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Campylobacter jejuni

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
    4. Microbial Pathogenesis
    5. Host Ranges and Animal Models
    6. Host Protective Immunity
  2. Vaccine Related Pathogen Genes
    1. cadF (Protective antigen)
    2. cjaA (Protective antigen)
    3. DNA-binding protein (Protective antigen)
    4. FlaA from C. jejuni 81-176 (Protective antigen)
    5. FlaA from C. jejuni NCTC 11168 (Protective antigen)
    6. FlaC (Protective antigen)
    7. fspA1 (Protective antigen)
    8. fspA2 (Protective antigen)
    9. major outer membrane protein, MOMP (Protective antigen)
    10. peb1A (Protective antigen)
    11. PorA (Protective antigen)
    12. sodB (Protective antigen)
    13. htrA (Virmugen)
  3. Vaccine Related Host Genes
    1. IgA
    2. IgG
  4. Vaccine Information
    1. Avirulent Salmonella vaccine strain carrying C. jejuni cjaA gene
    2. C. jejuni DNA vaccine pcDNA3.1(+)-cadF
    3. C. jejuni DNA vaccine pcDNA3.1(+)-peblA
    4. C. jejuni FlaC protein vaccine
    5. C. jejuni FspA1 protein vaccine
    6. C. jejuni FspA2 protein vaccine
    7. C. jejuni MBP-FlaA protein vaccine
    8. C. jejuni PorA protein vaccine
    9. deltaphoP/Q S. typhimurium strains expressing PEB1-ss
    10. Inactivated C. jejuni whole-cell (CWC)
    11. MBP fused on Campylobacter FlaA (MBP-FlaA)
  5. References
I. General Information
1. NCBI Taxonomy ID:
197
2. Disease:
Campylobacterosis
3. Introduction
Campylobacter jejuni is a small gram-negative, microaerophilic, motile, curved-to-spiral rod that has a single polar flagellum. It can be found in the intestinal tract and oral cavity (Smibert, 1978). C. jejuni is among the most frequent causes of bacterial diarrhea worldwide and an important cause of diarrhea in travellers and deployed military personnel. It is also the infectious agent most often associated with Guillain-Barre syndrome (GBS), a postinfectin polyneuropathy, and is increasingly identified as a cause of bacteremia and a variety of systemic and localized infections in immunocompromised hosts. The bacteria is characterized by a lack of understanding of the basic virulence mechanisms and by its antigenic complexity. The LPS cores of many serotypes have been shown to contain structures which resemble human gangliosides and have been implicated in the development of autoantibodies leading to GBS, although the specific structure or structures which enable a given campylobacter strain to cause GBS are not clear (Lee et al., 1999; Pawelec et al., 2000).
4. Microbial Pathogenesis
Most Campylobacter infections are mild, self-limiting diarrheal illnesses, but severe infections do occur. The primary risk factors associated with Campylobacter infection are consuming and handling foods of animal origins, especially poultry products. In addition to epidemiological evidence, microbiological evidence supports poultry as the primary source of human Campylobacter infection (Nelson et al., 2007). The majority of Campylobacter-associated infections are thought to be sporadic cases of food poisoning; contaminated drinking water, including that from public water supplies, is the vehicle of large Campylobacter-associated outbreaks. Although Campylobacter spp. are widely distributed in the environment, the epidemiology of many cases of Campylobacter-associated infections remains unclear (Abulreesh et al., 2006). After incubation of approximately three days, abrupt cramping pain in the abdomen is followed by diarrhea. The mechanism of diarrhea induction is a complex and multifactorial process. The diarrheal stage lasts a few days. Complications are rare, but infection may be followed by the development of reactive arthritis or GBS.

Flagella-mediated motility has been shown to be necessary for Campylobacter to colonize the intestinal tract, and experimental infections in humans and animals, and in vitro analyses of adherence and invasion in cultured human cells have demonstrated that cell invasiveness is necessary in Campylobacter-induced inflammatory diarrhea. Several bacterial components have been shown to have adhesive properties (LPS, flagella, fimbrial filaments, surface-exposed proteins), and a direct role of toxins including of cytolethal distending toxin (CDT) in disease remains to be demonstrated. Host factors are of importance in the pathogenesis of GBS following a Campylobacter infection. It is now clear that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies (Engberg, 2006).
5. Host Ranges and Animal Models
The primary risk factors associated with Campylobacter infection are consuming and handling foods of animal origins, especially poultry products. In addition to epidemiological evidence, microbiological evidence supports poultry as the primary source of human Campylobacter infection (Nelson et al., 2007).
6. Host Protective Immunity
Anti-flagellar serum antibody titres of the dams did not correlate with protection of their young (Dolby et al., 1986). There was a good correlation between high campylobacter-specific IgG response and bactericidal activity. The degree of protection conferred by vaccinated dams on infant mice against colonization by Campylobacter jejuni depended on the bacterial strain, preparation, and route of administration of the vaccine. In some instances of homologous protection, serum bactericidal titres correlated well with protection. However, boiled C. jejuni vaccine, which was non-protective, also elicited a strong bactericidal antibody response. Conversely, bactericidal activity could not be demonstrated against strains capable of cross-protection. (Abimiku et al., 1989).
1. cadF
  • Gene Name : cadF
  • Sequence Strain (Species/Organism) : Campylobacter jejuni
  • VO ID : VO_0011044
  • NCBI Protein GI : WP_002851185
  • Other Database IDs : CDD:275358
    CDD:225439
    CDD:143586
  • Taxonomy ID : 194
  • Gene Strand (Orientation) : ?
  • Protein Name : fibronectin-binding outer membrane protein CadF
  • Protein pI : 5.71
  • Protein Weight : 36447.78
  • Protein Length : 419
  • Protein Note : outer membrane beta-barrel protein; TIGR04565
  • Protein Sequence : Show Sequence 
    >WP_002851185.1 MULTISPECIES: fibronectin-binding outer membrane protein CadF [Campylobacter]
MKKIFLCLGLASVLFGADNNVKFEITPTLNYNYFEGNLDMDNRYAPGIRLGYHFDDFWLDQLEFGLEHYS
DVKYTNTNKTTDITRTYLSAIKGIDVGEKFYFYGLAGGGYEDFSNAAYDNKSGGFGHYGAGVKFRLSDSL
ALRLETRDQINFNHANHNWVSTLGISFGFGGKKEKAVEEVADTRATPQAKCPVEPREGALLDENGCEKTI
SLEGHFGFDKTTINPTFQEKIKEIAKVLDENERYDTILEGHTDNIGSRAYNQKLSERRAKSVANELEKYG
VEKSRIKTVGYGQDNPRSSNDTKEGRADNRRVDAKFILR
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Chitosan-DNA vaccines were prepared by embedding pcDNA3.1(+)-cadF and pcDNA3.1(+)-peblA with chitosan respectively. The mice immunized with chitosan-DNA vaccines have generated high levels of IgA and IgG from the sera and IgA from the intestinal secretions and the P/N value went up to 20.58, 30.13 and 6.87 respectively. The chitosan-DNA vaccines induced strongest level of protection in BALB/c mice against challenge with C. jejuni HS:19 strain and the protective efficacies was 93.70 (Zheng et al., 2007).
  • Related Vaccine(s): C. jejuni DNA vaccine pcDNA3.1(+)-cadF
2. cjaA
  • Gene Name : cjaA
  • Sequence Strain (Species/Organism) : Campylobacter jejuni RM1221
  • VO ID : VO_0010955
  • NCBI Gene ID : 3231573
  • NCBI Protein GI : 1813949
  • Locus Tag : CJE1064
  • Genbank Accession : CP000025
  • Protein Accession : YP_179057
  • Other Database IDs : CDD:270412
    GOA:P94643
    InterPro: IPR001638
    UniProtKB/TrEMBL: P94643
  • Taxonomy ID : 197
  • Gene Starting Position : 993662
  • Gene Ending Position : 994501
  • Gene Strand (Orientation) : -
  • Protein Name : surface antigen, CjaA
  • Protein pI : 4.9
  • Protein Weight : 29158.88
  • Protein Length : 324
  • Protein Note : Substrate binding domain of ABC cysteine transporter; the type 2 periplasmic binding protein fold; cd13694
  • DNA Sequence : Show Sequence 
    >NC_003912.7:993662-994501 Campylobacter jejuni RM1221, complete genome
ATTAAATTTTTCCACCTTCAATCACTACATCATCAGCCTTAACATCATCTCCAAAATGAGCTTTTAAAGT
TTCATCATAAGCCTTGTGAAAAAACTGCTCTTGGCCTAGTTTAATGATCAAATTATCGATAAATTCTTTA
AGTTCTTTATCGCCTTTTTTAACCGCTGGTGCGATAACATCTTTGTTACCTAACTCTTTGATACCCATTT
TAAAATCAGGATGATCTTTCACCCAAGCAAAAAGCAAGGTATTATCATGACTTAAAGCATCGCCTCTTTT
ATCCATCAAAGCGGCAAAGGTTTCGGTATTTTGATCATATTTTAAAGTTTTAATATTAGGATAATTTTGC
GTAAAATAAGCATCTGCTGTTGTACCTTTGTTTAAAAGCAAGGTTTTATCTTTTAAATCTTCTACGCTAG
TTATATTACTATCCTTTGGTACAGCTACGCCTAAAGCTACCTTCATATAAGGCAAGCAAAAATCAACCTG
TTCTGCCCTTTGCGGAGTTTGAGTAAAATTAGCCAAAATAATATCTACTTTATTTGATTTTAAAAACTCA
ACCCTATTTGCAGCTTCAACAAGAACAAATTGCACCTTATTTTCATCGCCAAAAAGTTCTTTTGCTATGC
GTTTAGCTAAAGCTATATCATAGCCTTGATTGTTTCCTTTTTCATCTACATAACCAAAAGGTGGTTTATC
GCCAAATACCCCAATCCTAACAACTCCATTTTGCTTGATCTTATCAAGAGAATTTAAAGTTTTAGAGTCA
GAATTTCCTCCACAAGCAGCCAATACTACTGCAACAAAGGTCGTTAAAACACTTAGAAGTATTTTTTTCA
  • Protein Sequence : Show Sequence 
    >CAA71822.1 cjaA [Campylobacter jejuni]
MKKMLLSIFTTFVAVFLAACGGNSDSGASNSLERIKQDGVVRIGVFGDKPPFGYVDEKGVNQGYDIVLAK
RIAKELLGDENKVQFVLVEAANRVEFLKSNKVDIILANFTQTPERAEQVDFCLPYMKVALGVAVPQDSNI
SSIEDLKDKTLLLNKGTTADAYFTKEYPDIKTLKYDQNTETFAALIDQRGDALSHDNTLLFAWVKEHPEF
KMAIKELGNKDVIAPAVKKGDKELKEFIDNLITKLGEEQFFHKAYDETLKSHFGDDVKADDVVIEGGKI
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : A total of 840 Light Sussex chickens were used to evaluate a Salmonella enterica serovar Typhimurium DeltaaroA vaccine expressing the C. jejuni amino acid binding protein CjaA. Chickens were given the vaccine at 1-day-old and two weeks later by oral gavage, then challenged after a further two weeks with C. jejuni. Across six biological replicates, statistically significant reductions in caecal C. jejuni of c. 1.4log(10) colony-forming units/g were observed at three and four weeks post-challenge relative to age-matched unvaccinated birds. Protection was associated with the induction of CjaA-specific serum IgY and biliary IgA (Buckley et al., 2010).
