAAATGGCAAAAAAAAAAAATGGTTGAAGGGGGACTAAAAAAGGAAGAAAGGGGAGAACTATGGGATGC
GAAACAAGAAAGTTTGTTGCAAAAGAAATATGTTTCCACTGCAAACCCTGAGTCTCAGACAGAAGGGGAC
CTGGAATTCTTCAGATACAAAGAATCTCTAAACCCTGAGGACATTCTATCACAAATAAGTAAAATTCAGA
AAATTCTGAGTGCTCCCATCACGGAGATGAATCTGCTATGAACAGCTCATAGGTGTGACCCTCTACAAAA
GCCATATTATTGAAAAGCCACATTGTGCCCAGACTTTGGAAAGACTGAGCTCATATCCTGAAATACAGTT
ATGTGTGGTTCTATTTAATTACACATTTACACTAAGAAAACATGGCAGTATGGGAATGAAGCTTGTTCTG
TACACATTAACAGAGGGAAACTAAACAAAGTATGGTGAATCCCTAACCAAAAGTAAAAAAAAAAAAAGAA
AGAAAAGAAAATAAAAGTGAAACTACAATATGTTTCAAATGCTGTAACTGAAATCTGGTTTTTTGATGCT
TATATCTGGTATCATCAGTGACTTCAGATTTAGTCCAACTCCAGAGCATGGTATAGCAGAAAGACATGCA
AATAAGCCTTCTCTCTGCCCATGAAAAACACCTCGGCCCTGACCCTGCAGCTCTGACAGAGGAGGCCAGT
CCTGGATTCGATTCCCAGTTCCTCACATTCAGTGATCAGCACTGAACACGGACCCCTCACCATGAACTTG
GGGCTCAGCTTGATTTTCCTTGTCCTTGTTTTAAAAGGTAATTTATTGAGAAGAGATGACATCTGTTGTA
TGCTCATGAGACAGAAAAATTGTTTGTTTTGTTAGTGACAGTTTTCCAACCAGTATTCTCTGTTTGCAGG
TGTCCAGTGTGAAGTGAAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCTGAAACTC
TCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTGGGTTCGCCAGACTCCAGAGAAGA
GGCTGGAGTGGGTCGCATACATTAGTAATGGTGGTGGTAGCACCTATTATCCAGACACTGTAAAGGGCCG
ATTCACCATCTCCAGAGACAATGCCAAGAACACCCTGTACCTGCAAATGAGCCGTCTGAAGTCTGAGGAC
ACAGCCATGTATTACTGTGCAAGACACACAATGAGGAAATGTTACTGTGAGCTCAAACTAAAACCTCCTG
CAGAGCACCCAGGACCAGCAGGGGGCGCAGAGAGCACATGGAGTTCTGATTCACAGAAGAGTTACAGCCT
GTACAATTAGACCCAATCTTCAACAAACCGTCAAAATATTCGATCCAAAATTGTTCCTGTCTAAAAGTAA
TTCAAGGACAAAATGGACCAGAGACTGAAGAAATGGCTGACCTGTGACCCTCCCAACTTTGGATCTATCT
CATAGGCAGGTACCAAACCTTGACATTTGTCACTGACACTGTATTGTGCTTGCAGACAGGAGCATAGCAT
GGCTGACCTCTAAGAGGCTCTGCAAGCACCTGAATGAGACAGATGTAAATAGAGTGTACAACTGGATTAA
GTTTGAAGACTGCAATGGAAGAGTTAGAGGAAGGAATGAAAAATCTGAAGGGGATCACAACCCCAGAAGA
AGACCAACAGTGCCAATTAAACTGGATGCCTGGGAACTCCCAGAGACTAAGCCACAAACCAAGAATCATG
CAGGCTGGTCTGAGAATCCTGGCACCCAAGTCTCAAGGAACTGCCTTTTCTTGGCTCAGATGGGAGAAGA
TGAGCCTAAAGCTTTAGACTTGACGCCCCAGGGATGGGCAATACAAAGTTGAGTTTCTTGGGAAAGTGAA
GAGGATGGTGGGAGGAGGAATAAATCTGGGAAGTGGGACTGGTTGGGGACAACATATTGGTCCTAAATTT
ATGAAATAATTATCTAATTGATAAAAAGAGTCCTTGGGGTAATGGAGGGCTAGACTCCTCTGTGCCTAGT
TTGTAACTCTACAGGGATCCTCTTTAAAAGAATAGGGTGCACATAGAGTATATGTGTGTGACACTAATAC
AGGGGTAAGTGTTTCTGTAAGAACTTTATGAATAAACTTTATTAAAACATCAAAAAGTATAGGTTGTAGC
AACCCTTGACCTGTACGAATGTTTATAAAACTTTCTATTTTCCTTAATTATATCTGTTTTGCATTTGTTT
ATTTATTTATTTACTTACTTACTTATTTATGATTTCACTGTGTCTTTCTGTAGTCCTGTATGTGTTTATT
TGTCTCTTTATTGCTCTGTTTCTGTTTCTTTCTCTCTGTCTAGTATTGTATCTCTCTGTGTCTCTATGTC
GCCGATTGTGTCTGTGTGTATGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGCATATTGAAA
TGAGATCTCTTCTTCTATCAGTGTACATAATGACTTTGAAATAAAGTCCATCACTGGGCTTGGATATCAC
TATCTTGTTAGAATGGTTGCCCAAAGTGTTCCAACCATCACACTGTTTCTACATATAATAGATGGGTTTA
TTGATTTACTACCAAAACTACCCCATCTTAAGTTATGGATATTAAACACAGATCCTCATGGTGTGTTAAG
AACTTGAAGCACAGAGCTATATGTACAGCCCACTAAAAATGACTTAAATATAAGATAAACTCTGGCTTGA
ACAAAACACAGAGCATCACACGAGGCAGAAGTGAATCTCTATGAGGACCAGGATCACATCCCAAAGAACC
AAAGAACACTTGAGACTGTGGAACCCTAGAGTCAGGGCTGACACTCAGTAAGATTTACTTCATAGAGCAT
GATGTGGGATTCAAGAAGAAATCAGGCAGGGCCTGTGACCCATGAACCAGATGACTTCCAGTCTCTCCAT
CATCCTCACACAAACCATAGGCAACAGCTCAGCACTGACTCACCTGTGATGCTGGTGACAAAATGTGTGC
AAAGCCTCAGAACTGAGACGTGAGGCCAATGTTGCTACCGACACTCAGTGAGCTTCAATTTGCTGCAAAC
TGCTCCAAAACAACTCAAAGGGTAACTTCTTCTTTTTCTATTTGTACTTGTGATGCCTTGGTAGATATAG
TTCCCCAATAATTTAATAGGACAAATCATTTTTCCTTTTAACACATTAATCCCCTTTCCTTCCCCCAAGA
TTCTAAAATTTTTCTTTAACACTGATGTCTGAGAGATATGGCATAATAGATGTTTGTCTTATTCTGAGTT
GTTCCTTATCAAAAGAAATCAGCTGTGGCACTTTGAACCTAAATATAACAATATTTCACAAAGGCATTCT
GGGAATATATAGATGGTATTGCTACAAAAGAATAGGAGGATCTATGGCCATACCACCCTTAATGAACCAG
ATACTATCTAAAAGATTAGGACAGCTGGGCATGTTGGCACAGGCCTTTAATCCCAGCACTAAGGAGGCAG
AGGCAGGCAGATTTCTGATTCGAGGCCAGACTGGACTACAAAGTGAGTTCCAAGACAACCAGGGCTATAC
AGAGAAACCCTGTCTCGAAAAAACAAAACAAAACAAAACAAGAGTAGGAGGGTATTAGATGCGAGGTGAT
GATGGCCATTCAATCAAACCAGAATGTGACCTGAGAAAAGGTCTAAGTTTGTCAGCTTGTCCTGGAGATG
TGTTGCCTCTGATAAATGCAGAGCTGGAACTGCAATACATTGGATTCCTGTGAGTTACGGAGAAATAAAA
GGAATAGCCTCTGTTTCCTTTGGTTCATCAAGTTGGCAGTGAGCTAGAAGATGATACTGGGAACCATCAC
ATGTACTTCTACAGAGTTATTCTACATTCTACAAGTCAGTCTTGCTTGCTTTCGTTTCTGTGAGGAGCTA
AATACAGAATGTTTTCAATGTCTCATAATGTTCTGTGCACACCCATGGGTGCCTAGCCAAGGATAGAAAC
TTGTATCTGATAAGGAAAGAGGATGCTGCAGTGGCCACACTCTGAGATCACCTCCTGCCAAATTATACTA
GAGTGTTTTACATAGTCTTGAAAACACTAGGTCAAATATGTTGTCATCCAGATATGAAAACTCTGTGCAA
CAATTCAGAAATACAGTGGTCAGGACAACTGGTATGTAACACTTTAGTTCCAGCCCACATTAATCTCACA
TCTTTTCTGTGGTTTCAATAAAGAGCACACATGTTTGGAACACCATCTCCACTTTGTATGCTTATCCTTA
TGCATCAAACTTTTCCTGTAATTTCCTACCCCGCACAGGTTCCTGTCTTGATCTCTTTTTCTAATGAACA
GCAATACAGAAGTGTTGGCCAAATGAACACTTTCACCCCAAGTTGCTTTGCCATTGTGTTTCATCACAGC
ATTAGTAACTCCCAGTAAGGCTACTGGTTACCCTGCATCTTCTATGTAGATCTTTTGATGAAGTTCCAGG
CTTGGGGTCTTTATCTGACTGTTATCCTGGTTAATTCATGTCCACCAATAGAATATTGTTCTCATTTTCA
ATATCATATGAAGTTACCTGTTTATAGGATCTTCCTAAAGCAGAAAACTATATAAAATGTCTGCTTACTT
TAAGAAAAGTATGTGTCCTTGGAGGTAAATGGAGGAAAGGGTGGAGGATGTTGAGTAATGGAAGACTGGC
TAATACAGGAAGGTCACAGAATTGAATGATTTTAAAAATTTTAACTCCTCATCAATGAGGTACTTCAAGT
TGAGGCAGGAGTCCTTGATGCACAGGTGACCCAAAGGCCCCAGCCTCTGTTTCTTGGTCTGCTCCAGTCT
CCCGGCTCAGCACAGTTCACTGAGTGACAATCTTTAAGATAGTCTTTCAGGATACAGTTATCACAGTTTT
CAAACTCTCTTCATTGAAACAATATAATGAGTCAGAGTCCAGTGTGCCATTAATAGGCCCTATGCAATAG
GATTTTACTTCATCTGTGGAAAGAAACCACCATGGCCTCATCAAGGCCTCATTTGATGATTAGTGTAGAA
AGCGTCCCCAGAGCTTTGCTGGGATGAAAACCCTGGCAAGATGTTTAGGGCACTCTCCATCTGACAGGAC
AATTCTATCAAGGGTTGCTTCCATATAGAGAGAAATCTCCACATCTGCAGTATTTCCCGATTTATCAACA
GTTCTTTACCCCGTGTCATATGCATAAAATCTTTTCTCTGTAGAATTTTCAGTACTAAAAACTAACAAGG
ATGTTGGTCCTGATATCAGACATAATAAATAAATAAACATCAAATTATACCCTAAACATGTGGAGATGGT
TTTCTGTTATGAATTTATTGGCTCTCTAAAAAGTGTTAATTAAGCCAGGCGTGATGGCACATGCCTTTAA
TCCCAGCACTTGTGAGGCAGAGGCAGGCGAATTTCTGAGTTTGAGGCCAAACTGATCTACAGAGTGATTT
CCAGGACAGCCAGGGTTACACAAAAAAACCCTGTCTCCAAAAAGTAACAAAAAGAAAGTGTTAATTAACA
TCTACACTTTAAGATAATTTGGTGGCAAAGGTTAATAGTCTGAAATACTAGATATGAAAGTATGACACCT
AAATTGCATGCAGAGAATAAAGCTGAATTCCAATGAGATTCATGCCTTGTGAATCCATTCCAATCTGATC
TCAATCTTCAAACATGTTTGTGCATAATTTACATCTTAATCAGTTGCTGGAAATTAAAAGGACATAAGCT
AAACTTAAAACTCTTTCTATTTAATGTGTCAGAATAGAATATGTGCACTGAAGTTTTCATGTGCATAGGA