  • Related Vaccine(s): Avirulent Salmonella vaccine strain carrying C. jejuni cjaA gene
3. DNA-binding protein
  • Gene Name : DNA-binding protein
  • Sequence Strain (Species/Organism) : Campylobacter jejuni
  • NCBI Protein GI : WP_002867076
  • Other Database IDs : CDD:223854
    CDD:153102
  • Taxonomy ID : 197
  • Gene Strand (Orientation) : ?
  • Protein Name : DNA starvation/stationary phase protection protein
  • Protein pI : 5.06
  • Protein Weight : 17254.47
  • Protein Length : 243
  • Protein Note : DNA-binding ferritin-like protein (oxidative damage protectant) [Inorganic ion transport and metabolism, Defense mechanisms]; COG0783
  • Protein Sequence : Show Sequence 
    >WP_002867076.1 DNA starvation/stationary phase protection protein [Campylobacter jejuni]
MSVTKQLLQMQADAHHLWVKFHNYHWNVKGLQFFSIHEYTEKAYEEMAELFDSCAERVLQLGEKAITCQK
VLMENAKSPKVAKDCFTPLEVIELIKQDYEYLLAEFKKLNEEAEKESDTTTAAFAQENIAKYEKSLWMIG
ATLQGACKM
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Theoret et al., 2012)
4. FlaA from C. jejuni 81-176
  • Gene Name : FlaA from C. jejuni 81-176
  • Sequence Strain (Species/Organism) : Campylobacter jejuni subsp. jejuni 81-176
  • VO ID : VO_0011046
  • NCBI Gene ID : 4682159
  • NCBI Protein GI : 121612545
  • Locus Tag : CJJ81176_1339
  • Genbank Accession : AY102622
  • Protein Accession : YP_001000997
  • Taxonomy ID : 354242
  • Gene Starting Position : 1255199
  • Gene Ending Position : 1256929
  • Gene Strand (Orientation) : -
  • Protein Name : flagellin
  • Protein pI : 5.37
  • Protein Weight : 56366.68
  • Protein Length : 576
  • Protein Note : FlaA; structural flagella protein; in Helicobacter the flagella are composed of flagellin A and flagellin B; the amounts of each seem to be controlled by environmental conditions
  • DNA Sequence : Show Sequence 
    >NC_008787.1:1255199-1256929 Campylobacter jejuni subsp. jejuni 81-176, complete genome
ACTATTGTAATAATCTTAAAACATTTTGCTGACTAGAATTTGCTTGAGCCATTGCATAAGAACCACTTTG
GGCTAAGATGTTAGCTTTAGAGTAGTTTGCACTCTCACTTGCAAAGTCTACATCTCTGATTTGCGATTCT
GCTGCTTTAACATTAACTTGAGTTACAGTAATGTTATTTATAGTTGATGTAACTTGATTTTGTATAGAAC
CAATATCTGCTCTGATTTGATCTAGATTTGTTATAGCAGTTTCTGCTATATCCATAACCGCCATTGCACC
TTTAAGAGTGGTTACACCTGCAGTCTCATCAGTTGTATTAGCAGCAGTAGTTTTAAGGGCTGCAAATTGA
GAATTTCCTGAGCCAGAAGAAAATCCTGAACCTGCTGAAACAACATAAGTATTGCTCATTGAAGCCGCAC
TTGAAATAATTTGTATTCCTTGACTCAATCCAACAGATAAATTTTTACCACTACCCACAGAAAATCCTGA
ACCTCTAGAAAATCCTGAACCTTGTGCACTCATAAATGCAGAAATTGAACTTACATTTTGAGTAAAAACA
AATTTTCCACCACCTTTATAAGAATTAAATCCCATAGCATCGGCATTGGTTGCTGAAATTTGACCTTTTG
ATTCTCTTAAAGACACTGAAGATTGAGAAATCATATCTGTTGTACCCATACCTATAGCACTAAGATTGGT
TCCACTTATATTGATATCTCTACCATCATTTTTAACTAAAGATAATCGCCCATAGTTTTCTTTTTGATTT
GCCAAAATACCAGAACCAACACCTATATCTCCAGTAATTTTAATACCCCTGCCATCAGCCGATGTAAGAA
CAAGCTTGCCGTTTTCATCTTTAGAAGCTTGAACTCCTGTGGTATCTTTAACCGCATTGATAGCTGAAAT
CAAAGAGCCGTTACCATCTCCGTCTTTGTATTCAATTTTTCCTATAGTTACTCCATTAATGGCAAATTCT
TGAGAAGTAGTTCCTTCTTTTATAGCATAAACGCCAGTTGTTTTTACATCGTAAGTTGCGCGAACTCCTG
TTTTATCAGCGCTTTTATTGATCTCTTCAGCCAAAGCTCCAAGTCCTGTTCCAACTGAAGTTGAAATCAC
AACATTATCAAATTTAAAATCTTCTATACCATTGTAGTTTTTAATAGTAAGACCAACCACACCTGAAGTA
AAACTTTGAGCACCGGTTTCAAATCTTGTAACACCGATTTTAGAAGATTGAGTAGCACCGATAGTTGCTT
TCACAGTTTGGTTTGAACTTGCGCCGATTTGGAATTCTTGATTGGTAAAATTTCCACTTAAAAGTTGCTT
ACCATTAAATGAAGTAGTATTTGCGATATTATCAAGCTCTTCCATTAATTTATTAATATCTGCTTGAAGC
ATAGTTCTTGTTTTTAAACTTTGTCCATCTTGAGCTGCTTGAGTAGCTTTAGTCTTGATAGTATCAAGAA
TTTTTAATTGCTCATCCATAGCTTTATCTGCGGTTTGTAAGATACCTAAAGCATCATTACCATTTGATAT
AGCTTGACCTAAAGTATTTGCTTGAGATCTTAAGCTATCTGCTATCGCCATCCCTGAAGCATCATCTGCT
GCTGAGTTAATTCTAAGACCTGAACTAAGTCTGCTTAAAGAAGCATCTAAACTTTTAGCATTAAGATCAG
AGTTTGCTTTTGCATTCAATGCTGCAACATTTGTGTTAATACGAAATCCCA
  • Protein Sequence : Show Sequence 
    >YP_001000997.1 flagellin [Campylobacter jejuni subsp. jejuni 81-176]
MGFRINTNVAALNAKANSDLNAKSLDASLSRLSSGLRINSAADDASGMAIADSLRSQANTLGQAISNGND
ALGILQTADKAMDEQLKILDTIKTKATQAAQDGQSLKTRTMLQADINKLMEELDNIANTTSFNGKQLLSG
NFTNQEFQIGASSNQTVKATIGATQSSKIGVTRFETGAQSFTSGVVGLTIKNYNGIEDFKFDNVVISTSV
GTGLGALAEEINKSADKTGVRATYDVKTTGVYAIKEGTTSQEFAINGVTIGKIEYKDGDGNGSLISAINA
VKDTTGVQASKDENGKLVLTSADGRGIKITGDIGVGSGILANQKENYGRLSLVKNDGRDINISGTNLSAI
GMGTTDMISQSSVSLRESKGQISATNADAMGFNSYKGGGKFVFTQNVSSISAFMSAQGSGFSRGSGFSVG
SGKNLSVGLSQGIQIISSAASMSNTYVVSAGSGFSSGSGNSQFAALKTTAANTTDETAGVTTLKGAMAVM
DIAETAITNLDQIRADIGSIQNQVTSTINNITVTQVNVKAAESQIRDVDFASESANYSKANILAQSGSYA
MAQANSSQQNVLRLLQ
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Mice were immunized intranasally with two doses of 3 to 50 microgram of MBP-FlaA. The protective efficacies of a 50 microgram of MBP-FlaA plus LT(R192G) dose against disease symptoms and intestinal colonization were 81.1 and 84%, respectively. When mice which had been immunized with 50 microgram of MBP-FlaA plus LT(R192G) intranasally were challenged orally with 8 x 10(10), 8 x 10(9), or 8 x 10(8) cells of strain 81-176, the protective efficacies against intestinal colonization at 7 days postinfection were 71.4, 71.4, and 100%, respectively (Lee et al., 1999).
  • Related Vaccine(s): C. jejuni MBP-FlaA protein vaccine
5. FlaA from C. jejuni NCTC 11168
  • Gene Name : FlaA from C. jejuni NCTC 11168
  • Sequence Strain (Species/Organism) : Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819
  • VO ID : VO_0010942
  • NCBI Gene ID : 905631
  • NCBI Protein GI : 218562948
  • Locus Tag : Cj1339c
  • Genbank Accession : AL111168
  • Protein Accession : YP_002344727
  • Other Database IDs : BioCyc: CJEJ192222:CJ1339C-MONOMER
    EMBL: AL139078
    InterPro: IPR001029
    InterPro: IPR001492
    InterPro: IPR010810
    KEGG: cje:Cj1339c
    Pfam: PF00669
    Pfam: PF00700
    Pfam: PF07196
    PIR: H81277
    PRINTS: PR00207
    ProDom: PD000316
    UniProt: P56963
  • Taxonomy ID : 192222
  • Gene Starting Position : 1269231
  • Gene Ending Position : 1270949
  • Gene Strand (Orientation) : -
  • Protein Name : flagellin A
  • Protein pI : 5.36
  • Protein Weight : 55763.1
  • Protein Length : 572
  • Protein Note : flaA, flagellin A, len: 572 aa; 80.7% identity to FLAA_CAMJE flagellin A (575 aa), fasta scores; opt: 2816 z-score: 2717.6 E(): 0, 80.7% identity in 575 aa overlap. 48.3% identity to HP0601. Also similar to Cj1338c (flaA), Cj0720c flaC (24.5% identity in 220 aa overlap), and Cj0887c flaD (20.2% identity in 560 aa overlap). Contains fam match to entry PF00669 Flagellin_N, Bacterial flagellin N-terminus, and Pfam match to entry PF00700 Flagellin_C, Bacterial flagellin C-terminus. The flaA and flaB genes have a GC content of 37% compared to the overall genome GC content of 30.5%
  • Protein Annotation : FUNCTION: Flagellin is the subunit protein which polymerizes to form the filaments of bacterial flagella (UniProt: P56963)

    SUBUNIT: Heteropolymer of flaA and flaB (UniProt: P56963)

    SIMILARITY: Belongs to the bacterial flagellin family (UniProt: P56963)
  • DNA Sequence : Show Sequence 
    >NC_002163.1:1269231-1270949 Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819 chromosome, complete genome
ACTACTGTAGTAATCTTAAAACATTTTGTTGAACAGAATTAGCCTGTGCCATGGCATAAGAGCCGCTTTG
AGCTAAGATATTTGCTTTAGAGTAGTTTGCACTCTCGGCTGCAAAGTCTACATCACGGATTTGCGATTCT
GCTGCTTTAACGTTTACTTGAGTTACGGTGATGTTGTTTATAGTTGATGTAACTTGATTTTGTACCGAAC
CAATGTCGGCTCTGATTTGATCAAGATTTGTTATAGCTGTTTCAGCTATATCCATCACAGCCATAGCGCC
TTTAAGTGTGGTAACACCTGCTGTTTCATCTTTTACTCCAAAAGCAGTTGTTTTCATAGTTGCAAACTGA
GAAAGTGTTGAACCACTTGAAAAACCTGAGCCTGCAGAAACATTATATACCGTAGAAAGTTGCGAAGCAG
CTGAAATAGCTATAGCGTTTGCAAAACCTGTGGAATAATTTTTACCGCTACCTACAGAATAACCTGAACC
TGAAGAAAATCCACTTCCTGCGCTACTCATATAGGCACTAACAGAAGAATAACCACCTAACACAACTCCT
TTGTTTGCAGAACCAAATCCCATAGCATCAGCGATATTAGCATCAATTTGTCCTTTTGACTCTCTTAAAG
AAACAGAAGCTTGAGAGATAAATTGAGTTGCACCAAAACCTGCAGAAGAAAGATTGCTACCGCTGATTAA
AATATCTTTACCATCATTTTTAACTAAAGACAAGCGGCCATAGTTTTCTTTCATATCAGCATTGATAAAG
GCACCTCCACCTATATTACCATCGATTTTAATCCCTCTACCTTCTCTTGAAGTAAGTAAAAGTTGTCCAT
TAGCATCGATCGAAGCTTCAACTCCAGTGGTATCTTTAACCGAATTGATTGCAGCAACTAAGGCTCCATT
AGCATCACCATCTTTGTAATCTACTTTACCGATTTTTACCCCATTGATAGCAAAAGTATCTGAAGTAGCT
CCTGCTCTAACTGCAGCTATACCTCTAGTTTCTACTGTAAAAGTAGCTCTAACACCTGTTTTATCAGCAT
TTTTATTGATCTCATCTGCTAAAGCTCCAAGTCCTGTTCCAACTGAAGTTGAAATCACAACTTTTTGAAA
CTGAAAATCATCTATACCATTGTAATTTTTAAGAGTAAATTGTACTTCGCCACTAGTTGAAATTCTTCCT
CCTGTTTCAAAGCGTGTTAAACCTATCTTAGAAGATTGAGTTGCTCCTATAGTAGCTTTTACAGTTTGAT
TTGAACTTGCACCGATTTGAAATTCTTGATTGATAAAATTCCCACTTAAAAGTTGTTTACCGTTAAATGA
AGTAGTATTTGCAATATTGTCAAGTTCTTCCATTAAACGGTTGATATCTGCTTGAAGCATGGTTCTTGTT
TTTAAACTTTGTCCATCTTGAGCCGCTTGAGTTGCCTTAGTTTTGATTGTATCTAAGATTTTAAGTTGCT
CATCCATAGCCTTATCAGCAGTTTGTAAGATACCTAAAGCATCATTACCATTAGATATAGCTTGACCTAA
AGTATTAGCTTGAGATCTTAAACTATCTGCTATCGCCATCCCTGAAGCATCATCTGCTGCGGAGTTGATT
CTAAGACCTGAACTAAGTCTGCTTAAAGAAGCATCTAAACTTTTACTATTTAAATCAGCGTTTGCTTTTG
CATTTAAAGCTGCAACATTGGTGTTAATACGAAATCCCA
  • Protein Sequence : Show Sequence 
    >YP_002344727.1 flagellin A [Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819]
MGFRINTNVAALNAKANADLNSKSLDASLSRLSSGLRINSAADDASGMAIADSLRSQANTLGQAISNGND
ALGILQTADKAMDEQLKILDTIKTKATQAAQDGQSLKTRTMLQADINRLMEELDNIANTTSFNGKQLLSG
NFINQEFQIGASSNQTVKATIGATQSSKIGLTRFETGGRISTSGEVQFTLKNYNGIDDFQFQKVVISTSV
GTGLGALADEINKNADKTGVRATFTVETRGIAAVRAGATSDTFAINGVKIGKVDYKDGDANGALVAAINS
VKDTTGVEASIDANGQLLLTSREGRGIKIDGNIGGGAFINADMKENYGRLSLVKNDGKDILISGSNLSSA
GFGATQFISQASVSLRESKGQIDANIADAMGFGSANKGVVLGGYSSVSAYMSSAGSGFSSGSGYSVGSGK
NYSTGFANAIAISAASQLSTVYNVSAGSGFSSGSTLSQFATMKTTAFGVKDETAGVTTLKGAMAVMDIAE
TAITNLDQIRADIGSVQNQVTSTINNITVTQVNVKAAESQIRDVDFAAESANYSKANILAQSGSYAMAQA
NSVQQNVLRLLQ
  • Molecule Role : Protective antigen
  • Related Vaccine(s): MBP fused on Campylobacter FlaA (MBP-FlaA)
6. FlaC
  • Gene Name : FlaC
  • Sequence Strain (Species/Organism) : Campylobacter jejuni subsp. jejuni 81-176
  • VO ID : VO_0011048
  • NCBI Gene ID : 4682885
  • NCBI Protein GI : 121612344
  • Locus Tag : CJJ81176_0743
  • Genbank Accession : CP000538
  • Protein Accession : YP_001000416
  • Taxonomy ID : 354242
  • Gene Starting Position : 671962
  • Gene Ending Position : 672711
  • Gene Strand (Orientation) : -
  • Protein Name : flagellin subunit protein FlaC
  • Protein pI : 4.32
  • Protein Weight : 25481.71
  • Protein Length : 249
  • Protein Note : identified by match to protein family HMM PF00669
  • DNA Sequence : Show Sequence 
    >NC_008787.1:671962-672711 Campylobacter jejuni subsp. jejuni 81-176, complete genome
ATTATTGTAATAAATTAGCAATTTTGCTTTGAAGCTGCATGTTGGATTGCGCAGCAACAAAAGCAGCAGC
ATTTTCTTTTAGATAATTGGCATTAAAATCATTAACATTTTTTGCCATATCATTATTTAGTAAATTATTT
TCAGCTGCTTTTGAGTTGATGCTATTTTGAACACTTGCATTAATATTTGATGTAATGGCATTGATACCTG
AACCTATTTCACTTCTTAAACTTCCAAGTTGATCCATAAAATTTGTAATACTATCTTGATTATCTATGCT
TAATCCACCTGTTGCTAATGGATTTAAATTTGTAGTTTCAGTTCCGCTACCTACTACAAAATTCATAGTT
TGAAAGACATTTTTTCCATTATAAGTTGCATTATTAAAAGAATTATTGATGGATTCTTGTATGCGTGTTG
CTTCTGTTCTTAGCATTCCTTTTTGAGAATCATTAAGTGCAGCATTGTTCATTTTTACTGAAAGTTCATT
AAGTCTATCTGCGCTTTGAGAGATATTGGTAAGGCTAGCATCTGCAATTTGTAAAACCCCTATAGCATCA
TAAGCATTTGCGACACCTTGATCTATAGTGCTTGATTGAGATCTTAAAGAATCAGCAATAGCTAAATTAG
CACTATCAACTCCACTTATTGCGCGAACAGCTGCAATATTTTCTAAAGCTTTATCGCTAGCTTTTTGTGC
ATTATTTAAATAATAATTTTGTTGCATCATAGTTGCATCAGAGATCATCA
  • Protein Sequence : Show Sequence 
    >YP_001000416.1 flagellin subunit protein FlaC [Campylobacter jejuni subsp. jejuni 81-176]
MMISDATMMQQNYYLNNAQKASDKALENIAAVRAISGVDSANLAIADSLRSQSSTIDQGVANAYDAIGVL
QIADASLTNISQSADRLNELSVKMNNAALNDSQKGMLRTEATRIQESINNSFNNATYNGKNVFQTMNFVV
GSGTETTNLNPLATGGLSIDNQDSITNFMDQLGSLRSEIGSGINAITSNINASVQNSINSKAAENNLLNN
DMAKNVNDFNANYLKENAAAFVAAQSNMQLQSKIANLLQ
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Immunogenicity and protective efficacy of three Campylobacter jejuni flagellum-secreted proteins, FlaC, FspA1, and FspA2, were compared by use of a mouse model. All three proteins were immunogenic, FlaC provided an 18% protection against disease from C. jejuni 81-176 (Baqar et al., 2008).
  • Related Vaccine(s): C. jejuni FlaC protein vaccine
7. fspA1
  • Gene Name : fspA1
  • Sequence Strain (Species/Organism) : Campylobacter jejuni
  • VO ID : VO_0011047
  • NCBI Protein GI : 116292649
  • Other Database IDs : CDD:330552
  • Taxonomy ID : 197
  • Gene Strand (Orientation) : -
  • Protein Name : FspA1
  • Protein pI : 4.34
  • Protein Weight : 15410.38
  • Protein Length : 187
  • Protein Note : exonuclease subunit SbcC; Provisional; cl25731
  • Protein Sequence : Show Sequence 
    >ABJ97640.1 FspA1 [Campylobacter jejuni]
MQINNSLNSLSQYVKVNSNEENQNSKNQEQNALAQDPAVEVNISKEAKEKSNASNQNNSQAPAQALNAQN
NTQQDSSSNSEDKLTELTQKLAEIQAKIVELTAKMSKANEDQIKSIESQIATLNAQASTIQAQIQELQSQ
QA
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Immunogenicity and protective efficacy of three Campylobacter jejuni flagellum-secreted proteins, FlaC, FspA1, and FspA2, were compared by use of a mouse model. Immunization with FspA1 resulted in 57.8% protection without adjuvant or 63.8% protection with adjuvant against homologous challenge with 81-176 (Baqar et al., 2008).
  • Related Vaccine(s): C. jejuni FspA1 protein vaccine
8. fspA2
  • Gene Name : fspA2
  • Sequence Strain (Species/Organism) : Campylobacter jejuni
  • VO ID : VO_0011049
  • NCBI Protein GI : 116292677
  • Taxonomy ID : 197
  • Gene Strand (Orientation) : ?
  • Protein Name : FspA2
  • Protein pI : 5.78
  • Protein Weight : 15654.3
  • Protein Length : 187
  • Protein Note : sigma 28 regulated; Campylobacter jejuni-specific virulence factor that is secreted through the flagella filament
  • Protein Sequence : Show Sequence 
    >ABJ97654.1 FspA2 [Campylobacter jejuni]
MKIDTLTKNFSNYQTQINKNNDLASNVHSDNVVKIQISDEARSLSQANSKNEKEYEIKVSQEKIENHKDQ
NSIQSSKGGGNPALEALIAKLAEILAKIAELTQKMTNANEQMKTTFQKQIDVLISQADVIQAQIQELQSQ
QA
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Immunogenicity and protective efficacy of three Campylobacter jejuni flagellum-secreted proteins, FlaC, FspA1, and FspA2, were compared by use of a mouse model. Immunization with FspA2 provided 38.4% (without adjuvant) or 47.2% (with adjuvant) protection against disease from homologous challenge with CG8486 (Baqar et al., 2008).