TATCATTGTTACAATGATGGTTCAAATACGCACCAGTAGCACAGGTGATGCTTGACATGAAAAAAACTGT
GACCAGAGCCCAGACGTTGATGTTGGCTGAAAGAGCCTAGTGTCTCACATTTGATCAAGCAAAGTGTTAT
TCAGAGAAGCAGTGCCAGATTTGGGATCCTTCTTAATGGATCAAGAACATGAGGAAGATTTGGAAGCCAG
ATTGATGAGATTACTAGAATCCTGGATCTGAACACACAACACACAATAGTAAGTTGAACTTTTCCACGCA
ATGCTAAAGATAAAGCATCCAGTATCATGTTATACAGGACCAAGGTGAGGATCAGTCTGTGGGTGAAGTA
CAATGAACTGGAAATTGTTTGGATTTTAAATGTTGGTTTTTAAATTATATATAAAATATATATATATATA
TATATATATACATATATATATATATATATATATATATATATATATCGGAACCAACATTTAAAATTTGGAT
TTTAAATGTTGGTTTTTAAATTATATATAAATTATATATATATATATATATATATATATATATATATATA
TATATATATATATATCGGAACCAACATTTAAATTCCTAATTCTTAAGGACTTCACTTTTGACCAAAAATA
TTTGAAATGGGTTATTTAGGTCTGTGGTGGTTTGAATATGCATAGCCTATAGGAAGTGGAAGTATGGCCA
TTTTGTAGTATGTGTAGCCTTGATGGAGGAAGTACATCACTATATGGTGTTGTGAGAGTTGAGATCCTAT
GTTCAAGTTCTGCCAAAAACAGAAGAGAGTCCCCTCCTGGATATTTGAAACAGATGCAGAGGCCCAAAGC
CAAACATTGGGTATATCTCAGGGTTTCTTATGGAAAAGTTGGCTGAAGGATTGAAGGCCTTAAAGGGGAT
AGGAACTTCACAGGAAAACCAACAGATTCATCTAACCTAGACTCTAGGGGTCTTTCAAAGGTTGAGTCAC
CATACAAAAAGGACACAATGGCTAGACCTAGGTCCCTGATACATATGTAGCAAATGTGCAGCTTAGACTC
CATGTGGATTCCCCAACGACTAGAGCAGGTATTGTCCCTGAAGTTATTGCTTGTCTGTAGAATACATTTC
CCAACATAATTGTCTTGTCTGGCCTCAGTAGGAGAGTATGTTCCAATCCTGGAGAGACTTGATATGCCAG
GATTGAGAGATTAAGGGTCTCCCACCATCTCAAAGTTCATGGGTATGACAGGGGAGGGGCAGTGCAGGTT
TTCCCCATCTCTGATTTCCAGCATTTGCACCCCCAATATTGAGGGGGAGGTCTAGCAATTGGAGGGGGGA
CAAACAGTATGAGAAAGCTAACTTTAGTGGTGTTGTCACAGTGTGGGGTATTGTGGGTGGGAGTGGAGAT
GAATCCTCCTCCTCCTCAGGAGGCTGTAGCAGGTGCTTGCCCTCTTTTGGGACAGTAGAGCTGTGGTCAG
TACTGGCCTGTTCCTGACAAATTTATTCTGTGCTGTGACCATTTATTCAAGGGAGGAAGATTTAAGACTT
GCTATGATAACCTGACGAATCTGGACAAACAAGAGACAGGAGGTAACACCTGAGTTACTCTTTTGCTTGC
TAGTACAGAAGAGCACTATAATCCACAAATTGGGGTCCCACATATTCTTGAGTGGGATCCAAGGTGCCAT
AATTTCAGCCACATTCCAAAGTCCCTCAAGGTCTGACAGTTTAGTCTTTAGGCTTCTCCTAACCAAATCA
TATTTGGAGTTCTTTAACATAAAAGGGTAGTTTCCCCATATCACTGCCAGCAAAACAGGTTGAATTTGGA
CAGACAAGCAAAACTATCACAAACAAGACAGACTATGTGTGCGATCCAAATGTCTTGTGATTAGAGGGGA
AGTTCTGCAGCTTATTAGGCTGTGTCCTTATGCCCACAAATGTCTTCAGATAGGAAAGGGCCATTGGGTG
CCAATCCTTAGTTCTTCTGTTTCCTGGGCTGTCAGTTTTTATGTGGAGAAGACATGAACCAAATGCAAAG
TCATGTATCCTACAAGAACTGACATACACAGACAAACAAGGAATAACAATGAGCTCTCTCATTCACCTAA
GGGGGTCTTATAACATAGAACAGAAAGGGGCCAACTTAGCAAGAATTGACCAAAAGGTGGTCACCTAGAC
CACACCACAATGCAGGAAGGATATCAATGAAGGAAGAACAAAGGAAAGGCCAAATCAAGTTTGTTGGCAC
ATGACATAAAACAGTGCTCAAAAAACAATAGATGCGAGCAAAATGAAGCATTGGAATCATATCGGGGTAC
ATAGGGGTCACTCTTACCCCTGTTCAAGTGCCAGATGTTGTTTTAGCCTTAGGCTCCCTGAGTTTGTCTT
TAGGGGAAATGGGTAAGAATACACAAAAATAATGTCACAGAATCTTAGAGGCAGATGAGAAGTCAAAGCA
GACTCATTTATTGCTATAGAAAAGAATGCCTTTATACCTTCTGTCCATAACACCTCTGCCCATATATGCT
CATCTCTGTGAGGCAATGGACTACCTGCAGACAGGCTGGTATCCAGTCAAGCTGAGGTCTGAACCACAAT
GGTCGTAACTCACCTAAAGGACGTGGTAGGCATGACGCGATAGGCGTTCCCTCATGCTCCTGGAACTCCG
GCCCCTGCCTAAGGTACCACCTCCCACAGCCCCCACAAGAGAAGCATGGTCAGTAGTCATGTAAGCAATG
GCCCAAGCTTCTGACCTTCAGCCTAAACTCCTCCCCAGTTACCTAGCAACAGTGAAGACCATAAAATGGG
ATGTTAGGCCCCCACCTCACTCTCTTACTCCTTTGTTCCTTTACCTCTCACTTCTCTCAATTCTCTCTCC
TCTTCCCTTTCTTTGTCTTCTTCTTTCCTTGTCTCTCTGTCTTTCTCTTTCTCTCTAGCCTTCTCTGCCT
CTCTCTCTCTCTCTGTCTCTCTGTCTCTCTCTTCTCTCTTTCCCTTGAATTTCTTTTTTTCTTTTTTCTT
TTTTTGATGAGCACAGTATAAATAGTTTATTGCATTGTTTCTGAATGTGGCTGTATTCTCTATTGTTCTC
TTTCTTATTTTTTTTCTTTTTTTGGTTGTTTTTGTTTTTATAGTCTCGCACAGAATTCTACATCTACCAA
ATCCCCATTGTGTACTTTAGTTTTGTCTTGTATTCAAAGGTTCTTTCAGAAAGAATCTTAAAGATGAAAT
TTGCCTTCCAACTTTTCAAAAATACATATAAAGATAGATGTTACATAGTTCACGGAATAGACACATATAC
GGAGATGCAGCAATATCTCCTTTGTGCCTCTTGTATATTCATGTTATTTCCTCAACTAAAAATACATAGC
CACAAAGACATACAATGAGCACTCCACTTAGGAAAATATGGCCATATTTTTTTACATTTTTATGATTTTA
TGATTAGGTATATTCTTCATTTACATTTCCAATGCTACCCCAAAAGTCCCCCAACCCTTCCCTCACTCCC
CTTCCCCACTCCCACTTGTTGGCCCTGGAGTTCCCCTGTACTGAGGCATATAAAGTTTGCAAGACCAATG
GGCCTCTCTTTCCACTGATGGCCCACAAGGTCATCTTCTGATACATATGCAGCTAGATACATATACATAC
ACGAGCTCCAGGGGGTACTGGTTAGTTCATATTGTTGTTCCACCTATAGGGTTGCAGATCCCTTCAGCTC
CTTGGGTACTTTCTCTAGCTCCTCCATTGAGGGCCCTGTGATCCATCCAATAGCTGACTGTGAGCATCCA
CTTCTGTGTTTGCTAGGCCCCATTATAGCCTTGCAAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTT
GCTAGTGTGTGCAATGGTGTCAGCATTTGGGGGCTGATTATGGCATGGATCCCCGGATATGGCAGTCTCT
AGATGGTCCATCCTTTCATCTCAGCTCCAATCTTTGTCTCTGTAACTCTTTCCATGGGTGTTTTGTTCCC
AATTCTAAGAAGGAGCAAAGTGTCCACACATTTGTATTCATTACTCTTGAGTTTCATGTGTTTCCCTTGC
ATTTCTATAATAAACCATAAGGAGTCTCTGCTCTACCAAGACCCGCTGCACACTCTGGTCAGTGTTGGGA
ACTTTTCCCCTATTCCCTCTCTCCTATAACTCCGGGGCTACAGGGTGTCTCCTTTGGGTCCCGGTTGGGA
GCTGTCTCTTCTCAACCCCCTGACTCATGGGTCAGAGGCCTAAATCTCCACCCAAGGCTGTGTGAAAAGC
ACCGGGTGGTCTCCCCATATCTCCCTGTCCAGAGCACAGGAACTCTGGCCGGACATGGCATATTTTTCCT
CCCCAACTTCTTCCCCGGCCTCCTCAGGGCTGTCCCTTCATTTTGTTCCCCACACATCTCCACATGGCTG
CCACCATCCAATTGGCTGCTGAGGTCACACACTCTGTCTTTGTTCTTCTCTGAGTCTCATGCAGGTTTTG
TGTTAGTAAATGCAAAAGTGCCTGCTGTGCATGCATGAACCATTACAGGCTGCTAGGCAGAACATGCTGA
CTTGCTCCTGGATTATAAATCCATCACTGTGATAGCAGGACATATCCAGAAGACATTATTTAACAACACT
CCTCTTCGTGCTCAACCTCTCATGGTCTTTCTACCTCCTCTTTCTTAGTGTTCTCTGAGCCTACATGAAA
TGTGAACAAACCTGAAAAAAATCTCTGTGTCAAATACATAGTGTGGATTGGGAAGGAAAAACCCTGCACT
TGTGTGTGGGCAGGGAAATGCTGGTGCTTTAACAGGACAAGTGCGGTGTGGCTAGAGAAAGTGATGAGAA
GAAGGGAAGCATGAGAACTGGGTGGGTGGATCCCATGTCTACTGAAAATGCTATGTTGATGTCAAGATAT
TGTGTCTTGTTACAAAAATTCATTGAGTACCTAGGTTATTCTCAGTATATAAAAGGGGAGGAATGAAACT
AGAATTAAACACACACACACACACACACACACACACACACAAACACACACACACGAGTAGAGAAAAGAAA
TAGTCATGAGTTGCCTAGTGAATGAAGAGCGGAAAATGGTGCAGTTAATAGGGATCATAGAAAGAACTGG
GGGATGCACACGAATGGGTTTCCTGTAATTATGTCTTCATAGTAATCTCTGCTCAATAATCAGACAGTGA
CAATGTATGCCTCATTTACAAGCCCTGATGGCCTCTCAGAGGAAAGCATCTCTCTGAAATGAATAAAGTT
CAGAAATGTCCTAAGTGTCCCTGTCACAGGAAAGCAGTGTTGGTAACGTTTCCAGGAAGCTCAGTCTTTG
TCAAATATCCACAACAAGAAGAAGCCATGTCTAGACAGACAACAGACTGGGAAAGACTGAGCTCATGTAT
GGAAACACAACTATGTGTCATGCTTTTATTTTCACATTATACTGAGGGGATATGACATTATAGAAACACA
GTTTGTTCTTTGCATATGCTGAGAGAGGAACTAGATGAAGTGTGCTAATTCTTAGCAATAAAAAGATATA
CAAAGTGGTACTTTACTGTTTCAATTTTTGTAACTGGCATCATTGTCTTTGATATTTTATATCTTCCTTG
AGCACTGCCTTCTCTCAAGTGTCCAACTTCAGAGTATGCTATAGCAGGAAGACTACCAAATAAGATTAAT
TTTTTTGTACCCATGAAAAAATTATGTGCCCTGACCCCTGTTCTCTGAAAGAGGAGCCAAGTTCTGGATT
CCCAGATCCTCATATTCATTGATCAGCAGTGAACACAGATCATTCACCATGGACATGGGGCTCATCTGGA