  • Related Vaccine(s): C. jejuni FspA2 protein vaccine
9. htrA
  • Gene Name : htrA
  • Sequence Strain (Species/Organism) : Campylobacter jejuni
  • NCBI Protein GI : CAA57948
  • Other Database IDs : CDD:273938
    CDD:290102
    CDD:238487
    GOA:Q46120
    HSSP: 1KY9
    InterPro: IPR001254
    InterPro: IPR001478
    InterPro: IPR001940
    InterPro: IPR009003
    InterPro: IPR011782
    UniProtKB/TrEMBL: Q46120
  • Taxonomy ID : 197
  • Protein Name : serine protease
  • Protein pI : 9.23
  • Protein Weight : 48014.35
  • Protein Length : 531
  • Protein Note : periplasmic serine protease, Do/DeqQ family; TIGR02037
  • Protein Sequence : Show Sequence 
    >CAA57948.1 serine protease [Campylobacter jejuni]
MKKIFLSLSLASALFAASINFNESTATANRVNPAAGNAVLSYHDSIKDAKKSVVNISTSKTITRANRPSP
LDDFFNDPYFKQFFDFDFPQRKGKNDKEVVSSLGSGVIISKDGYIVTNNHVVDDADTITVNLPGSDIEYK
AKLIGKDPKTDLAVIKIEANNLSAITFTNSDDLMEGDVVFALGNPFGVGFSVTSGIISALNKDNIGLNQY
ENFIQTDASINPGNSGGALVDSRGYLVGINSAILSRGGGNNGIGFAIPSNMVKDIAKKLIEKGKIDRGFL
GASILALQGDTKKAYKNQEGALITDVQKGSSADEAGLKRGDLVTKVNDKVIKSPIDLKNYIGTLEIGQKI
SLSYERDGENKQASFILKGEKENPKGVQSDLIDGLSLRNLDPRLKDRLQIPKDVNGVLVDSVKEKSKGKN
SGFQEGDIIIGVGQSEIKNLKDLEQALKQVNKKEFTKVWVYRNGLATLLVLK
  • Molecule Role : Virmugen
  • Molecule Role Annotation : Moreover, ΔhtrA mutant infected mice displayed lower apoptotic cell numbers in the large intestinal mucosa, less colonic accumulation of neutrophils, macrophages and monocytes, lower large intestinal nitric oxide, IFN-γ, and IL-6 as well as lower TNF-α and IL-6 serum concentrations as compared to WT strain infected mice at day 6 p.i.(Heimesaat et al., 2014)
10. major outer membrane protein, MOMP
  • Gene Name : major outer membrane protein, MOMP
  • Sequence Strain (Species/Organism) : Campylobacter jejuni
  • NCBI Protein GI : WP_002910950
  • Other Database IDs : CDD:328846
  • Taxonomy ID : 197
  • Gene Strand (Orientation) : ?
  • Protein Name : major outer membrane protein
  • Protein pI : 4.37
  • Protein Weight : 42068.56
  • Protein Length : 493
  • Protein Note : outer membrane porin, OprD family; cl21675
  • Protein Sequence : Show Sequence 
    >WP_002910950.1 major outer membrane protein [Campylobacter jejuni]
MKLVKLSLVAALAAGAFSAANATPLEEAIKDVDVSGVLRYRYDTGTFDKNWGTPNSNLNDSKQDHKYRAQ
VNFSAAIADNFKAFVQFDYNAVDGGTGVDNATNAQKGFFVRQLYLTYTNEDVATSVIAGKQQLNIIWTDN
GIDGLVGTGVKVVNNSIDGLTLAAFAVDSFMATEQGSDLVGHNGSQFNPDSIGNLYGAAAVGSYDLAGGQ
FNPQLWLAYWDQVAFFYALDASYSTTIFDGINWTLEGAYLGNSVDSDLDSARYANGNLFALKGSIEVNGW
DASLGGLYYGDKEKASTVVIEDQGNLGSLLAGEEIFYTTGSRLNGDTGRNIFGYVTGGYTFNETVRVGAD
FVYGGTKTEAANHLGGGKKLEAVARVDYKYSPKLNFSAFYSYVNLDQGVNTNESADHSTVRLQALYKF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : These observations provide direct evidence for conformation-dependent humoral responses to MOMP induced by Campylobacter infection (Huang et al., 2007)
11. peb1A
  • Gene Name : peb1A
  • Sequence Strain (Species/Organism) : Campylobacter jejuni
  • VO ID : VO_0011045
  • NCBI Protein GI : 112360246
  • 3D structure: PDB ID : 2V25
  • Other Database IDs : CDD:183381
    EnsemblGenomes-Gn:Cj0921c
    EnsemblGenomes-Tr:CAL35041
    GOA:Q0P9X8
    InterPro: IPR001638
    InterPro: IPR018313
    PDB: 2V25
  • Taxonomy ID : 192222
  • Gene Strand (Orientation) : ?
  • Protein Name : aspartate/glutamate-binding ABC transporter protein
  • Protein pI : 8.53
  • Protein Weight : 27458.45
  • Protein Length : 390
  • Protein Note : bifunctional adhesin/ABC transporter aspartate/glutamate-binding protein; Reviewed
  • Protein Sequence : Show Sequence 
    >CAL35041.1 aspartate/glutamate-binding ABC transporter protein [Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819]
MVFRKSLLKLAVFALGACVAFSNANAAEGKLESIKSKGQLIVGVKNDVPHYALLDQATGEIKGFEVDVAK
LLAKSILGDDKKIKLVAVNAKTRGPLLDNGSVDAVIATFTITPERKRIYNFSEPYYQDAIGLLVLKEKKY
KSLADMKGANIGVAQAATTKKAIGEAAKKIGIDVKFSEFPDYPSIKAALDAKRVDAFSVDKSILLGYVDD
KSEILPDSFEPQSYGIVTKKDDPAFAKYVDDFVKEHKNEIDALAKKWGL
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Chitosan-DNA vaccines were prepared by embedding pcDNA3.1(+)-cadF and pcDNA3.1(+)-peblA with chitosan respectively. The mice immunized with chitosan-DNA vaccines have generated high levels of IgA and IgG from the sera and IgA from the intestinal secretions and the P/N value went up to 20.58, 30.13 and 6.87 respectively. The chitosan-DNA vaccines induced strongest level of protection in BALB/c mice against challenge with C. jejuni HS:19 strain and the protective efficacies was 93.70 (Zheng et al., 2007).
  • Related Vaccine(s): C. jejuni DNA vaccine pcDNA3.1(+)-peblA
12. PorA
  • Gene Name : PorA
  • Sequence Strain (Species/Organism) : Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819
  • NCBI Gene ID : 905550
  • NCBI Protein GI : 218562871
  • Locus Tag : Cj1259
  • Genbank Accession : AL111168
  • Protein Accession : YP_002344650
  • Taxonomy ID : 192222
  • Gene Starting Position : 1189120
  • Gene Ending Position : 1190394
  • Gene Strand (Orientation) : +
  • Protein Name : major outer membrane protein
  • Protein pI : 4.49
  • Protein Weight : 42413
  • Protein Length : 424
  • Protein Note : Original (2000) note: Cj1259, porA, major outer membrane protein (MOMP), len: 424 aa; 94.6% identical to TR:AAC82317 (EMBL: U96452) C. jejuni major outer membrane porin (424 aa), and 98.0% identity to MOMP_CAMJE major outer membrane protein (fragments) (399 aa). No hp match. Also simlar in part to Cj1021c (63 aa, 34.5% identity in 55 aa overlap)~Updated (2006) note: Pfam domain PF05538 Campylobacter major outer membrane protein identified within CDS. Further support given to product function. Characterised within Campylobacter jejuni, so putative not added to product function. Functional classification -Membranes, lipoproteins and porins~PMID:7543469, PMID:9163918
  • DNA Sequence : Show Sequence 
    >NC_002163.1:1189120-1190394 Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819 chromosome, complete genome
CATGAAACTAGTTAAACTTAGTTTAGTTGCAGCTCTTGCTGCAGGTGCTTTTTCAGCAGCTAACGCTACT
CCACTTGAAGAAGCGATCAAAGATGTTGATGTATCAGGTGTATTAAGATACAGATACGATACAGGTAATT
TTGATAAAAATTTCGTTAACAACTCAAATTTAAACAACAGCAAACAAGATCACAAATATAGAGCACAAGT
TAACTTCAGTGCTGCTATAGCTGATAACTTCAAAGCTTTTGTTCAATTTGACTATAATGCTGCTGATGGT
GGTTATGGTGCTAATGGAATAAAAAATGATCAAAAAGGACTTTTTGTTCGTCAATTATACTTAACTTATA
CAAATGAAGATGTTGCTACAAGTGTAATCGCTGGTAAACAACAATTAAACCTTATCTGGACGGATAACGC
TATTGATGGTTTAGTTGGCACAGGTGTTAAAGTAGTAAATAACAGCATCGATGGTTTAACTCTAGCTGCT
TTTGCTGTAGATAGCTTCATGGCTGCAGAGCAAGGTGCAGATTTATTAGAACATAGTAATATTTCAACAA
CATCAAATCAAGCTCCTTTTAAAGTAGATTCAGTAGGAAATCTTTACGGTGCTGCTGCTGTAGGTTCTTA
TGATCTTGCTGGTGGACAATTCAACCCACAATTATGGTTAGCTTATTGGGATCAAGTAGCATTCTTCTAT
GCTGTAGATGCAGCTTATAGTACAACTATCTTTGATGGAATCAACTGGACACTTGAAGGTGCTTACTTAG
GAAATAGCCTTGATAGCGAACTTGATGATAAAACACACGCTAATGGCAATTTATTTGCTTTAAAAGGTAG
CATTGAAGTAAATGGTTGGGATGCTAGCCTTGGTGGTTTATACTACGGTGATAAAGAAAAAGCTTCTACA
GTTGTAATCGAAGATCAAGGTAATCTTGGTTCTTTACTTGCAGGTGAGGAAATTTTCTATACTACTGGTT
CAAGACTAAATGGTGATACTGGTAGAAATATCTTCGGTTATGTAACTGGTGGATATACTTTCAACGAAAC
AGTTCGCGTTGGTGCTGACTTCGTATATGGTGGAACAAAAACAGAAGCTGCTAATCATTTAGGTGGTGGT
AAAAAACTTGAAGCTGTTGCAAGAGTAGATTACAAATACTCTCCAAAACTTAACTTCTCAGCATTCTATT
CTTATGTGAACCTAGATCAAGGTGTAAACACTAATGAAAGTGCTGATCATAGCACTGTAAGACTTCAAGC
TCTTTACAAATTCTA
  • Protein Sequence : Show Sequence 
    >YP_002344650.1 major outer membrane protein [Campylobacter jejuni subsp. jejuni NCTC 11168 = ATCC 700819]
MKLVKLSLVAALAAGAFSAANATPLEEAIKDVDVSGVLRYRYDTGNFDKNFVNNSNLNNSKQDHKYRAQV
NFSAAIADNFKAFVQFDYNAADGGYGANGIKNDQKGLFVRQLYLTYTNEDVATSVIAGKQQLNLIWTDNA
IDGLVGTGVKVVNNSIDGLTLAAFAVDSFMAAEQGADLLEHSNISTTSNQAPFKVDSVGNLYGAAAVGSY
DLAGGQFNPQLWLAYWDQVAFFYAVDAAYSTTIFDGINWTLEGAYLGNSLDSELDDKTHANGNLFALKGS
IEVNGWDASLGGLYYGDKEKASTVVIEDQGNLGSLLAGEEIFYTTGSRLNGDTGRNIFGYVTGGYTFNET
VRVGADFVYGGTKTEAANHLGGGKKLEAVARVDYKYSPKLNFSAFYSYVNLDQGVNTNESADHSTVRLQA