TTCTCCTTATTGTTTTTAAAAAAGGATTTCATTGGGAAAAGCTGCCTCATATTTCTATGACCAGGAGAGG
AAGATACAGCTAGAGACACAAGCCCCACCATGTAAAATCTGTATGGTACTCTCGTTTTCATTTTACAACA
TTTTGCTTTTGCATTGCAAAGGAGCAATAAGGGTTCAGCAATCAGCACTGTAACTGTACTTTTAAAATTT
CCACCTCTACCCTCTGTGTCCTCTATCTAGTGATAGAAAGTGAAATAAGCACATAAAGCATGGGACAAGA
AGAACACACAGAGGAGCAGAGACTGGCTACAAGTGGCAGCCAGCATGGAGCTGGACAGAATTTAAAAAGA
TAAAGAGAAATGTCATGGCATGAAGCAGTGACTTTTTCTGTTCACAATGCCTGCAAAAACTTTATGGAGC
CTACTACTGCTGAGATATGCAGGTTTGGTTCCAGAGAGGATTTTCTGTTTTATTTAATTTGCTTTTAAAT
TTTTCTTCTTTGTATAGTCTGTATTTTTAAAAAGGGGTTGAATGAATACCTAAGCAGTTGGAAAATTTGT
GAGTAGAAACCGAGGGCCTGAGAAACAAATAAATCAAAATTTTGAAATGGCAAAAGAAAGGGTTCATTCT
ATTTTCTCTTTTCAGAAAAGGTTGCAAAGTTGGATGTGCAAATGGAGATGTTATGGGTGGACTTGGAACA
TCTTGGGAAGGAAGGAACCCAGGAAAAGAAAGAATGAAATGGCTCAGCCTCAATGACTGAGCAAGAGAGT
TAGAGTCACCCACAGGAGAAAAGAAGAAAATAAACAGCACTGGGGTGAATTTGGGTCAGAGAAAACCTTA
AAATGCCAGAGGACAATGTGATGAAAGAGACCATTTGAAAGAAAGGGTTAACCTCATTCCATCAGTCATG
CCAGAGTTAGAGAATGGGCAGTCTGGAGTTACAAGATCACGATTAGCCTTCCCAGTATGTATACAGCATA
TTCCTGATAATGAGATGAAGCAAAGTTTGACAAGGTAAGATTGTATCCTATAGTAATATATAGATCAAAG
GCATGTTGCAGTAAATCTCCAACAGAAATAAGCCCGGGCAATGAAAACACAACTCAATTAATATGAATAC
GTGCTGTGCACCTAGACTGGGCAGATCTACCACTCCACTACCATATGAGAGATCCCTTATAACTTGTGGT
TTCTCCAGGCCAGCTGCTTCTGCTCTACTTTCCTTCCTCCTCCTCCTATGTCATCCTCTCCCTCACTCTT
TCTCTCCCAAAACTTTCAGCTGCACCTTCCCCTCTTCATCCCCCAATCAGTGGCTCTAGCCTTTATTTAT
AAATTAAGGTAGGAAGAAGGTTTATAGGAAATTACCTGAGTGTTGACGTGTTGATAACCCCACACAAGAG
AACAAAATTAATATCAAATATGATTAGCTCCAGGGTTATATGCAACAAAGGCATGATAAAGTGGTCATGA
TTTCATATGAGATGTACTGGACTCATGTGAAAAAACGTTTAAATACATGGGCTTACTCAAAATATAGACT
CATACCCCCAAGATGGGAAGAGACTGGTAACATTTGTACTGGAGGCTGGTCTGCTGTGGCAGCCATTAAC
ACAGTGGAGGGAAGAGCCTCAAAGAGTGAAATAGAGGAAGGGGAACAAATACAGTAAACCACCAGTTACT
ACTTAAAGGGCAGTGTTCTGATGTCCTAGGGAGGGCACTCCAAAATACCAATGGCCTTATCCTTAAATTT
ATTGTTTAATGAGCCTACACTGATCTCAGTGGCCCACTACTAAGGAGAAATGACAGGCACTTGAACAGCT
GATATGAGAACAGCTGGAGGCACAGTATACAGAAGAGTTTACAAGCCTATGGAACTCCCCTGTATTTTTT
TATGATGAGGAAATCTGAAAAATGTAAAATGTTGAAAGATTTAAGAGCAGTTATTAGAGTAGATCAACCA
ATGAGTCTCTTGCAGCCTGGAATTCTTTTATCTTGTTTGTAACAACAATCAGGCTCCATAAATTATAAAC
TATAAAAATTTACTTTATAAATTATAAATATATATATATGTGTGTCTGTAGATAGATAGATAGATAAATA
GATAGATAGATAGATAGATAGATAGATAGATATATGGATTTGATGGTTGCAGCAAATTCTAATTGGTTCC
AACAACCCTACTCACATAATACATTCATACAGGTTTGATAGATGGAGCTAAGTTTTAAATAAATTATTTT
TCTCCCATGGCTTATATATACACCACCAAAATTCTCAAAAATTAAAATGTGATTGTGTTGTATTTTTCTT
TTACTGAATGACTATAAAAAGTTACAACATTCTCCATAAATTTACATGAAAAAATATTATGTAGTGCAGG
TAAAGAAAACAAATTGACCCAAGAATGGTGTATATTCATTACTAAGCAACTTTTTAGATTCACAAAGTGT
GGGTAAACAAGGTAATTTTTTCAATCAGTTTTTTTTAACTGGCAGGCAGCAATTCAGAGTTACAATGAGA
AGATTAATAATTTTATTGTGTATTTTAAAATAAATCTTACAAAAATATTAATAGAATCACAAATTTATAC
CTTTGTATAAAAACAATCAGTCATTTCTACTTTAAGAAACAGAACTCACATCTACTCATCAATCATTTTA
TTAAGTCATATTACAAAGCTGAGTGCTAACATGGGTATAAGAAAACCATAACCTTATTCACCAGCCCAGC
GTCAAAAAGAAAAAAACCAGTCATATCAGCTGCTGCTTCAAGAGTTCTTGTTCCTTGACATTAACAAAAT
CCCTAGCTTAACTATTAAATTTTTTTTCAAAACTTCTAATTGATCCCTTAGATAAATGTTTGTGCTAACC
ATCGGGACACATCCCATGAGTTCTGAAGCAGTGTGTTGTTCTTCATGCATGGCCCTTTTGTAGAGCTGTG
AGTGTAGGGGAAGAGGGGGGAGAGAGAGCCCGTGTCCAGCCAGAGATCCTGTGCTCTGGGCAGGCAGACA
CGGGAGGACAACGGAACACTTTTCACTCGGCCTTTGGTGGGCATCTGGCTGTGTGAAGTTACTGACCCCA
CATGGTGGGGGATGGACAAGGGGCAGCCCCTGGTACCAGGAGCCCCAGGGCTACACTCTCGGCCCCAGAT
ATACAAGAAGAGGGCAGAGGGAGAGAGGCTCCCACACAGGCGAGAGTCCTTAGTCTGGTCTGTGGCTGGA
GCAGGGGAATTCCTTCTGATTGGAGATTAGGCACAGCTGATTAGGGGAAAGCCTACCCCATCATCCAAGC
ACAATGGACTTTGAGGAACAGAGCCAGTCTAAGCTTTTATAGCTTTATGGTAGAAAGGCAGGGAGAAAGG
AGAGAATGTGGAGAGAGACAGAGAGAGACTGGCCATGGCCAAGAGGAGGGAAGGGGGAAGAGAGAGAAAC
AGGAAAAGCTAGAAAGTAAGATAAGAGAAAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGCAAAGTG
GGGCCAAGCAGCCCCTTTTCTAGTGAGCTTGTCATCTCACAGTTGCTAGGTAACTGGGGAGGAGTTTAGT
CTGAAGGTCAGAAGCTTGGGACCTTGTGTATGTGACTACTAACCACAGCTTCTCCTGTCGGGACTGTGGG
AGCAGTAACTTTGACAGGAGACAGGGATCCAGGAGACATGAGGGAACACCTTCTGTCCCACATAGGTGGA
ATCGGTTGTACCAGGGTTCAGAACTCAACTCCACTGGAGACCAGCCTATGTGTGCATAGCCCATTGCCCT
ACAGCCTTTGACATTCTACAGAGTTCTGAGACTGGTAGAGATACAAAATAGCTAGGATTACACAGAGAAA
CACTGGCTTGACAATAAAACTTCCAAAACAAATATAAATGAATAAATACACAAATTGGAGCAAGTGAACT
TGCACTAAATCCATCAAAACTTGCACAGGATGGCTGTCTCCATAATGTTCAGATCTACTTCTATTAATGT
CATTAAGAAGACAAAGATTATGCACAAAAAGAAACAAAACAAGAAACCCAAAAGGTAAAGGCTCCAATTG
TAAGTAATAGACCCACAGTCTCTGAGGCCTGACTGTGCAGGTCCTCACCTTTGGTAATCAGCACTGAATG
CAGACCACTCCTCATGGACTTTGGGCTCAGGTTTGTTTTCCTTGTCCTTATTTTAAAAGGTAATTCATAG
AAATGAGATCCTGCCAGTATTGTGTACATGAGAAATAGAAAAATTGGTTTTCTTTGCTCTATTTTGTTTT
GTTTGGTTAATGACAGTTTCCAAATCAGCATTCTTTGCTTTGAGGTGCCCAGTGTGAGGTGAAGCTGGTA
GGGTCAGGGCAGCCTGGAGGGTCCCTGAAACACTCCTGTGCAGCCTCTGTAGTCACTGTGAGTGACTACT
GAATGACCTGGGTCCTTCAGGCTCTAAAGAAGGGGCTGGAGAGGGTGGAAATAATTTTTAATGGTGGAGG
TAGCACCTATTATCCAGACACCATGAAGGGCTGATTCACCATCTACAGAGATGATGCCAGAAACACACTT
TACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTGTGTGTGTGTGTGTGTGTGTGTGTGTG
TGTGTGTGTGTGTGTGTGTGTGTGAGTGTGTATTCATATATATATATATAGTGTGTATGTATATTCATAT
ATATATGTATATTCATAAGGTTGAGTAAATGGACTTAAACTGATTCCATCACAACTTCCATGGGATGGAT
ATTTCCCAGTGTTAAGACCTGTCAACATCACTGTCATTCAGGAGACAATGATTATGCACAACAAAACAAG
AAACCCAAAAGCAGAGGACTCCAATTACAATAGACCCAGACCCACAGTCTCTGAAGATTGACTGTACAGT
TCAACCCAGCCCTGTACTTCTCTTCCCTAGAATTTACATTACTGAGTAACTGAGGAAAGCTCTACAATAT
CTGTTCTCTATAGTGGTCAACACCTCCAAACACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTT
CTTGCCATAATGTAGACTACTTCAGCCTATTTTGTACTCCAGTTAACGAAACTCAAGACTAGCTGCATGT
TAGTCCTTATTCTGAAATATTATGAACAGGTGACCTCCCATCATTCACCAATGCAATAATCATATTTAGG
AATATGAGGTTTTATGAGATATAAGCACAAGGGAGAGAAAGTAAGAAAACTACATAGATATATAGACTGA
CATAAATCAAGACTTGCATGAGCTAGTGCCCAAGTACCATGTCCCTAAGTGGCAAGGAGTATCTTTTGAG
CCTAGTGAGATGAGGTACAAATCGGACTCTTACATCTTTTTAGATAAACATGTGAGATCAATGGACTAAA
GGCGTGAGCTGGGCTTCCTTGCAATCCATTTTCCATACAAGATAACAATAGATCTGGCTCCACAGACACG
ATGAGAATAGTCTTAATTAGTTCTTTAAGTAGAATGACTGATCACTAAGAGCCCAATTCCATACTAAATA
CTCTTCTGGATTATGCACAGATAAAAATTGCACATAGGGCATGGGGCACTGATCTCCCTGCACTACATGA
ATGGGGGCTCATTTACTAAATGTTCCCATGTTTCTTCCTAGTGCTGCACAGAGCAAATCCTACAACTTCC
TGCTTGTCTACAATGTAAACTCCAGACAGTACCAGAAAATCATTCCTTATGTTCCTCTCCAGGTGCTTCA
ACAAGCACAGTGCAAATTTCTGTCACCCTG

Molecule Role : Vaximmutor
Additional Molecule Role : Vaximmutor
Related Vaccine(s): Bordetella pertussis aroA mutant vaccine

IV. Vaccine Information

1. Actacel

a. Product Name:

Diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type b conjugate vaccine

b. Tradename:

Actacel

c. Manufacturer:

Sanofi Pasteur Ltd

d. Vaccine Ontology ID:

VO_0010705

e. Type:

Subunit vaccine

f. Status:

Licensed

g. Location Licensed:

Canada

h. Host Species for Licensed Use:

Human

i. Adjuvant: aluminum phosphate vaccine adjuvant

VO ID: VO_0000128

j. Preservative:

2 phenoxy ethanol

k. Immunization Route

Intramuscular injection (i.m.)

l. Storage

Refrigerate at 2° to 8°C.

m . Approved Age for Licensed Use

2 months to 7 years

n. Description

Products: Proteins + Conjugate.

2. Adacel

a. Product Name:

Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed

b. Tradename:

Adacel

c. Manufacturer:

Sanofi Pasteur, Ltd (USA: License #1726)

d. Vaccine Ontology ID:

VO_0000005

e. CDC CVX code:

20, 115

f. Type:

Toxoid vaccine

g. Status:

Licensed

h. Location Licensed:

USA: License #1726; Canada

i. Host Species for Licensed Use:

Human

j. Antigen

Pertussis

k. Adjuvant: aluminum phosphate vaccine adjuvant

VO ID: VO_0000128

l. Preparation

Clostridium tetani is grown in modified Mueller-Miller casamino acid medium without beef heart infusion. Tetanus toxin is detoxified with formaldehyde and purified by ammonium sulfate fractionation and diafiltration. Diphtheria and tetanus toxoids are individually adsorbed onto aluminum phosphate (FDA: Adacel).

m. Immunization Route

Intramuscular injection (i.m.)

n. Storage

Adacel vaccine should be stored at 2° to 8°C (35° to 46°F). DO NOT FREEZE

o . Approved Age for Licensed Use

Adacel vaccine is indicated for active booster immunization for the prevention of tetanus, diphtheria and pertussis as a single dose in persons 11 through 64 years of age.

p. Contraindication

A severe allergic reaction (e.g., anaphylaxis) after a previous dose of Adacel vaccine or any other tetanus toxoid, diphtheria toxoid or pertussis containing vaccine or any other component of this vaccine is a contraindication to vaccination with Adacel vaccine (FDA: Adacel).

q. Description

It is a sterile liquid suspension of tetanus and diphtheria toxoids and acellular pertussis components adsorbed onto aluminum phosphate, for intramuscular administration.

3. Adacel-Polio

a. Product Name:

Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine

b. Tradename:

Adacel-Polio

c. Manufacturer:

Sanofi Pasteur SA

d. Type:

Toxoid vaccine + Subunit vaccine + Inactivated or "killed" vaccine

e. Status:

Licensed

f. Location Licensed:

Canada

g. Host Species for Licensed Use:

Human

h. Preservative:

2-phenoxyethanol

i. Allergen:

Neomycin, Polymyxin B, Streptomycin

j. Immunization Route

Intramuscular injection (i.m.)

k. Storage

Store at 2° to 8°C (35° to 46°F), do not freeze.

l . Approved Age for Licensed Use

4 years and older.

m. Description

ADACEL®-POLIO is a sterile, uniform, cloudy, white suspension of tetanus and diphtheria toxoids and acellular pertussis vaccine adsorbed separately on aluminum phosphate and combined with inactivated poliomyelitis vaccine (vero cell origin) types 1, 2 and 3, and suspended in water for injection. Acellular pertussis vaccine is composed of five purified pertussis antigens (PT, FHA, PRN and FIM). (Product Monograph: Adacel-Polio)

4. B. pertussis BrkA protein vaccine

a. Vaccine Ontology ID:

VO_0011377

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

B. pertussis brkA

e. Gene Engineering of brkA

Type: Recombinant protein preparation
Description: Fraction BS was applied to a Mono Q Sepharose (Amersham, Biosciences) (0.5 mg protein per ml resin) previously equilibrated with 25 mM Tris–HCl, pH 8.0. Proteins were eluted with a NaCl gradient (0–1 M) in 25 mM Tris–HCl, pH 8.0, in 0.5 ml fractions at a flow rate of 1 ml/min. Elution was monitored at A280 nm. The fractions showing the same peak profile were pooled and eluted again under the same chromatography conditions. Samples were submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (T = 12.5% in 0.75 M Tris, 0.2% SDS, pH 8.8) and electrophoresis was performed at 60 mA in 25 mM Tris, 0.192 M glycine, 0.1% SDS, pH 8.3. The gel was stained with silver nitrate and fractions showing a similar molecular mass profile were pooled, concentrated by centrifugation at 440 × g in Centrifugal Ultrafree-20 tubes, 10 kDa (Millipore), and their protein concentration was evaluated. Four pools were formed (P1, P2, P3, P4), and used for immunization of mice (Cainelli et al., 2007).
Detailed Gene Information: Click here.

f. Immunization Route

Subcutaneous injection

g. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: Female BALB/c mice, 4–6 weeks old (Animal House of the Instituto Butantan) (9–15 mice/group) were subcutaneously injected three times at weekly intervals (days 0, 7, 14) with BS pools (P1, P2, P3, P4) (1 μg/0.1 ml/mouse), and two times (days 0 and 14) with 73 kDa or 60 kDa proteins (1 μg/0.1 ml/mouse) alone or mixed with Diphtheria-Pertussis-Tetanus (DPT) vaccine formulated without aluminum hydroxide (NA-DPT), (2 μl/mouse), (Instituto Butantan). Current DPT vaccine containing aluminum hydroxide (DPTBut) was used as control (2 μl/mouse) (Lot no. 0008147/0 and 0309132, Instituto Butantan). Non-immunized mice (injected with physiologic saline) were used as control (Cainelli et al., 2007).
Challenge Protocol: Animals were challenged by intracerebral route (i.c.) with live B. pertussis (strain 18323, NIH, USA), 21 days after the first immunization. Each mouse was inoculated with 30,000 live bacteria. Deaths were recorded until day 15 (Cainelli et al., 2007).
Efficacy: High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. The 73 kDa N-terminal alpha-domain of BrkA autotransporter protein, one protein identified in the fraction, stimulated antibodies against pertussis and induced a 42% protection rate against the challenge (Cainelli et al., 2007).

5. B. pertussis Cpn60 protein vaccine

a. Vaccine Ontology ID:

VO_0011357

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

B. pertussis cpn60/60 kDa chaperonin

e. Gene Engineering of cpn60

Type: Recombinant protein preparation
Description: Fraction BS was applied to a Mono Q Sepharose (Amersham, Biosciences) (0.5 mg protein per ml resin) previously equilibrated with 25 mM Tris–HCl, pH 8.0. Proteins were eluted with a NaCl gradient (0–1 M) in 25 mM Tris–HCl, pH 8.0, in 0.5 ml fractions at a flow rate of 1 ml/min. Elution was monitored at A280 nm. The fractions showing the same peak profile were pooled and eluted again under the same chromatography conditions. Samples were submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (T = 12.5% in 0.75 M Tris, 0.2% SDS, pH 8.8) and electrophoresis was performed at 60 mA in 25 mM Tris, 0.192 M glycine, 0.1% SDS, pH 8.3. The gel was stained with silver nitrate and fractions showing a similar molecular mass profile were pooled, concentrated by centrifugation at 440 × g in Centrifugal Ultrafree-20 tubes, 10 kDa (Millipore), and their protein concentration was evaluated. Four pools were formed (P1, P2, P3, P4), and used for immunization of mice (Cainelli et al., 2007).
Detailed Gene Information: Click here.

f. Immunization Route

Subcutaneous injection

g. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: Female BALB/c mice, 4–6 weeks old (Animal House of the Instituto Butantan) (9–15 mice/group) were subcutaneously injected three times at weekly intervals (days 0, 7, 14) with BS pools (P1, P2, P3, P4) (1 μg/0.1 ml/mouse), and two times (days 0 and 14) with 73 kDa or 60 kDa proteins (1 μg/0.1 ml/mouse) alone or mixed with Diphtheria-Pertussis-Tetanus (DPT) vaccine formulated without aluminum hydroxide (NA-DPT), (2 μl/mouse), (Instituto Butantan). Current DPT vaccine containing aluminum hydroxide (DPTBut) was used as control (2 μl/mouse) (Lot no. 0008147/0 and 0309132, Instituto Butantan). Non-immunized mice (injected with physiologic saline) were used as control (Cainelli et al., 2007).
Challenge Protocol: Animals were challenged by intracerebral route (i.c.) with live B. pertussis (strain 18323, NIH, USA), 21 days after the first immunization. Each mouse was inoculated with 30,000 live bacteria. Deaths were recorded until day 15 (Cainelli et al., 2007).
Efficacy: High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. The Cpn60/60 kDa chaperonin, one protein identified in the fraction, stimulated antibodies against pertussis and induced a 42% protection rate against the challenge (Cainelli et al., 2007).