LYKF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Adult BALB/c mice were orally immunized with a recombinant glutathione S-transferase (GST) fused to PorA prepared from Campylobacter jejuni C31 (O:6,7) (GST-PorA) combined with a modified heat-labile enterotoxin of Escherichia coli as an adjuvant and later orally challenged with C31 strain or three heterologous strains: 48 (O:19), 75 (O:3), and 111 (O:1,44). The vaccine produced robust antibody responses against both antigens in serum and secretion. Since strain C31 was a poor colonizer, homologous protection could not be studied. The protective efficacies of heterologous strains were 43% (for strain 48, P < 0.001), 29% (for strain 75, P < 0.005), and 42% (for strain 111, P < 0.001) for the 9-day period compared to control mice given phosphate-buffered saline. Thus, PorA provided appreciable protection against colonization with heterologous serotypes(Islam et al., 2010)
  • Related Vaccine(s): C. jejuni PorA protein vaccine
13. sodB
  • Gene Name : sodB
  • Sequence Strain (Species/Organism) : Campylobacter jejuni
  • NCBI Protein GI : AIJ27548
  • Other Database IDs : CDD:223678
  • Taxonomy ID : 197
  • Protein Name : superoxide dismutase
  • Protein pI : 6.23
  • Protein Weight : 23611.45
  • Protein Length : 281
  • Protein Note : Superoxide dismutase [Inorganic ion transport and metabolism]; COG0605
  • Protein Sequence : Show Sequence 
    >AIJ27548.1 superoxide dismutase [Campylobacter jejuni]
MFELRKLPYDTNAFGDFLSAETFSYHHGKHHNTYVTNLNNLIKDTEFAGKDLVSIIKTSNGGVFNNAAQV
YNHDFYFDCIKPSTGCGCGGSCQSIDANLQAALEKEFGSLENFKAEFIKGATGVFGSGWFWLVYNTKNQK
LEFVGTSNAATPITEDKVPLLVVDVWEHAYYVDHRNARPAYLEKFYAHINWEFVAKAYEWALKEGMGSVS
FYANELHPVK
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Superoxide dismutase SodB is a protective antigen against Campylobacter jejuni colonisation in chickens(Chintoan-Uta et al., 2015)
1. IgA
  • Gene Name : IgA
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 238447
  • Genbank Accession : AC160982
  • Taxonomy ID : 10090
  • Chromosome No : 12
  • Gene Starting Position : 8607
  • Gene Ending Position : 12639
  • Gene Strand (Orientation) : -
  • Protein Name : immunoglobulin heavy constant alpha
  • Protein Note : Also known as IgA; Igh-2
  • DNA Sequence : Show Sequence 
    >gi|121699722:8607-12639 Mus musculus immunoglobulin heavy chain complex (Igh) on chromosome 12
AGTACTGGGGGACCTCTTTGCTGCCAAACGGGCCTCGAACAGTTGTAACAGTGAGTGCTGTGCTGTAGAA
CAAGCTCAGTAGGAAGAGGGTGAGGAAGGTCACAGTGGTGGGCCACAGGCTGGCACCTGGGGCCTCTTCC
TCCAGGATGTCTTCTGACTGGTCCAGTAGCACATAGGAAAGTGGCTCTTGACGTTCTGTAAGACATAGAT
GACCTTCTAGATCCAAACCCATGGGGATGGGGGCTCAGACTTAAGGTTTCTGCTTCTATGCCTCCTTGGG
CTTTGGGGACAGTGGTGGTAGGGGTCCCTTATTCCCGGGAAGGGACTTGTTCAGGGATAATGAGGAGGCA
GGGTCCCAGGTAAGGGACTGGAATCCCAGCAGTTCTTGAGATGGCCCCAAGACCCATCTCTCTCTCTTAG
GGAAACCTTAATTAGAGACCTGTCATGGTAAGAGAGTTGTTTCTGTCAAACTCTGAGAAGAGTTTGAACC
CAAGGCTCCTTAGGTCTCAGTCCTTTCTAGATATTTAGCAATACCTCCCTAAACCCCAGTTCTTAGGCTA
ATCTTGGCTTGGGTACTAGGGTTGTGTAAGATCAGACACCTTCAAACAGATACAGGCCAATGTGATTTCT
GGGCCAAAGTTAGACTACCAAGGCCTGGACATGTGGTCAGAGGACTCTGTTGCATTCTTAAGAGCTGTGA
CTGGGGGTTAAGCAACAGTAAAGACCCCCAGTAGAGCCAACCCTGCTGTCCTCAGGTTCTCTGCGCACAG
AGTTTCATTTTAAGTGGCAGTAGGAAATGTGTACTGATAGTCAACCACTCGTATTTCTGTCACTGCAGCC
ATCCATCAATCCATCCATCATCCCCATCGTTCATCCTTGTAGCCAGCCATCCATTACCCTCCAGCCGCTC
ACTCATCATCTTTCCCGACTATCGTGATTCTCCAGCTTCTCTGCCCCCTCTCCCTGTGGGGATTCAGTCT
TTCACCTATTGACTCCTCCTTACTAGGATTCTCTGTCATGGGCCAGGCCTTGGATTCCATGGGTGGCTAT
GGTACTTTTCTGAGTCAGGTTTCCCAAGCTGGTCTGTTGCTCTTGCTATTCTCAGGGAACTGGACTTTCA
AGCTGGAGAGTATCCAGGGCATGCATGGGCCTTTACTCCACTCTTGCTCTGAGAGCAGAGGGAAGTTGCT
AGAAACCAGCAACTCCTCCCCCCCCCCCCCGAAGTTCTGAAGGCCTGTGAGACAGGAGCAGGGCCCCCAC
TGCCCTCTTGTGGACACCTGGGCTCCAAGTATACCTGGTTGTAGAACTTTGTGTTCTAGGGGTGCCCATG
GAGGAGGCCGAGGCCTGTGTGGGAGTGGTCTCCATGGCCTGCTCCTGCTTCTTCCCAGATTTGCCTCTTA
TCCTGCTTCTGGTTTGTGATACTTGGGCTCAGGATGGGAAGGGAGACTTAGGTTAGAAAGGGGGCACCTG
GAGGGGCCTATGCCCTTGTCCATTGTGTGTAGTTGTCAGTGTCGGGCCTGGAAATTCTCCCGGGGGCTTG
GAGGGGACTCCCCTTGCTTTCCAGAAGCTGGGTGTGGGCTGTGAACTTCATCTTCCTCCAGGGTTCAGGT
CTGTGTGAGTGTGCAAATGTGAGTGTCTGTGCATGTATGCCCATGTGCATGTATGCAGAACAGGGTGTAT
GCCCATGTGCATGTGTGAAGAGCAGGGTGCTGCTGAGGGTTGTCTGTGCCATGCTATATGTCTTTCTCAT
GAGTCAGTGGTCACCCTGAATGCATGTTTCCATTCAGGGATGGCCTACTGAGGGTGCGTGGCATCTTCTT
CCCAGTGCCCCTGTGTTCATCCCTTCATTCTCATACCATCATCTCTATTGTGACCCCCACACGGCACCAG
CCTTGATGGTGCTACCCTTTTGCTCCATCTATCCCTGTCTTGTTTGGGTTAGAAGCTGCGGTCTAATAAA
CAGCCACACCACCCACCACTCAGAGTACTTGTGCAGCAACCCACTGCCCTGGGGACTCTCCCATGAGCTT
TGCCTTCTTGGCTGAGTCTGCTCGCCTTGGATTTCATCCCCAGTTTATTCTTACTTCCCATTCACTCATT
GCACATTCACAGGGCAGGTGCACACACTCTCATGTTTCCACCAACATGAACACACATAGATATATGCATG
CTCATAGGTATGCACAGGCACACACTTGCTCACAGGGACATAGATATAGTGTGTCCACATATGTACTTAT
ACCCATATACATACCTATAAACCATAGGTGCACACAAACTCACTCCTCTCTTGCTGCACACAGGTACACA
CATGAAGGCACATGGACCCATCCATAAGCACTCACCAATACATAGACATGCATACACATATACTCTAGGC
ATGAAGGGTCTTCAAAGTCTCCGAGGCCTTACAAGCTTAGGTGGTGGTGTTTCTCCCTCCCTGGGCCCTG
ACCCCTCCCTGTGTTCTGTAGACCCTAAGGATGATGGACAGGCACTGGATGGAAGTGCAGGGATACTTTG
GATGAGCACAGAGTTTATTTCAGGAGTAGGGACAGGCAGGGTGGCTCAGTAGCAGATGCCATCTCCCTCT
GACATGATCACAGACACGCTGACATTGGTGGGTTTACCCGACAGACGGTCGATGGTCTTCTGGGTGAAGT
TCATGGGCAAGGCCTCGTGGCCCACCATGCAGGAGTACTGGTCACCCTGTTTCCAGAGTTCAGCTGATAC
ACGCAACACGCTTGTCACCAGGTAGGTGGTGGCTCCCTCGCCTGGCTCCTTTAGGGGCTCAAACACTAGG
TAGCTTTCTGGGGACAGCTCCTCATTTCCATGCAGCCATCGCACCAGCACTTCTTTAGGGTTGAAAGCTC
GCACCAGGCATGTCAGGGACACGAGCTCATTCAGGGCCAGCTCCTCCGACGGCGGCGGTAGCAGGTGGAC
CTGGGGTGGGAAGGTGTTCACTGGAAGGTAGAAAGAAGAGTTATGGCTCAGACAAGGAGAGCAAGACCCC
TCTGCCCTTCCCTTCTGGGCAGTTCCTCAGATAGCTCCAATTTCCCTCTGTGATATAAGGACAGGAGCAG
TTAGTTGAGCATCTGTATTATAGGAAGAAAGCAGGCATGTGAGCAGGGAACGTCATACAATGTCCCGGGT
ATGCATCTGGGCTCACCTGTGATTTTGGCAATTGTGCCAGTTAAGGTGTCAGACTCAGGATGGGTAACTG
TGCACTTGAATGATGCGCCACTGTTCCAGCGCTCAGCACAGCCAGGCAGGACGCTGGACACACTGTAGCA
GCCGCAGGAATTCTGCACAGCTTTCTTCTGCACTGCATCCTTCCCAGTGGAGGGCTCCCAGGTGAAGACA
GCTCCCTCAGGATTTCTCAGGCCATTCAGAGTACATGTGAGGCTGGCATCTGAACCCAGGAGCAGGTCCT
CAAGAGCTGGCCGCTGCAGTGACAGGCTGGGATGGCAGGAAGGAGGACAAGGAGGACAAGGAGGAGGAGG
ACCTGTAACAGAGAAGTCCTAGCAAATCAGTATATTCTCCTTTTCTCCTTTGCTGTCCCCTTTTCTGGAT
GTTCTGAGGCCTCAGTTCCTTATGGCCTGTTTACGCTTCCCTTCCCCCACCCCCATGGGAGGTTTCTGAG
GGTCCCTGTGAGGGTGTGCCTCAGAGGGATATATGGATCTAGATAAGGTAGAACTTATCCCACCCCCAGC
TGACCCCCTAACGTTCTTTACCAGAGCACTTCACATCCAATTCTTGGACGGCGTTAGAGTCATGTTGCAC
GGAACATTTCACGGATTCTCCTTCTGGGCACTCGACAGCTGGCAGGGTCAACTGGCTGCTCATGGTGTAC
CCTCCCCCAGAGGCCAGGGCAGGTGGGAAGTTTACGGTGGTTATATCCTTCCCACTCTTTCCCCAGGTCA
CATTCATCGTGCCGGAAGGGAAGTAATCGTGAATCAGGCAGCCGATTATCACTGGGTCACTTGACAGAGC
TCGTGGGAGTGTCAGTGGGTAGATGGTGGGATTTCTCGCAGAC
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): C. jejuni DNA vaccine pcDNA3.1(+)-cadF , C. jejuni DNA vaccine pcDNA3.1(+)-peblA , C. jejuni FspA1 protein vaccine , C. jejuni MBP-FlaA protein vaccine
2. 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): C. jejuni DNA vaccine pcDNA3.1(+)-cadF , C. jejuni DNA vaccine pcDNA3.1(+)-peblA , C. jejuni FspA1 protein vaccine , C. jejuni MBP-FlaA protein vaccine
IV. Vaccine Information
1. Avirulent Salmonella vaccine strain carrying C. jejuni cjaA gene
a. Vaccine Ontology ID:
VO_0004121
b. Type:
Recombinant vector vaccine
c. Antigen
Three C jejuni genes [cjaA ( cj0982c ) , cjaC ( cj0734c ) and cjaD ( cj0113 )] encoding highly immunogenic proteins which are conserved among different Campylobacter serotypes have been introduced into avirulent Salmonella enterica sv. Typhimurium (chi 4550 and chi 3987) strains of two different serotypes (UK-1 and SR) (Wyszynska et al., 2004). C. jejuni 72Dz/92 cjaA gene encodes a highly immunogenic protein which is conserved among different Campylobacter serotypes (Wyszynska et al., 2004). The surface antigen CjaA of Campylobacter jejuni is supported by the presence of an upstream gene with significant homology to ATP binding proteins (Martin et al., 1999).
d. Gene Engineering of cjaA
  • Type: Recombinant vector construction
  • Description: pUWA10A plasmid carrying CjaA was ligated into the pYA3341 plasmid and then transformed into E. coli χ6097 competent cells. It was later introduced by electroporation into two S. enterica sv. Typhimurium (χ3987 and χ4550) strains (Wyszynska et al., 2004).