6. B. pertussis CyaA protein vaccine

a. Vaccine Ontology ID:

VO_0011359

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

B. pertussis secreted adenylate cyclase (cyaA)

e. Gene Engineering of CyaA

Type: Recombinant protein preparation
Description: The AC was purified from culture supernatants using a camodulin affinity chromatography. The preparation consisted of two polypeptides of 45 and 43 kDa that are structurally related as described by Ladant et al (Guiso et al., 1989).
Detailed Gene Information: Click here.

f. Adjuvant: aluminum hydroxide vaccine adjuvant

VO ID: VO_0000127

g. Immunization Route

Subcutaneous injection

h. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: For active immunizations, Balb/c mice were given, subcutaneously, 3,ug of purified AC adsorbed on aluminium hydroxide, three times, at one week intervals . The mice were bled 5 days after the last injection in order to assess the presence of circulating anti-AC antibodies . The lethal challenge was performed 9 days after the final injection (Guiso et al., 1989).
Challenge Protocol: Bacterial suspension (50 pl) was injected intranasally to groups of 10 3-week-old female Balb/c mice (CERJ, St Berthevin, France), weighing 16±1 g . The LD 50 for the challenge inocula was determined daily by recording the number of dead mice . Pulmonary edema was quantified by lung weight (Guiso et al., 1989).
Efficacy: Active immunization with purified B. pertussis secreted adenylate cyclase (cyaA) protect mice against a lethal respiratory challenge with B. pertussis or B. parapertussis (Guiso et al., 1989).

7. B. pertussis DNA vaccine encoding Prn

a. Vaccine Ontology ID:

VO_0011391

b. Type:

DNA vaccine

c. Status:

Research

d. Antigen

B. pertussis pertactin precursor prn2

e. Gene Engineering of Prn

Type: DNA vaccine construction
Description: To construct a prn mutant, amplification of the region containing the whole prn2 gene of the CCHMC1 strain was performed using PRN-F GGCACAGGACCGGCGCGTGTTTCGCGCACGACTCT) and PRN-R (CGCGTGGTGCGCCTGAAAGGCGGCGATGCCTTCA) with attB adaptors. The PCR products were cloned into pDONR221 to obtain pDONR-PTXA1 and pDONR-PRN2 by site-specific recombination techniques using the Gateway cloning system (Invitrogen). The regions transferred into the pDONR221 plasmid were sequenced for verification. pDONR-PTXA1 or pDONR-PRN2 was mixed with pABB-CRS2 to obtain pABB-PTXA1 and pABB-PRN2 by using the Gateway cloning system. pABB-PTXA1 or pABB-PRN2 was introduced into E. coli SM10pir and mobilized into the B. pertussis strain Tohama by conjugation (Komatsu et al., 2010).
Detailed Gene Information: Click here.

f. Vector:

DONR221 (Invitrogen, Carlsbad, CA) and pABB-CRS2 (Komatsu et al., 2010).

g. Immunization Route

Subcutaneous injection

h. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: 3.5-week-old female BALB/c mice (Japan SLC, Hamamatsu) were immunized by two subcutaneous injections of 0.25 SHDs (0.125 ml) over a 2-week interval (Komatsu et al., 2010).
Challenge Protocol: Two weeks after the second immunization, 50 µl of a suspension containing approximately 6 x 10⁶ CFU of B. pertussis was instilled intranasally into mice anesthetized by intraperitoneal injection with pentobarbital sodium (Nembutal; Abbott Laboratories, Abbott Park, IL). Two hours (day 0) or 2, 5, or 8 days after the challenge, the mice were euthanized by pentobarbital injection (Komatsu et al., 2010).
Efficacy: While the vaccine was effective against all of the B. pertussis strains regardless of the allele expression pattern, the strain expressing ptxA1 and prn2 displayed a survival advantage over the other strains (Komatsu et al., 2010).

8. B. pertussis DNA vaccine pcDNA/S1

a. Vaccine Ontology ID:

VO_0004545

b. Type:

DNA vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Gene Engineering of S1

Type: DNA vaccine construction
Description:
Detailed Gene Information: Click here.

f. Vector:

pcDNA.3.1(+) (Kamachi et al., 2003)

g. Immunization Route

Gene gun

h. Mouse Response

Vaccination Protocol: For immunization, 0.5 mg of gold particles were coated with 2 μg of plasmid DNA and 0.5 mg gold per injection was used. Mice were immunized intradermally three times on days 0, 14, and 28 using a Helios Gene Gun at a helium gas pressure of 400 psi (Kamachi et al., 2003).
Immune Response: Gene gun vaccination was employed for the delivery of pcDNA/S1, and the induction of IgG1 predominant antibody production was observed (Kamachi et al., 2003).
Challenge Protocol: Immunized BALB/c mice were challenged intranasally with B. pertussis strain 18–323 (Kamachi et al., 2003).
Efficacy: In the pcDNA/S1-immune group, five out of 10 mice survived 24 hours after the challenge, whereas all of the mice in the pcDNA-immune group died within 24 hours (Kamachi et al., 2003).

9. B. pertussis FhaB and 69 kDa OMP protein vaccine

a. Vaccine Ontology ID:

VO_0011498

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

Combination of the B. pertussis 69-kDa outer membrane protein and filamentous hemagglutinin (fhaB)

e. Gene Engineering of fhaB

Type: Recombinant protein preparation
Description: A crystal clear supernatant of 5-day-old static cultures containing proteolysis inhibitor was purified. To remove impurities, the FHA was precipitated by overnight dialysis against 25-30 volumes of buffer A at 4 C, and the precipitate was collected by centrifugation. The precipitated FHA was dissolved in the smallest possible volume of 40 mM B-alanine buffer at pH 3.5, clarified by centrifugation, and applied at room temperature at a flow of 30 ml/h to a Superose 12 column. The retained highly purified FHA was eluted (Novotny et al., 1991).
Detailed Gene Information: Click here.

f. Adjuvant: Alhydrogel vaccine adjuvant

VO ID: VO_0001241
Description: 4.0 ml Alhydrogel (Novotny et al., 1991).

g. Immunization Route

Intramuscular injection (i.m.)

h. Mouse Response

Vaccination Protocol: Groups of mice were injected intraperitoneally with 0.5 ml volumes of four concentrations (Novotny et al., 1991).
Challenge Protocol: Mice were challenged intracerebrally 14 days after antigen injection. The challenge dose contained 300-400 LD50, and a 1:1250 dilution of the challenge does contained ~ 10cfu. All mice were challenged within 90 minutes after the challenge suspension was thawed; the challenge was injected using a 1 ml syringe in a Hamilton PB600-I dispensor that reproducibly delivers 20-ul voumes (Novotny et al., 1991).
Efficacy: A combination of the 69-kDa outer membrane protein and filamentous hemagglutinin (fhaB), both isolated from lymphocytosis promoting factor (LPF; pertussis toxin) minus mutants of Bordetella pertussis, is protective in the mouse intracerebral challenge potency (Kendrick) test (Novotny et al., 1991).

10. B. pertussis PTx protein vaccine

a. Vaccine Ontology ID:

VO_0011361

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

B. pertussis pertussis toxin (PTx)

e. Gene Engineering of ptxE

Type: Recombinant protein preparation
Description: Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002).
Detailed Gene Information: Click here.

f. Gene Engineering of PtxA

Type: Recombinant protein preparation
Description: Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002).
Detailed Gene Information: Click here.

g. Gene Engineering of ptxB

Type: Recombinant protein preparation
Description: Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002).
Detailed Gene Information: Click here.

h. Gene Engineering of ptxC

Type: Recombinant protein preparation
Description: Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002).
Detailed Gene Information: Click here.

i. Gene Engineering of ptxD

Type: Recombinant protein preparation
Description: Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002).
Detailed Gene Information: Click here.

j. Adjuvant: aluminum hydroxide vaccine adjuvant

VO ID: VO_0000127

k. Immunization Route

Intraperitoneal injection (i.p.)

l. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: Mice were removed from their cages, weighed, and placed on a stainless steel rack that fits inside of the Plexiglas aerosol chamber (40 by 40 by 40 cm). The 21-h culture of B. pertussis was suspended in sterile PBS to a concentration of approximately 2 × 10⁹ CFU/ml of inoculum. This inoculum was delivered to the mice using a standard nebulizer (model 647; Devilbis, Somerset, Pa.) with a set pressure of 1.5 kg/cm2. The chamber and the nebulizer were enclosed in a biosafety level-2 hood and certified prior to use to document that airflow barriers were maintained. Uniformity of aerosol in the chamber was maintained with the use of two PABST 900 series AC fans (Newark Supply, Newark, N.J.). The even dispersion of the aerosol was confirmed with a light laser (Bruss and Siber, 2002).
Challenge Protocol: Mice were exposed to nebulization for 30 min and removed 30 min after termination of aerosol. The completion of the aerosol represented time 0. Mice were removed from the box and replaced into their cages. Cages were checked daily for mortality (Bruss and Siber, 2002).
Efficacy: BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002).

11. Boostrix

a. Product Name:

Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed

b. Tradename:

Boostrix

c. Manufacturer:

GlaxoSmithKline Biologicals

d. Vaccine Ontology ID:

VO_0000015

e. CDC CVX code:

20, 115

f. Type:

Toxoid vaccine

g. Status:

Licensed

h. Location Licensed:

USA (License #1617)

i. Host Species for Licensed Use:

Human

j. Adjuvant: aluminum phosphate vaccine adjuvant

VO ID: VO_0000128

k. Preparation

Tetanus toxin is produced by growing Clostridium tetani in a modified Latham medium derived from bovine casein. Toxins are detoxified with formaldehyde, concentrated by ultrafiltration, and purified by precipitation, dialysis, and sterile filtration (FDA: Boostrix).

l. Immunization Route

Intramuscular injection (i.m.)

m. Storage

Store refrigerated between 2º and 8ºC (36º and 46ºF). Do not freeze.

n . Approved Age for Licensed Use

BOOSTRIX is approved for use in individuals 10 through 64 years of age

o. Contraindication

A severe allergic reaction after a previous dose of any tetanus toxoid-diphtheria toxoid or pertussis antigen containing vaccine or any component of this vaccine is a contraindication to administration of BOOSTRIX (FDA: Boostrix).

p. Description

BOOSTRIX (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed) is a noninfectious, sterile, vaccine for intramuscular administration. It contains tetanus toxoid, diphtheria toxoid, and pertussis antigens (inactivated pertussis toxin [PT] and formaldehyde-treated filamentous hemagglutinin [FHA] and pertactin). The antigens are the same as those in INFANRIX, but BOOSTRIX is formulated with reduced quantities of these antigens (FDA: Boostrix).

12. Boostrix-Polio

a. Product Name:

Combined diphtheria, tetanus, acellular pertussis (adsorbed) and inactivated poliomyelitis vaccine

b. Tradename:

Boostrix-Polio

c. Manufacturer:

GlaxoSmithKline

d. Type:

Toxoid vaccine + Subunit vaccine + Inactivated or "killed" vaccine

e. Status:

Licensed

f. Location Licensed:

Canada

g. Host Species for Licensed Use:

Human

h. Allergen:

Neomycin, Polymyxin B

i. Immunization Route

Intramuscular injection (i.m.)

j. Storage

Store at 2° to 8°C (35° to 46°F), do not freeze.

k . Approved Age for Licensed Use

4 years of age and older.

l. Description

BOOSTRIX®-POLIO (combined diphtheria, tetanus, acellular pertussis and inactivated poliomyetitis) vaccine contains diphtheria toxoid, tetanus toxoid, three purified pertussis antigens [pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (69 kDalton outer membrane protein)] adsorbed onto aluminum salts and inactivated polio virus types 1, 2 and 3. (GSK: Boostrix-Polio)

13. Bordetella pertussis aroA mutant vaccine

a. Vaccine Ontology ID:

VO_0002807

b. Type:

Live, attenuated vaccine

c. Status:

Research

d. Gene Engineering of aroA

Type: Gene mutation
Description:
Detailed Gene Information: Click here.

e. Preparation

A DNA fragment encoding a kanamycin resistance determinant was used to insertionally inactivate the cloned aroA gene of Bordetella pertussis in Escherichia coli K-12, and a conjugative shuttle vector system based on the suicide vector pRTP1 was used to deliver the mutations from E. coli back into B. pertussis CN2992FS and BP1. The aroA mutation was introduced by allelic exchange into the chromosome of B. pertussis, resulting in otherwise isogenic parental and aroA mutant pairs. The B. pertussis aroA mutants grew well on laboratory medium supplemented with aromatic compounds but failed to grow on unsupplemented medium (Roberts et al., 1990).

f. Immunization Route

intracerebral challenge

g. Mouse Response

Persistence: The B. pertussis aroA mutants expressed the normal B. pertussis extracellular, virulence-associated proteins (Roberts et al., 1990).
Efficacy: Mice exposed to three separate aerosols of live B. pertussis aroA bacteria were protected against lung colonization after being exposed to an aerosol containing the virulent parental B. pertussis strain. High-level antibodies against B. pertussis rapidly appeared in the sera of mice immunized by aerosol with the B. pertussis aroA strains and challenged with the virulent parent (Roberts et al., 1990).

14. Bordetella pertussis BPZE vectored vaccine

a. Vaccine Ontology ID:

VO_0004608

b. Type:

Recombinant vector vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Antigen

The pertussis toxin gene, which encodes a highly virulent toxin (Mielcarek et al., 2006).

f. Vector:

Bordetella pertussis BPZE, which is attenuated for 3 different toxins: the pertussis toxin, the dermonecrotic toxin, and the tracheal cytotoxins (Mielcarek et al., 2006).

g. Immunization Route

intranasal immunization

h. Virulence

The pertussis toxin itself if extremely virulent, but after thorough and careful attenuation, the virulence is basically gone (Mielcarek et al., 2006).

i. Description

This is an intranasal vaccine because pathogenic B. pertussis colonizes the respiratory tract of humans. The vaccine itself has been shown to only need one inoculation in order to elicit protection, making it a good candidate to be a vaccine vector for other diseases (Mielcarek et al., 2006).

j. Mouse Response

Vaccination Protocol: The mice were vaccinated with highly-attenuated B. pertussis in order to prepare for challenge with virulent wild-type B. pertussis (Mielcarek et al., 2006).
Vaccine Immune Response Type: VO_0000287
Challenge Protocol: After the mice had been inoculated with attenuated B. pertussis (which after a month had colonized the entire mouse respiratory tract) they were challenged with virulent wild-type B. pertussis (Mielcarek et al., 2006).
Efficacy: A single intranasal inoculation of mice with the B. pertussis vaccine vector induced the same level of protection, if not higher, as two injections of the commercial acellular vaccine (Mielcarek et al., 2006) .
Description: Inoculation with the B. pertussis vaccine vector shows protective immunity which rivals that of the vaccines currently on the market.

15. Bordetella pertussis dnt mutant vaccine

a. Vaccine Ontology ID:

VO_0002808

b. Type:

Live, attenuated vaccine

c. Status:

Research

d. Gene Engineering of dnt

Type: Gene mutation
Description:
Detailed Gene Information: Click here.

e. Preparation

his strain was obtained by genetically inactivating pertussis toxin via two point mutations in the ptx gene, by deleting dnt encoding dermonecrotic toxin, and by replacing the B. pertussis ampG gene by Escherichia coli ampG, resulting in the removal of tracheal cytotoxin (Feunou et al., 2008).

f. Immunization Route

intranasal immunization

g. Mouse Response

Persistence: The dnt mutant in B. pertussis yielded a highly attenuated strain that was still able to transiently colonize the mouse respiratory tract [Ref1805:Feunou et al., 2008.
Efficacy: A single intranasal administration of BPZE1(dnt mutant vaccine) induced full protection in adult mice (8 weeks old), as well as in infant mice (3 weeks old), whereas commercial acellular pertussis vaccine (aPV) only partially protected infant mice, even after repetitive doses (Feunou et al., 2008).

16. DAPTACEL

a. Product Name:

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed

b. Tradename:

DAPTACEL

c. Manufacturer:

Sanofi Pasteur, Ltd.

d. Vaccine Ontology ID:

VO_0000029

e. CDC CVX code:

20, 106

f. Type:

Toxoid vaccine

g. Status:

Licensed

h. Location Licensed:

USA (License #1726)

i. Host Species for Licensed Use:

Human

j. Antigen

Isotonic suspension of pertussis antigens and diphtheria and tetanus toxoids (FDA: DAPTACEL).

k. Adjuvant: aluminum phosphate vaccine adjuvant

VO ID: VO_0000128
Description: DAPTACEL is a vaccine indicated for active immunization against diphtheria, tetanus and pertussis as a five-dose series in infants and children 6 weeks through 6 years of age.

l. Preparation

m. Immunization Route

Intramuscular injection (i.m.)

n. Storage

Should be stored at 2° to 8°C (35° to 46°F). DO NOT FREEZE.

o . Approved Age for Licensed Use

DAPTACEL is a vaccine indicated for active immunization against diphtheria, tetanus and pertussis as a five dose series in infants and children 6 weeks through 6 years of age (prior to 7th birthday) (FDA: DAPTACEL).

p. Contraindication

Severe allergic reaction (e.g. anaphylaxis) after a previous dose of any diphtheria toxoid, tetanus toxoid, or pertussis-containing vaccine, or any component of DAPTACEL, encephalopathy within 7 days of a previous pertussis-containing vaccine with no other identifiable cause and, progressive neurologic disorder until a treatment regimen has been established and the condition has stabilized (FDA: DAPTACEL).

q. Description

DAPTACEL is a vaccine indicated for active immunization against diphtheria, tetanus and pertussis as a five-dose series in infants and children 6 weeks through 6 years of age.

17. Infanrix

a. Product Name:

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed

b. Tradename:

Infanrix

c. Manufacturer:

GlaxoSmithKline Biologicals

d. Vaccine Ontology ID:

VO_0000064

e. CDC CVX code:

f. Type:

Toxoid vaccine

g. Status:

Licensed

h. Location Licensed:

USA (License #1617 )

i. Host Species for Licensed Use:

Human

j. Antigen

Diphtheria and tetanus toxoids and 3 pertussis antigens [inactivated pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (69 kiloDalton outer membrane protein)] (FDA: Infanrix).

k. Adjuvant: aluminum hydroxide vaccine adjuvant

VO ID: VO_0000127

l. Preparation

Tetanus toxin is produced by growing Clostridium tetani in a modified Latham medium derived from bovine casein. The toxin is detoxified with formaldehyde, concentrated by ultrafiltration, and purified by precipitation, dialysis, and sterile filtration (FDA: Infanrix).

m. Immunization Route

Intramuscular injection (i.m.)

n. Storage

Store INFANRIX refrigerated between 2° and 8°C (36° and 46°F). Do not freeze.

o . Approved Age for Licensed Use

INFANRIX is indicated for active immunization against diphtheria, tetanus, and pertussis (whooping cough) as a 5-dose series in infants and children 6 weeks to 7 years of age (prior to seventh birthday). INFANRIX should not be administered to any infant before the age of 6 weeks, or to individuals 7 years of age or older (FDA: Infanrix).

p. Contraindication

Hypersensitivity to any component of the vaccine is a contraindication, the vaccine should not be administered to anyone with encephalopathy, progressive neurological disorders, or an allergic reaction to a previous dose (FDA: Infanrix).

q. Description

The vaccine is an noninfectious, sterile combination of diphtheria and tetanus toxoids and 3 pertussis antigens [inactivated pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (69 kiloDalton outer membrane protein)] adsorbed onto aluminum hydroxide (FDA: Infanrix).

18. Infanrix -IPV/Hib

a. Product Name:

Diphtheria, tetanus, pertussis (acellular component), poliomyelitis (inactivated) and Haemophilus type b conjugate vaccine (adsorbed)

b. Tradename:

Infanrix -IPV/Hib

c. Manufacturer:

GlaxoSmithKline

d. Vaccine Ontology ID:

VO_0010722

e. CDC CVX code:

120

f. Type:

Subunit vaccine + Inactivated or "killed" vaccine

g. Status:

Licensed

h. Location Licensed:

Canada

i. Host Species for Licensed Use:

Human

j. Adjuvant: aluminum hydroxide vaccine adjuvant

VO ID: VO_0000127

k. Preservative:

2 phenoxy ethanol

l. Allergen:

Polymyxin B Neomycin , Latex in plunger stopper of prefilled syringe

m. Immunization Route

Intramuscular injection (i.m.)

n. Storage

Store in a refrigerator (2°C – 8°C).

o . Approved Age for Licensed Use

2 months to 6 years of age.

p. Description

Products: Proteins + killed virus + conjugate. Other components: Formaldehyde Polysorbate 80, Lactose.

19. Infanrix-hexa

a. Product Name:

Combined diphtheria and tetanus toxoids, acellular pertussis, hepatitis B (recombinant), inactivated poliomyelitis and adsorbed conjugated Haemophilus influenzae type b vaccine

b. Tradename:

Infanrix-hexa

c. Manufacturer:

GlaxoSmithKline

d. Vaccine Ontology ID:

VO_0010719

e. Type:

Subunit vaccine + Inactivated or "killed" vaccine

f. Status:

Licensed

g. Location Licensed:

Canada

h. Host Species for Licensed Use:

Human

i. Adjuvant: aluminum phosphate vaccine adjuvant

VO ID: VO_0000128

j. Adjuvant: aluminum hydroxide vaccine adjuvant

VO ID: VO_0000127

k. Preservative:

2 phenoxy ethanol

l. Allergen:

Polymyxin B Neomycin, Latex in plunger stopper of prefilled syringe

m. Immunization Route

Intramuscular injection (i.m.)

n. Storage

Should be stored at 2° to 8°C (35° to 46°F).

o . Approved Age for Licensed Use

Under 7 years of age.

p. Description

Products: Proteins + killed viruses + conjugate. Other components: Yeast protein Formaldehyde, Lactose, Polysorbate 20 and 80.