  • Detailed Gene Information: Click here.
e. Adjuvant:
f. Preparation
Three gene libraries of Campylobacter jejuni 72Dz/92 DNA were prepared using lambda gt11, pSupercos and pWSK129 cloning vectors. Screening of the libraries revealed several immunoreactive clones (Pawelec et al., 1997).
g. Virulence
The vaccine vector is avirulent Salmonella enterica sv. Typhimurium (chi 4550 and chi 3987) strains of two different serotypes (UK-1 and SR) (Wyszynska et al., 2004).
h. Description
The constitutive expression of all analysed genes as measured by Western immunoblot technique was independent of the particular host strain. Specific rabbit anti-rCjaA antibody reacted not only with CjaA but also with other solute-binding proteins, components of the ABC transport system (CjaC protein), chosen as the protective antigen for animal experiments. Chickens orally immunized with Salmonella expressing Campylobacter cjaA gene developed serum IgG and mucosal IgA antibody responses against Campylobacter membrane proteins and Salmonella OMPs. Protection experiments show that chicken immunization with avirulent Salmonella carrying Campylobacter cjaA gene greatly reduces ability of heterologous wild type C. jejuni strain to colonize the bird cecum (Wyszynska et al., 2004).
i. Chicken Response
  • Host Strain: Commercial broiler chickens (Gallus gallus)
  • Vaccination Protocol: Commercial broiler chickens were obtained from the local hatchery on the day of hatch. Briefly, chickens deprived of food and water for 4 h were immunized orally with 100 μl of 109 CFU/ml of Salmonella χ3987 carrying pUWM251 (cjaA). Booster doses were administrated 2 weeks after primary immunization. Following vaccination, chickens were observed for the development of diarrhoea and other potential adverse side effects (Wyszynska et al., 2004).
  • Persistence: There was high anti-Campylobacter IgG titer present at the first time point (week 0), dropping at weeks 2 and 4. A moderate increase of Campylobacter specific IgG level was observed at week 6 followed by significant increase of anti-Campylobacter IgG level at week 8. Serum IgG titers to Campylobacter whole cell lysates followed a similar pattern, as those measured with membrane antigens, with respect to time, although the increase of anti-Campylobacter IgG titer at week 8 was not so significant. The results suggest that high IgG titer observed at the 0 week reflects maternally derived immunity while increasing serum IgG titers at 6 and 8 weeks is a consequence of vaccination (Wyszynska et al., 2004).
  • Immune Response: Mucosal anti-Salmonella and anti-Campylobacter IgA antibodies were present in samples taken from chickens inoculated with Salmonella/pUWM251 at every tested time point. In contrast to serum IgG, the kinetics of IgA responses to both antigens were similar. In intestinal secretions the level of the antibodies dropped at week 2 and then peaked 2 weeks after the booster. During the next 2 weeks, IgA titers decreased and maintained at almost the same level during the remainder of the experiment. Since IgA antibodies directed towards both antigens were present in the intestinal fluids of 1-day-old birds, similarly to IgG antibodies, IgA present at 0 week were maternally derived. In intestinal secretions, taken from different parts of chicken gut (rectum and jejunum), levels of IgA antibodies to Campylobacter and Salmonella antigens also peaked 2 weeks after the secondary immunization. Intestinal IgA titers to Campylobacter whole cell lysates followed the similar patterns as those measured with membrane antigens (Wyszynska et al., 2004).
  • Side Effects: No adverse side effects were observed (Wyszynska et al., 2004).
  • Challenge Protocol: Two weeks after booster, all chicks received a dose containing approximately 2×10^9 CFU/ml of the wild type C. jejuni/pUOA18 strain in 0.1 ml PBS with gelatine. Campylobacter colonization was confirmed on days 3, 6, 9 and 12 after the challenge. In each instance, four chicks were euthanized, the intestine was excised and the C. jejuni present in chicken cecal contents were enumerated by plating (Wyszynska et al., 2004).
  • Efficacy: Protection experiment showed that chicken immunization with avirulent Salmonella carrying Campylobacter cjaA gene greatly reduced the ability of heterologous wild type C jejuni strain to colonize the bird cecum (Wyszynska et al., 2004).
  • Description: It is well documented that poultry and poultry products are the major source of human campylobacteriosis and salmonellosis. The avirulent Salmonella vaccine strains expressing Campylobacter antigen can be potentially used as a bivalent chicken vaccine (Wyszynska et al., 2004).
2. C. jejuni DNA vaccine pcDNA3.1(+)-cadF
a. Vaccine Ontology ID:
VO_0011545
b. Type:
DNA vaccine
c. Status:
Research
d. Antigen
C. jejuni fibronectin binding protein cadF
e. Gene Engineering of cadF
  • Type: DNA vaccine construction
  • Description: The chitosan-DNA vaccines was prepared by embedding pcDNA3.1(+)-cadF with chitosan (Zheng et al., 2007).
  • Detailed Gene Information: Click here.
f. Vector:
pcDNA3.1(+) (Zheng et al., 2007)
g. Immunization Route
Intranasal
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: BALB/c mice were intranasally immunized in a four-dose primary series (7 d intervals) at doses of 60 microg chitosan-DNA vaccines each time (Zheng et al., 2007).
  • Challenge Protocol: Mice were attacked repeatedly through intragastric administration of C. jejuni HS:19 at the 8th week after the immunization and protective efficacy was determined by detecting the degrees of protection afforded against C. jejuni invaded (Zheng et al., 2007).
  • Efficacy: The mice immunized with chitosan-DNA vaccines have generated high levels of IgA and IgG from the sera and IgA from the intestinal secretions and the P/N value went up to 20.58, 30.13 and 6.87 respectively. Moreover the chitosan-DNA vaccines induced strongest level of protection in BALB/c mice against challenge with C. jejuni HS:19 strain and the protective efficacies was 93.70. The results of this study indicate that the chitosan-DNA vaccines could induce significant protective immunity against C. jejuni challenge in the mice model (Zheng et al., 2007).
3. C. jejuni DNA vaccine pcDNA3.1(+)-peblA
a. Vaccine Ontology ID:
VO_0011488
b. Type:
DNA vaccine
c. Status:
Research
d. Antigen
C. jejuni bifunctional adhesin/ABC transporter aspartate/glutamate-binding protein
e. Gene Engineering of peb1A
  • Type: DNA vaccine construction
  • Description: The chitosan-DNA vaccine was prepared by embedding pcDNA3.1(+)-peblA with chitosan (Zheng et al., 2007).
  • Detailed Gene Information: Click here.
f. Vector:
pcDNA3.1(+) (Zheng et al., 2007)
g. Immunization Route
Intranasal
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: BALB/c mice were intranasally immunized in a four-dose primary series (7 d intervals) at doses of 60 microg chitosan-DNA vaccines each time (Zheng et al., 2007).
  • Immune Response: The mice immunized with chitosan-DNA vaccines have generated high levels of IgA and IgG from the sera and IgA from the intestinal secretions and the P/N value went up to 20.58, 30.13 and 6.87, respectively (Zheng et al., 2007).
  • Challenge Protocol: Mice were attacked repeatedly through intragastric administration of C. jejuni HS:19 at the 8th week after the immunization and protective efficacy was determined by detecting the degrees of protection afforded against C. jejuni invaded (Zheng et al., 2007).
  • Efficacy: The chitosan-DNA vaccines induced strongest level of protection in BALB/c mice against challenge with C. jejuni HS:19 strain and the protective efficacies was 93.70 (Zheng et al., 2007).
4. C. jejuni FlaC protein vaccine
a. Vaccine Ontology ID:
VO_0011495
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
C. jejuni flagellin subunit protein FlaC
e. Gene Engineering of FlaC
  • Type: Recombinant protein preparation
  • Description: The flaC gene from C. jejuni 81-176 was expressed in Escherichia coli as hexahistidine-tagged proteins in pET-19b. Strains of BL21(DE3) containing each clone were grown in Luria broth containing 100 μg/ml ampicillin and proteins were purified by nickel chromatography under native conditions (Baqar et al., 2008).
  • Detailed Gene Information: Click here.
f. Adjuvant:
g. Immunization Route
Intranasal
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were lightly anesthetized with isoflurane, and 30 μl of phosphate-buffered saline (PBS) alone or PBS containing 5 μg (7 to 10 mice per group) or 25 or 100 μg (10 to 18 mice per group) of protein was applied a drop (5 to 6 μl) at a time to the external nares. A total of three vaccinations for each dose level of each protein were delivered at 2-week intervals. To determine efficacy, animals receiving 100 μg of each protein alone or with 1 μg of LTR192G as the adjuvant were challenged with homologous or heterologous strains of C. jejuni. Following vaccination, animals were observed for two consecutive days for the development of vaccine-associated side effects (Baqar et al., 2008).
  • Challenge Protocol: Twenty-eight days following the last vaccination, mice were intranasally challenged with 3 × 10^9 CFU of C. jejuni 81-176 or CG8486 (Baqar et al., 2008).
  • Efficacy: FlaC provided an 18% protection against disease from C. jejuni 81-176 (Baqar et al., 2008).
5. C. jejuni FspA1 protein vaccine
a. Vaccine Ontology ID:
VO_0011485
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
C. jejuni flagellum-secreted protein FspA1
e. Gene Engineering of fspA1
  • Type: Recombinant protein preparation
  • Description: The fspA1 gene from C. jejuni 81-176 was expressed in Escherichia coli as hexahistidine-tagged proteins in pET-19b. Strains of BL21(DE3) containing each clone were grown in Luria broth containing 100 μg/ml ampicillin and proteins were purified by nickel chromatography under native conditions (Baqar et al., 2008).
  • Detailed Gene Information: Click here.
f. Adjuvant:
g. Immunization Route
Intranasal
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were lightly anesthetized with isoflurane, and 30 μl of phosphate-buffered saline (PBS) alone or PBS containing 5 μg (7 to 10 mice per group) or 25 or 100 μg (10 to 18 mice per group) of protein was applied a drop (5 to 6 μl) at a time to the external nares. A total of three vaccinations for each dose level of each protein were delivered at 2-week intervals. To determine efficacy, animals receiving 100 μg of each protein alone or with 1 μg of LTR192G as the adjuvant were challenged with homologous or heterologous strains of C. jejuni. Following vaccination, animals were observed for two consecutive days for the development of vaccine-associated side effects (Baqar et al., 2008).
  • Challenge Protocol: Twenty-eight days following the last vaccination, mice were intranasally challenged with 3 × 10^9 CFU of C. jejuni 81-176 or CG8486 (Baqar et al., 2008).