20. Infanrix-IPV

a. Product Name:

Diphtheria, tetanus, pertussis (acellular, component) and poliomyelitis (inactivated) vaccine (adsorbed)

b. Tradename:

Infanrix-IPV

c. Manufacturer:

GlaxoSmithKline

d. Vaccine Ontology ID:

VO_0010721

e. Type:

Subunit vaccine + Inactivated or "killed" vaccine

f. Status:

Licensed

g. Location Licensed:

Canada

h. Host Species for Licensed Use:

Human

i. Adjuvant: aluminum hydroxide vaccine adjuvant

VO ID: VO_0000127

j. Preservative:

2 phenoxy ethanol

k. Allergen:

Polymyxin B Neomycin , Latex in plunger stopper of prefilled syringes

l. Immunization Route

Intramuscular injection (i.m.)

m. Storage

Store in a refrigerator (2°C - 8°C).

n . Approved Age for Licensed Use

2 months to 6 years of age.

o. Description

Products: Proteins + killed virus. Other components: Formaldehyde, Polysorbate 80.

21. Infanrix/Hib

a. Product Name:

Combined diphtheria, tetanus, acellular pertussis (DTPa) and Haemophilus influenza type b vaccine

b. Tradename:

Infanrix/Hib

c. Manufacturer:

GlaxoSmithKline

d. Vaccine Ontology ID:

VO_0010720

e. Type:

Subunit vaccine

f. Status:

Licensed

g. Location Licensed:

Canada

h. Host Species for Licensed Use:

Human

i. Adjuvant: aluminum hydroxide vaccine adjuvant

VO ID: VO_0000127

j. Preservative:

2 phenoxy ethanol

k. Allergen:

Latex in plunger stopper of prefilled syringe

l. Immunization Route

Intramuscular injection (i.m.)

m. Storage

Refrigerated stored between +2°C and +8°C.

n . Approved Age for Licensed Use

15 months and older

o. Description

Products: Proteins + conjugate. Other components: Formaldehyde, Lactose.

22. KINRIX

a. Product Name:

Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine

b. Tradename:

KINRIX

c. Manufacturer:

GlaxoSmithKline

d. Vaccine Ontology ID:

VO_0000067

e. Type:

Toxoid vaccine + Subunit vaccine + Inactivated or "killed" vaccine

f. Status:

Licensed

g. Location Licensed:

USA

h. Host Species for Licensed Use:

Human

i. Allergen:

Latex, Neomycin, Polymyxin B.

j. Preparation

The diphtheria toxin is produced by growing Corynebacterium diphtheriae in Fenton medium containing a bovine extract. After, they are detoxified with formaldehyde, concentrated by ultrafiltration, and purified by precipitation, dialysis, and sterile filtration.

k. Immunization Route

Intramuscular injection (i.m.)

l. Storage

Store refrigerated between 2° and 8°C (36° and 46°F), do not freeze.

m . Approved Age for Licensed Use

4 to 6 years of age.

n. Contraindication

A severe allergic reaction (e.g., anaphylaxis) after a previous dose of any diphtheria toxoid, tetanus toxoid, pertussis or poliovirus-containing vaccine, or to any component of KINRIX, including neomycin and polymyxin B, encephalopathy within 7 days of administration of a previous pertussis-containing vaccine and progressive neurologic disorders.

o. Description

A single dose of KINRIX is indicated for active immunization against diphtheria, tetanus, pertussis, and poliomyelitis as the fifth dose in the diphtheria, tetanus, and acellular pertussis (DTaP) vaccine series and the fourth dose in the inactivated poliovirus vaccine (IPV) series in children 4 through 6 years of age whose previous DTaP vaccine doses have been with INFANRIX and/or PEDIARIX for the first three doses and INFANRIX for the fourth dose. (FDA: KINRIX)

23. Pediacel

a. Product Name:

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine and Haemophilus b Conjugate Vaccine (Tetanus Protein – Conjugate)

b. Tradename:

Pediacel

c. Manufacturer:

Sanofi Pasteur Ltd

d. Vaccine Ontology ID:

VO_0010730

e. Type:

Subunit vaccine + Inactivated or "killed" vaccine

f. Status:

Licensed

g. Location Licensed:

Canada

h. Host Species for Licensed Use:

Human

i. Adjuvant: aluminum phosphate vaccine adjuvant

VO ID: VO_0000128

j. Preservative:

2 phenoxy ethanol

k. Allergen:

Neomycin Polymyxin B Streptomycin, Latex in stopper of vial

l. Immunization Route

Intramuscular injection (i.m.)

m. Storage

Store at 2° to 8°C (35° to 46°F).

n . Approved Age for Licensed Use

2 months to 6 years of age.

o. Description

Products: Proteins, killed virus + conjugate. Other components: Bovine serum Formaldehyde, Polysorbate 80.

24. Pediarix

a. Product Name:

Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined

b. Tradename:

Pediarix

c. Manufacturer:

GlaxoSmithKline Biologicals

d. Vaccine Ontology ID:

VO_0000082

e. CDC CVX code:

110

f. Type:

Toxoid vaccine

g. Status:

Licensed

h. Location Licensed:

United States

i. Host Species for Licensed Use:

Human

j. Adjuvant: aluminum hydroxide vaccine adjuvant

VO ID: VO_0000127

k. Allergen:

yeast, neomycin,polymyxin B

l. Preparation

The diphtheria toxin is produced by growing Corynebacterium diphtheriae in Fenton medium containing a bovine extract. The diphtheria, tetanus, and pertussis antigens are individually adsorbed onto aluminum hydroxide then diluted and combined to produce the final formulated vaccine (FDA: Pediarix).

m. Immunization Route

Intramuscular injection (i.m.)

n. Storage

The vaccine should be refrigerated between 2º and 8ºC (36º and 46ºF). Do not freeze.

o . Approved Age for Licensed Use

PEDIARIX is indicated for active immunization against diphtheria, tetanus, pertussis (whooping cough), all known subtypes of hepatitis B virus, and poliomyelitis caused by poliovirus Types 1, 2, and 3 as a three-dose primary series in infants born of HBsAg-negative mothers, beginning as early as 6 weeks of age. PEDIARIX should not be administered to any infant before the age of 6 weeks, or to individuals 7 years of age or older.

p. Contraindication

Hypersensitivity to any component of the vaccine, including yeast, neomycin, and polymyxin B, is a contraindication. The vaccine should also not be administered to anyone with a previous allergic reaction to a dose of the vaccine (FDA: Pediarix).

q. Description

It contains diphtheria and tetanus toxoids, 3 pertussis antigens (inactivated pertussis toxin [PT] and formaldehyde-treated filamentous hemagglutinin [FHA] and pertactin [69 kiloDalton outer membrane protein]), hepatitis B surface antigen, plus poliovirus Type 1 (Mahoney), Type 2 (MEF-1), and Type 3 (Saukett) (FDA: Pediarix).

25. Pentacel

a. Product Name:

Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine

b. Tradename:

Pentacel

c. Manufacturer:

Sanofi Pasteur Limited

d. Vaccine Ontology ID:

VO_0000084

e. CDC CVX code:

120

f. Type:

Subunit vaccine + Inactivated or "killed" vaccine

g. Status:

Licensed

h. Location Licensed:

USA (License #1726), Canada

i. Host Species for Licensed Use:

Human

j. Adjuvant: aluminum phosphate vaccine adjuvant

VO ID: VO_0000128

k. Preservative:

2 phenoxy ethanol

l. Allergen:

Polymyxin B, Neomycin

m. Preparation

Corynebacterium diphtheriae is grown in modified Mueller’s growth medium. After purification by ammonium sulfate fractionation, the diphtheria toxin is detoxified with formaldehyde and diafiltered (FDA: Pentacel).

n. Immunization Route

Intramuscular injection (i.m.)

o. Storage

Store at 2° to 8°C (35° to 46°F). Do not freeze.

p . Approved Age for Licensed Use

6 weeks to 4 years of age.

q. Contraindication

A severe allergic reaction (e.g., anaphylaxis) after a previous dose of Pentacel vaccine, any ingredient of this vaccine, or any other tetanus toxoid, diphtheria toxoid, pertussis-containing vaccine, inactivated poliovirus vaccine or H influenzae type b vaccine is a contraindication (FDA: Pentacel).

r. Description

It consists of a Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus (DTaP-IPV) component and an ActHIB® vaccine component. Pentacel vaccine is indicated for active immunization against diphtheria, tetanus, pertussis, poliomyelitis and invasive disease due to Haemophilus influenzae type b (FDA: Pentacel).

26. Quadracel

a. Product Name:

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine

b. Tradename:

Quadracel

c. Manufacturer:

Sanofi Pasteur Ltd

d. Vaccine Ontology ID:

VO_0010736

e. Type:

Subunit vaccine + Inactivated or "killed" vaccine

f. Status:

Licensed

g. Location Licensed:

Canada

h. Host Species for Licensed Use:

Human

i. Adjuvant: aluminum phosphate vaccine adjuvant

VO ID: VO_0000128

j. Preservative:

2 phenoxy ethanol

k. Allergen:

Polymyxin B, Neomycin

l. Immunization Route

Intramuscular injection (i.m.)

m. Storage

Store at 2 to 8C (35 to 46F). Do not freeze.

n . Approved Age for Licensed Use

2 months to six years of age.

27. rBCG-S1PT

a. Vaccine Ontology ID:

VO_0004790

b. Type:

Recombinant vector vaccine

c. Status:

Licensed

d. Host Species for Licensed Use:

Mouse

e. Antigen

BCG vaccine with S1 subunit of detoxified B. pertussis toxin; PT-9K/129G (Nascimento et al., 2008).

f. Immunization Route

Intramuscular injection (i.m.)

g. Mouse Response

Vaccination Protocol: Mice were immunized with 50μl of one-tenth dose of an adult mouse of DTP at day 5 (or day 12 as specified) or 10⁵ CFU of BCG or rBCG-S1PT on day 5 according to different regimens (Nascimento et al., 2008).
Vaccine Immune Response Type: VO_0003057
Challenge Protocol: Mice were subjected to intracerebral inoculation with a lethal dose of B. pertussis with approximately 3 x 10⁴, 3 x 10⁵, or 9 x 10⁵ CFU (in 30μl) on day 21 after birth.
Efficacy: A single dose of rBCG-S1PT at day 5 led to a 100% survival of mice, and even at an extremely high challenge dose (300 times the lethal adult dose) rBCG-S1PT still induced 50% survival of neonate-immunized mice. Mice immunized with BCG alone experienced a protective effect of 80%, however at a higher challenge dose, this effect was reduced to 50%. Mice immunized with DTP showed no protection (Nascimento et al., 2008).

28. S. gordonii-PT

a. Vaccine Ontology ID:

VO_0004670

b. Type:

Recombinant vector vaccine

c. Status:

Research

d. Host Species for Licensed Use:

Baboon

e. Preparation

(Lee et al., 1999)

f. Immunization Route

Intramuscular injection (i.m.)