  • Efficacy: Immunization with FspA1 resulted in 57.8% protection without adjuvant or 63.8% protection with adjuvant against homologous challenge with 81-176 (Baqar et al., 2008).
  • Host Gene Response of IgA
    • Gene Response: FspA1 induced significantly high levels of fecal IgA in mice 7 days after last vaccination. These results are compared to PBS vaccinated mice (Baqar et al., 2008).
    • Detailed Gene Information: Click here.
  • Host Gene Response of IgG
    • Gene Response: FspA1 induced significantly high levels of serum immunoglobulin G (IgG) in mice 18-20 days after 3rd vaccination. These results are compared to PBS vaccinated mice (Baqar et al., 2008).
    • Detailed Gene Information: Click here.
6. C. jejuni FspA2 protein vaccine
a. Vaccine Ontology ID:
VO_0011487
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
C. jejuni flagellum-secreted protein FspA2
e. Gene Engineering of fspA2
  • Type: Recombinant protein preparation
  • Description: The fspA2 gene from C. jejuni CG8486 were expressed in Escherichia coli as hexahistidine-tagged proteins in pET-19b. Strains of BL21(DE3) containing each clone were grown in Luria broth containing 100 μg/ml ampicillin and proteins were purified by nickel chromatography under native conditions (Baqar et al., 2008).
  • Detailed Gene Information: Click here.
f. Adjuvant:
g. Immunization Route
Intranasal
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were lightly anesthetized with isoflurane, and 30 μl of phosphate-buffered saline (PBS) alone or PBS containing 5 μg (7 to 10 mice per group) or 25 or 100 μg (10 to 18 mice per group) of protein was applied a drop (5 to 6 μl) at a time to the external nares. A total of three vaccinations for each dose level of each protein were delivered at 2-week intervals. To determine efficacy, animals receiving 100 μg of each protein alone or with 1 μg of LTR192G as the adjuvant were challenged with homologous or heterologous strains of C. jejuni. Following vaccination, animals were observed for two consecutive days for the development of vaccine-associated side effects (Baqar et al., 2008).
  • Challenge Protocol: Twenty-eight days following the last vaccination, mice were intranasally challenged with 3 × 10^9 CFU of C. jejuni 81-176 or CG8486 (Baqar et al., 2008).
  • Efficacy: Immunization with FspA2 provided 38.4% (without adjuvant) or 47.2% (with adjuvant) protection against disease from homologous challenge with CG8486 (Baqar et al., 2008).
7. C. jejuni MBP-FlaA protein vaccine
a. Vaccine Ontology ID:
VO_0011493
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
C. jejuni structural flagella protein flaA and maltose-binding protein MBP
e. Gene Engineering of FlaA from C. jejuni 81-176
  • Type: Recombinant protein preparation
  • Description: Purification schemes were essentially as recommended by NEB. DH5α containing the flagellin-MBP fusion was grown overnight in 10 ml of rich medium (10 g of tryptone, 5 g of yeast extract, 5 g of NaCl, and 2 g of glucose/liter) supplemented with 100 μg of ampicillin per ml and used to inoculate a fresh 1-liter culture of the same medium. This culture was grown with shaking at 37°C to an optical density at 600 nm of 0.5, and IPTG (isopropyl-β-d-thiogalactoside; Gibco, Gaithersburg, Md.) was added to a final concentration of 0.3 mM (Lee et al., 1999).
  • Detailed Gene Information: Click here.
f. Adjuvant:
g. Immunization Route
Intranasal
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were anesthetized with methoxyflurane (Metofane; Pitman-Moore, Mundelein, Ill.) and immunized intranasally with 30 to 35 μl of fusion protein by using a micropipette. The doses used were 0, 3, 6, 12, 25, or 50 μg of fusion protein in phosphate-buffered saline (PBS), either alone or in combination with 5 μg of the genetically modified heat-labile enterotoxin of E. coli, designated LTR192G as an adjuvant. A second dose was administered 8 days after the first vaccination (Lee et al., 1999).
  • Challenge Protocol: Mice were intranasally challenged with 2 × 10^9 C. jejuni bacteria/mouse 26 days after the second vaccination, and the animals were monitored for sickness and death for 5 days (Lee et al., 1999).
  • Efficacy: The protective efficacies of a 50 microgram of MBP-FlaA plus LT(R192G) dose against disease symptoms and intestinal colonization were 81.1 and 84%, respectively. When mice which had been immunized with 50 microgram of MBP-FlaA plus LT(R192G) intranasally were challenged orally with 8 x 10^10, 8 x 10^9, or 8 x 10^8 cells of strain 81-176, the protective efficacies against intestinal colonization at 7 days postinfection were 71.4, 71.4, and 100%, respectively (Lee et al., 1999).
  • Host Gene Response of IgA
    • Gene Response: Stimulation of FlaA-specific intestinal secretory IgA (sIgA) responses required immunization with higher doses of MBP-FlaA (>/=25 microgram) or coadministration of lower doses with the adjuvant. IgA titers were significant 7 days after immunization as compared to PBS-vaccinated mice (Lee et al., 1999).
    • Detailed Gene Information: Click here.
  • Host Gene Response of IgG
    • Gene Response: The full range of MBP-FlaA doses were effective in eliciting significant antigen-specific serum immunoglobulin G (IgG) responses, and these responses were enhanced by adjuvant use, except in the highest dosing group. The results were compared to PBS vaccinated mice 7 days after immunization (Lee et al., 1999).
    • Detailed Gene Information: Click here.
8. C. jejuni PorA protein vaccine
a. Vaccine Ontology ID:
VO_0004203
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Recombinant PorA protein
e. Gene Engineering of PorA
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant:
g. Immunization Route
orally
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: BALB/c mice were orally vaccinated twice at a weekly interval with the purified GST-PorA fusion protein combined with a modified heat-labile enterotoxin of Escherichia coli toxin, LT R192G, as an adjuvant. Mice immunized with LT R192G or PBS (pH 7.2) alone were included as controls. Vaccination was done by using a stainless steel, curved-ball-tip feeding needle (20 gauge, 1.5-in. long; Popper and Sons, Inc., New Hyde Park, NY). Just prior to vaccination, gastric acidity was neutralized with two doses (0.5 ml each) of a 5% sodium bicarbonate (pH 8.5) solution given as an oral gavage at an interval of 15 min. An amount of 300 µg of the GST-PorA fusion protein mixed with 5 µg of LT R192G in a total volume of 300 µl in PBS (pH 7.2) was given to each of nine animals. Another group of mice was each fed with 5 µg of LT R192G and yet another group each fed with 1x PBS (pH 7.2) (Abimiku et al., 1989; Islam et al., 2010)
  • Challenge Protocol: Mice were challenged with bacterial culture 3 weeks after the second vaccine dose, immediately after tail vein blood collection. A 48-h bacterial culture grown on campylobacter agar was suspended in PBS (pH 7.2) to a concentration of 2 x 109 CFU per ml, and 0.5 ml of the suspension was orally fed to the mice immediately after neutralization of the gastric acidity (Islam et al., 2010).
  • Efficacy: The vaccine produced robust antibody responses against both antigens in serum and secretion. Since strain C31 was a poor colonizer, homologous protection could not be studied. The protective efficacies of heterologous strains were 43% (for strain 48, P < 0.001), 29% (for strain 75, P < 0.005), and 42% (for strain 111, P < 0.001) for the 9-day period compared to control mice given phosphate-buffered saline (Islam et al., 2010).
9. deltaphoP/Q S. typhimurium strains expressing PEB1-ss
a. Vaccine Ontology ID:
VO_0004124
b. Type:
Recombinant vector vaccine
c. Antigen
Campylobacter PEB1 is an adherence factor that is highly immunogenic in humans (Sizemore et al., 2006).
d. Preparation
Three live, attenuated deltaphoP/Q Salmonella enteric serovar Typhimurium strains expressing PEB1 minus its signal sequence (PEB1-ss) from three different plasmids were prepared. The three plasmids include a pBR-based asd plasmid, an arabinose-based runaway plasmid, which each expressed PEB1-ss in the bacterial cytosol, and a PEB1::HlyA fusion plasmid that directs secretion of PEB1-ss into the extracellular milieu (Sizemore et al., 2006).
e. Virulence
PEB1 is an adherence factor that is highly immunogenic in humans (Sizemore et al., 2006).
f. Description
PEB1, the major cell-binding factor of Campylobacter jejuni, is a homolog of the binding component in Gram-negative nutrient transport systems (Prokhorova et al., 2006).
g. Mouse Response
  • Host Strain: Female, BALB/c Mouse Specific Pathogen Free (MSP) 7–9 weeks of age from Taconic
  • Vaccination Protocol: Mice that had been acclimated for 5 days were vaccinated with freshly prepared inocula on days 1 and 12 of the experiment by pipet feeding. The target concentration for this experiment was 1–2.5E8 in 50 μl (Sizemore et al., 2006).
  • Persistence: MGN4735 was able to colonize the intestine to a high level over the entire test period of 9 days post-inoculation while those mice that survived challenge with 81-176 cleared the infection (Sizemore et al., 2006).
  • Immune Response: Serum IgG responses specific for PEB1-ss were induced by pBR-derived and runaway plasmids, with 100 and 90% seroconversion, respectively, at a 1:500 dilution of anti-sera as measured by Western blot analysis, while the PEB1-ss::HlyA fusion plasmid induced serum IgG in only 20% of the mice (Sizemore et al., 2006).
  • Side Effects: no adverse side effects were observed
  • Challenge Protocol: Challenge of vaccinated BALB/c mice was based on the model developed by Baqar et al. (Baqar et al., 1995b). C. jejuni strain 81-176 served as the challenge strain in the oral model (Sizemore et al., 2006).
  • Efficacy: Although significant levels of anti-PEB serum IgG were induced, no protection against oral Campylobacter jejuni challenge was observed (Sizemore et al., 2006).
  • Description: Three live attenuated ΔphoP/Q Salmonella enteric serovar Typhimurium strains expressing PEB1 minus its signal sequence (PEB1-ss) from three different plasmids: a pBR-based asd plasmid, an arabinose-based runaway plasmid, which each expressed PEB1-ss in the bacterial cytosol, and a PEB1::HlyA fusion plasmid that directs secretion of PEB1-ss into the extracellular milieu are described above (Sizemore et al., 2006).
10. Inactivated C. jejuni whole-cell (CWC)
a. Vaccine Ontology ID:
VO_0004100
b. Type:
Inactivated or "killed" vaccine
c. Antigen
inactivated whole-cell Campylobacter jejuni (CWC)
d. Adjuvant:
  • VO ID: VO_0001322
  • Description: 25 mg of a mucosal adjuvant, the heat-labile enterotoxin of Escherichia coli (LT) has been used (Baqar et al., 1995b).
e. Preparation
The CWC vaccine is prepared from the 81-176 strain of C. jejuni and consists of a 1:1 mixture of heat (60 C, 60 min)- and formalin (0.02 M)-inactivated Campylobacter whole cells. Each vaccination group receives oral doses of CWC vaccine containing bacterial cells alone or in combination with 25 mg of LT. Just prior to vaccination, gastric acidity is neutralized by 2 doses of a 5% NaHCO3 solution (pH 8.5) with a 15-min interval (Baqar et al., 1995b).
f. Virulence
Volunteers given the CWC vaccine have similar IgA-ASC and sIgA responses and in vitro induction of IFN to Campylobacter antigens (Walker, 2005).
g. Description
Whole-cell vaccine formulations deserve further evaluation as candidate vaccines and the potential value of mucosal adjuvants, like LT, in enteric vaccine development are not in doubt (Baqar et al., 1995).
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were orally immunized in a three-dose primary series with CWC vaccine particles alone or in combination with a mucosal adjuvant, the heat-labile enterotoxin of Escherichia coli (LT) (Baqar et al., 1995b).
  • Persistence: Ninety percent of control animals remain colonized for 9 days post-challenge. A similar colonization pattern is observed in mice vaccinated with LT alone. Clearance of challenge organisms from mice receiving CWC vaccine alone appear to be dependent on the amount of vaccine administered. Although 80% of the mice receiving the highest vaccine dose cleared the infection within 3 days of challenge, the remaining 20% were colonized for the remainder of the study period (Baqar et al., 1995b).
  • Immune Response: Campylobacter-specific intestinal IgA responses are dependent on the use of LT, whereas IgA and IgG responses in serum are not. Intestinal lavage fluid collected from sham-immunized animals at 7 d post-vaccination have no detectable levels of Campylobacter- or LT-specific secretory IgA (sIgA) or IgG. When CWC is administered over a 10,000-fold range of doses, only 20% of the mice immunized with the low or intermediate doses mount a significant Campylobacter-specific sIgA response. In contrast, administering the same doses with LT resulted in a substantial enhancement of the sIgA response to vaccine-associated Campylobacter antigens in all vaccination groups (Baqar et al., 1995b).
  • Side Effects: Both the CWC and CWC-LT vaccine formulations are well tolerated, with no weight loss or signs consistent with toxicity in immunized animals. Histopathological examination of the intestinal mucosa and other organ systems following vaccination fails to detect evidence of tissue damage or severe inflammation (Baqar et al., 1995b).
  • Challenge Protocol: At ~4 wks post-vaccination, mice were challenged orally with C. jejuni, and duration of colonization was determined by the monitoring of fecal shedding. Efficacy was determined by measuring the degree of protection afforded against intestinal colonization and systemic dissemination of challenge organisms (Baqar et al., 1995b).
  • Efficacy: Colonization resistance was induced over a broad range of vaccine doses when LT was included. However, only the highest dose of CWC alone gave comparable levels of protection. Both formulations provided equivalent protection against systemic spread of challenge organisms. These results indicate that both whole-cell vaccine formulations deserve further evaluation as candidate vaccines and also highlight the potential value of mucosal adjuvants, like LT, in enteric vaccine development (Baqar et al., 1995b).
  • Description: Inactivated Campylobacter whole-cell vaccines (CWC) must be given orally in large doses to be effective. Drawbacks could be overcome by the coadministration of LT (Baqar et al., 1995b).
i. Ferret Response
  • Host Strain: Mustela putorius furo
  • Vaccination Protocol: Food was withheld prior to challenge. The vaccine dose was administered orally via a pediatric nasogastric tube. After 60 min, animals were administered paragoric i.p. to slow peristalsis. Drinking water was supplemented with tetracycline for three days prior to rechallenge to decrease the competing intestinal microflora (Burr et al., 2005).
  • Persistence: An oral regimen delivered on days 0, 3, 5, and 7 provided enhanced protection following oral homologous challenge delivered at Days 0 and 14. The percent protection observed was 100% in previously infected ferrets, 50% in a two-dose CWC group, and 89% in a four-dose CWC group. Protection was afforded through vaccination with sufficient inactivated whole cell vaccine, but protection was obtained regardless of the inclusion of the adjuvant LTR192G (Burr et al., 2005).
  • Immune Response: Antibodies generated during natural infection in ferrets by either strain 81-176 or strain VC167 appeared to react more strongly to glycosylated flagellins isolated from Campylobacter spp . than to unglycosylated , recombinant flagellins isolated from E coli . (Lee et al., 1999)
  • Side Effects: Following infection, animals were monitored three times daily for signs of diarrhea, dehydration, appetite and water consumption. Rectal swabs from each ferret were cultured for C. jejuni by direct plating on C. jejuni selective agar. At the appropriate time, blood samples were obtained by bleeding the animals from the jugular vein while under light anesthesia using acepromazine-ketamine. Collected sera were assayed for specific anti-Campylobacter immunoglobulin levels. At the conclusion of each experiment, animals were lightly anaesthetized with acepromazine-ketamine then euthanized by intracardiac injection of sodium pentobarbital (Burr et al., 2005).
  • Challenge Protocol: Food was withheld prior to challenge. Animals received ketamine plus acepromazine i.m. Following sedation, the vaccine or challenge dose was administered orally. Animals being fed live organisms were administered paragoric i.p. For secondary challenge the procedure was otherwise identical, except that NaHCO3 was delivered prior to challenge. In addition, drinking water was supplemented with tetracycline prior to rechallenge. All challenge doses were monitored by plate counts (Burr et al., 2005).
  • Efficacy: Ferrets show some conservation of protection against disease induced by Campylobacter. Upon rechallenge, homologous protection was 67-84%. Heterologous challenge resulted in 67-80% protection. These data indicate that the strain chosen for use in humans protects against disease caused by two of the major serotypes responsible for human disease (Burr et al., 2005).
  • Description: The strong IgG responses seen upon rechallenge of vaccinated or previously challenged animals may not be protective in themselves but could indicate the magnitude of other unmeasured antibody responses following immunization. Whatever the exact nature of the protective immune responses associated with the CWC vaccine, it is clear that the vaccine offers protection which may be relatively conserved among clinically important serotypes of Campylobacter (Burr et al., 2005).
j. Chicken Response
  • Vaccination Protocol: A hybrid protein was administered as a vaccine to chickens either orally or i.m. Alimentary secretions were collected , and specific antibodies were assayed by western blot analyses (Khoury et al., 1995).
  • Persistence: Seventy-two percent of the birds vaccinated orally with 1000 micrograms protein showed detectable antibodies against C jejuni flagellin in the excreta . None of the control birds produced detectable antibody to this antigen (Khoury et al., 1995).
  • Immune Response: Chickens orally immunized developed serum IgG and mucosal IgA responses against Campylobacter membrane proteins, as measured by an ELISA test. Protection experiments show that chicken immunization greatly reduces the ability of heterologous wild type C jejuni strain to colonize the bird cecum (Wyszynska et al., 2004).
  • Side Effects: No adverse side effects have been associated with this vaccine in chickens.
  • Challenge Protocol: For trials to demonstrate clearance of Campylobacter, groups of chickens were vaccinated with the hybrid protein at 2 and 4 wk of age and challenged at 3 wk with an excess of Cjejuni. The number of birds that remained colonized at 5 wk of age was significantly lower among the vaccinated birds than among controls (Khoury et al., 1995).
  • Efficacy: The nature of the antibody response to MOMP during in vivo infection is not well understood. Antibody responses elicited in Campylobacter-colonized chickens demonstrates that proteoliposomes restore reactivity to rabbit antibodies. Sera from naturally or experimentally infected chickens reacts weakly, suggesting that the chicken antibody response is predominantly directed against conformational epitopes. These observations provide direct evidence for conformation-dependent humoral responses induced by Campylobacter infection, demonstrate that C jejuni is immunogenic in its natural host and suggest that proteoliposomes may be potentially used for the evaluation of vaccines (Huang et al., 2007).
  • Description: This is a conserved immunodominant protein in this organism and a promising vaccine candidate because the protein is expressed in multiple Campylobacter isolates from both chicken and human hosts (Martin et al., 1999).
11. MBP fused on Campylobacter FlaA (MBP-FlaA)
a. Vaccine Ontology ID:
VO_0004101
b. Type:
Conjugate vaccine
c. Antigen
recombinant protein comprising the maltose-binding protein (MBP) of E. coli fused to amino acids 5 to 337 of the FlaA flagellin of Campylobacter coli VC167 (Lee et al., 1999)
d. Gene Engineering of FlaA from C. jejuni NCTC 11168
  • Type: flagellin protein
  • Description:
  • Detailed Gene Information: Click here.
e. Adjuvant:
  • VO ID: VO_0001321
  • Description: immunization occurs with the mutant E. coli heat-labile enterotoxin (LT( R192G)) as a mucosal adjuvant (Lee et al., 1999)
f. Preparation
Part of the flaA gene ( 780 base pairs ) was cloned in plasmid pBEB downstream and in frame with the LT-B to allow expression of a hybrid protein . Transformed E coli chi 6097 expressed the hybrid protein ( 43 kdaltons ) in inclusion bodies at mid log phase . The inclusion bodies were isolated , and the identity of the protein was verified by western blot . (Khoury et al., 1995)
g. Virulence
The full range of MBP-FlaA doses were effective in eliciting antigen-specific serum IgG responses, and these responses were enhanced by adjuvant use. Stimulation of FlaA-specific intestinal secretory IgA (sIgA) responses required immunization with higher doses of MBP-FlaA or coadministration of lower doses with the adjuvant (Lee et al., 1999).
h. Description
A mucosal vaccine was used in an effort to elicit serum IgG and intestinal secretory IgA. A genetic hybrid of the Campylobacter jejuni flaA gene with LT-B of Escherichia coli and assessment of the efficacy of the hybrid protein has been developed an oral chicken vaccine (Wilkinson et al., 2003).
i. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were immunized intranasally with two doses of 3 to 50 mg of MBP-FlaA, given 8 days apart, with or without 5 mg of the mutant E. coli heat-labile enterotoxin (LTR192G) as a mucosal adjuvant (Lee et al., 1999).
  • Persistence: The results showed that, when challenged with bacteria, there was a reduction in colonization as early as 3 days after infection and that no campylobacter organisms could be detected in stools by 7 days post-feeding (Lee et al., 1999).
  • Immune Response: Stimulation of FlaA-specific intestinal secretory IgA (sIgA) responses required immunization with higher doses of MBP-FlaA or co-administration of lower doses with the adjuvant (Lee et al., 1999).
  • Side Effects: Animals were monitored for sickness and death for 5 days and only minimal adverse side effects were encountered (Lee et al., 1999).
  • Challenge Protocol: Mice were intranasally challenged after the second vaccination. Fecal excretion of C. jejuni was monitored daily for 10-14 days after challenge by culturing fecal homogenates. Putative colonies were confirmed by morphology and oxidase reactions. Mice were challenged orally with 0.5 ml of various doses of C. jejuni. Fecal excretion was monitored as described above for 7-9 days (Lee et al., 1999).
  • Efficacy: The full range of MBP-FlaA doses were effective in eliciting antigen-specific serum IgG responses, and these responses were enhanced by adjuvant use, except in the highest dosing group. When vaccinated mice were challenged intranasally 26 days after immunization, the best protection was seen in animals given 50 mg of MBP-FlaA plus LTR192G. The protective efficacies of this dose against disease symptoms and intestinal colonization were 81.1 and 84%, respectively. When mice which had been immunized intranasally were challenged orally with 8 x 10^10, 8 x 10^9, or 8 x 10^8 cells of strain 81-176, the protective efficacies against intestinal colonization at 7 days postinfection were 71.4, 71.4, and 100%, respectively (Lee et al., 1999).
  • Description: It is interesting that antibodies generated during natural infection by either strain 81-176 or strain VC167 appear to react more strongly to glycosylated flagellins isolated from Campylobacter spp. than to unglycosylated, recombinant flagellins isolated from E. coli. Immunization with the recombinant fusion protein lacking post-translational modifications may lead to antibody production against epitopes which are less immunogenic in the native molecule due to differences in folding and/or masking by the carbohydrate moiety but are, nonetheless, capable of eliciting a protective immune response. Further evaluation of this recombinant flagellin is ongoing as a vaccine in a ferret diarrheal disease model (Lee et al., 1999).
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