29. Tripacel

a. Product Name:

Pertussis Vaccine-Acellular, Combined with Diphtheria and Tetanus Toxoids (Adsorbed)

b. Tradename:

Tripacel

c. Manufacturer:

Sanofi Pasteur Ltd

d. Vaccine Ontology ID:

VO_0010742

e. Type:

Subunit vaccine

f. Status:

Licensed

g. Location Licensed:

Canada

h. Host Species for Licensed Use:

Human

i. Adjuvant: aluminum phosphate vaccine adjuvant

VO ID: VO_0000128

j. Preservative:

2-phenoxyethanol

k. Allergen:

Latex in stopper

l. Immunization Route

Intramuscular injection (i.m.)

m. Storage

Store at at 2° to 8°C.

n . Approved Age for Licensed Use

2 months up to 8 years of age.

30. Tripedia

a. Product Name:

Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed

b. Tradename:

Tripedia

c. Manufacturer:

Sanofi Pasteur, Inc.

d. Vaccine Ontology ID:

VO_0000112

e. CDC CVX code:

f. Type:

Toxoid vaccine

g. Status:

Licensed

h. Location Licensed:

USA (FDA License #1725)

i. Host Species for Licensed Use:

Human

j. Adjuvant: Bordetella pertussis component vaccine adjuvant

VO ID: VO_0000193
Description: Tripedia vaccine combines diptheria and tetanus toxoids with purified pertussis antigens. It consists of 3 doses administered at intervals of 4-8 weeks (FDA: Tripedia).

k. Immunization Route

Intramuscular injection (i.m.)

l. Storage

Store between 2 and 8 degrees Celsius. DO NOT FREEZE.

m . Approved Age for Licensed Use

Tripedia vaccine is indicated for active immunization against diphtheria, tetanus, and pertussis simultaneously in infants and children 6 weeks to 7 years of age (prior to seventh birthday). Due to substantial risks of complications of the disease, completion of a primary series of pertussis vaccine early in life is strongly recommended (FDA: Tripedia).

n. Contraindication

This vaccine should not be administered to anyone with a known hypersensitivity to any component of the vaccine.

o. Description

Tripedia vaccine combines diptheria and tetanus toxoids with purified pertussis antigens. It consists of 3 doses administered at intervals of 4-8 weeks (FDA: Tripedia).

31. VC-TetC/Tcf

a. Product Name:

VC expressing B. pertussis TetC/Tcf

b. Vaccine Ontology ID:

VO_0004781

c. Type:

Recombinant vector vaccine

d. Status:

Research

e. Host Species for Licensed Use:

Baboon

f. Gene Engineering of TcfA

Type: Recombinant protein preparation
Description: An attenuated strain of Vibrio cholerae was used as a carrier for the expression of heterologous antigens such as fragment C from tetanus toxin (TetC) and tracheal colonization factor from Bordetella pertussis (Tcf) (Chen et al., 1998).
Detailed Gene Information: Click here.

g. Preparation

An attenuated strain of Vibrio cholerae was used as a carrier for the expression of heterologous antigens such as fragment C from tetanus toxin (TetC) and tracheal colonization factor from Bordetella pertussis (Tcf) (Chen et al., 1998).

h. Immunization Route

intranasal immunization

i. Mouse Response

Vaccine Immune Response Type: VO_0000287
Challenge Protocol: Mice were challenged with wild-type B. pertussis (Chen et al., 1998).
Efficacy: Mice vaccinated with IEM101 expressing Tcf experienced significant reduction in bacterial colonization of their tracheas (Chen et al., 1998).

V. References

1. Bruss and Siber, 2002: Bruss JB, Siber GR. Quantitative priming with inactivated pertussis toxoid vaccine in the aerosol challenge model. Infection and immunity. 2002; 70(8); 4600-4608. [PubMed: 12117973].

2. Cainelli et al., 2007: Cainelli Gebara VC, Risoléo L, Lopes AP, Ferreira VR, Quintilio W, Lépine F, Silva WD, Raw I. Adjuvant and immunogenic activities of the 73kDa N-terminal alpha-domain of BrkA autotransporter and Cpn60/60kDa chaperonin of Bordetella pertussis. Vaccine. 2007; 25(4); 621-629. [PubMed: 17011680].

3. Chen et al., 1998: Chen I, Finn TM, Yanqing L, Guoming Q, Rappuoli R, Pizza M. A recombinant live attenuated strain of Vibrio cholerae induces immunity against tetanus toxin and Bordetella pertussis tracheal colonization factor. Infection and immunity. 1998; 66(4); 1648-1653. [PubMed: 9529093].

4. FDA: Adacel: FDA: Adacel [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm172481.htm]

5. FDA: Boostrix: FDA: Boostrix [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm172925.htm]

6. FDA: DAPTACEL: FDA: DAPTACEL [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm101572.htm]

7. FDA: Infanrix: FDA: Infanrix [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm101568.htm]

8. FDA: KINRIX: FDA: KINRIX vaccine information [https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM241453.pdf]

9. FDA: Pediarix: FDA: Pediarix [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm146759.htm]

10. FDA: Pentacel: FDA: Pentacel [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm172502.htm]

11. FDA: Quadracel: FDA: Quadracel vaccine information [https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM439903.pdf]

12. FDA: Tripedia: FDA: Tripedia [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm101565.htm]

13. Fennelly et al., 2008: Fennelly NK, Sisti F, Higgins SC, Ross PJ, van der Heide H, Mooi FR, Boyd A, Mills KH. Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses. Infection and immunity. 2008; 76(3); 1257-1266. [PubMed: 18195025].

14. Feunou et al., 2008: Feunou PF, Ismaili J, Debrie AS, Huot L, Hot D, Raze D, Lemoine Y, Locht C. Genetic stability of the live attenuated Bordetella pertussis vaccine candidate BPZE1. Vaccine. 2008; 26(45); 5722-5727. [PubMed: 18762220].

15. GSK: Boostrix-Polio: GSK: Boostrix-Polio vaccine information [https://ca.gsk.com/media/589683/boostrix-polio.pdf]

16. GSK: Infanrix-hexa: GSK: Infanrix-hexa vaccine information [http://ca.gsk.com/media/537989/infanrix-hexa.pdf]

17. GSK: Infanrix-IPV: GSK: Infanrix-IPV vaccine information [http://ca.gsk.com/media/590851/infanrix-ipv.pdf]

18. GSK: Infanrix-IPV/Hib: GSK: Infanrix-IPV/Hib vaccine information [http://ca.gsk.com/media/590970/infanrix-ipv-hib.pdf]

19. Guiso et al., 1989: Guiso N, Rocancourt M, Szatanik M, Alonso JM. Bordetella adenylate cyclase is a virulence associated factor and an immunoprotective antigen. Microbial pathogenesis. 1989; 7(5); 373-380. [PubMed: 2622329].

20. Kamachi et al., 2003: Kamachi K, Konda T, Arakawa Y. DNA vaccine encoding pertussis toxin S1 subunit induces protection against Bordetella pertussis in mice. Vaccine. 2003; 21(31); 4609-4615. [PubMed: 14575775].

21. Kinnear et al., 2001: Kinnear SM, Marques RR, Carbonetti NH. Differential regulation of Bvg-activated virulence factors plays a role in Bordetella pertussis pathogenicity. Infection and immunity. 2001; 69(4); 1983-1993. [PubMed: 11254549].

22. Komatsu et al., 2010: Komatsu E, Yamaguchi F, Abe A, Weiss AA, Watanabe M. Synergic effect of genotype changes in pertussis toxin and pertactin on adaptation to an acellular pertussis vaccine in the murine intranasal challenge model. Clinical and vaccine immunology : CVI. 2010; 17(5); 807-812. [PubMed: 20357056].

23. Lee et al., 1999: Lee SF, March RJ, Halperin SA, Faulkner G, Gao L. Surface expression of a protective recombinant pertussis toxin S1 subunit fragment in Streptococcus gordonii. Infection and immunity. 1999; 67(3); 1511-1516. [PubMed: 10024603].

24. Merkel et al., 1998: Merkel TJ, Stibitz S, Keith JM, Leef M, Shahin R. Contribution of regulation by the bvg locus to respiratory infection of mice by Bordetella pertussis. Infection and immunity. 1998; 66(9); 4367-4373. [PubMed: 9712789].

25. Mielcarek et al., 2006: Mielcarek N, Debrie AS, Raze D, Quatannens J, Engle J, Goldman WE, Locht C. Attenuated Bordetella pertussis: new live vaccines for intranasal immunisation. Vaccine. 2006; 24 Suppl 2; S2-54-5. [PubMed: 16823926].

26. Nascimento et al., 2008: Nascimento IP, Dias WO, Quintilio W, Christ AP, Moraes JF, Vancetto MD, Ribeiro-Dos-Santos G, Raw I, Leite LC. Neonatal immunization with a single dose of recombinant BCG expressing subunit S1 from pertussis toxin induces complete protection against Bordetella pertussis intracerebral challenge. Microbes and infection / Institut Pasteur. 2008; 10(2); 198-202. [PubMed: 18248757].

27. Novotny et al., 1985: Novotny P, Chubb AP, Cownley K, Montaraz JA, Beesley JE. Bordetella adenylate cyclase: a genus specific protective antigen and virulence factor. Developments in biological standardization. 1985; 61; 27-41. [PubMed: 2872113].

28. Novotny et al., 1991: Novotny P, Chubb AP, Cownley K, Charles IG. Biologic and protective properties of the 69-kDa outer membrane protein of Bordetella pertussis: a novel formulation for an acellular pertussis vaccine. The Journal of infectious diseases. 1991; 164(1); 114-122. [PubMed: 2056199].

29. Product Monograph: Adacel-Polio: Product Monograph: Adacel-Polio vaccine information [https://www.vaccineshoppecanada.com/document.cfm?file=adacel-polio_e.pdf]

30. Product Monograph: Pediacel: Product Monograph: Pediacel vaccine information [https://www.vaccineshoppecanada.com/document.cfm?file=Pediacel_E.pdf]

31. Roberts et al., 1990: Roberts M, Maskell D, Novotny P, Dougan G. Construction and characterization in vivo of Bordetella pertussis aroA mutants. Infection and immunity. 1990; 58(3); 732-739. [PubMed: 2407655].

32. Salyers and Whitt., 2002: Abigail A. Salyers, Dixie D. Whitt. Bordetella pertussis. 263-73. Bacterial Pathogenesis: A Molecular Approach. 2002. ASM Press, Washington D.C. USA.

33. Sato and Sato, 1984: Sato H, Sato Y. Bordetella pertussis infection in mice: correlation of specific antibodies against two antigens, pertussis toxin, and filamentous hemagglutinin with mouse protectivity in an intracerebral or aerosol challenge system. Infection and immunity. 1984; 46(2); 415-421. [PubMed: 6542069].

34. Sukumar et al., 2007: Sukumar N, Mishra M, Sloan GP, Ogi T, Deora R. Differential Bvg phase-dependent regulation and combinatorial role in pathogenesis of two Bordetella paralogs, BipA and BcfA. Journal of bacteriology. 2007; 189(10); 3695-3704. [PubMed: 17351043].

35. Wiki: Bordetella pertussis: Bordetella pertussis [http://en.wikipedia.org/wiki/Bordetella_pertussis]