VIOLIN: Vaccine Investigation and Online Information Network

Coxiella burnetii

Table of Contents

General Information
Vaccine Related Pathogen Genes
1. ankyrin repeat domain protein (Protective antigen)
2. com1 (Protective antigen)
3. enhA1 (Protective antigen)
4. htpB (Protective antigen)
5. icmO (Protective antigen)
6. mip (Protective antigen)
7. OmpA (Protective antigen)
8. p1 (Protective antigen)
9. ybgF (Protective antigen)
Vaccine Related Host Genes
1. IgM (partial)
Vaccine Information
References

I. General Information

1. NCBI Taxonomy ID:

777

2. Disease:

Q fever

3. Introduction

Coxiella burnetii is an intracellular organism that causes Q fever. Unlike other rickettisiae, however, C. burnetii, multiplies in the phagolysosomal vacuoles and remains in the vacuoles throughout its life cycle (Burton et al., 1971; Burton et al., 1978; Ormsbee, 1969). The microorganism is able to survive under the hostile conditions within the phagolysosomes (Akporiaye and Baca, 1983). C. burnetii also has two phases (phase I and phase II) based on the pathways involved and the cell coating (Mege et al., 1997; Capo et al., 1999). Phase I organisms are more virulent and have complete smooth-type lipopolysaccharide (LPS) while phase II organisms are avirulent and have incomplete rough-type LPS (Hackstadt et al., 1985) . Due to highly resistance to chemical agents and hostile environments, and the low number of C. burnetii required for an infection through inhalation, Coxiella burnetii is listed CDC category B priority agent. Common symptoms for Q fever include fever, headache, malaise, and myalgia.

4. Microbial Pathogenesis

C. burnetii is found in large numbers in birth fluids of goat and cows (Stoker and Marmion, 1955). Humans are then infected by inhaling from the infected aerosols or dust particles with the contaminated birth fluids. Approximately only 10 microorganisms are needed to infect humans (Tigertt et al., 1961). Based on animal models, C. burnetii is first engulfed by macrophages after inital infection in the lungs (Burton et al., 1971; Burton et al., 1978). The microorganism grows within the acidic environment, with a pH around 4.7 - 4.8 (Ohkuma and Poole, 1978), in the phagolysosome and eventually rupture the host cells and infect other neighboring cells (Hackstadt and Williams, 1981; Burton et al., 1971). C. burnetii suppresses the host immune responses and avoids host cell activation (avoid recognition by TLR). As a result, the microogranism is able to persist within phagolysosome (Zamboni et al., 2004; Shannon et al., 2005).

Link to pathogenesis of Coxiella burnetii in HazARD.

5. Host Ranges and Animal Models

Several species are infected by C. burnetii. However, the disease seems to be more severe in human beings (Waag, 2007). C. burnetii has also been found to cause abortions in humans, goats, sheeps, and cattles (Langley et al., 2003; Palmer et al., 1983; Waldhalm et al., 1978). C. burnetii can be cultured and isolated using chicken embryo yolk sacs. Model organisms normally use for infection research include mice and guinea pigs, and sheeps (Williams and Thompson, 1991).

6. Host Protective Immunity

Antibodies produced by the immune system is not the primary mechanism used for resistance. Studies have shown that the activation of monocytes and macrophages by gamma interferon results in the production of active nitrogen and oxygen intermediates. This mechanism results in the killing of C. burnetii (Brennan et al., 2004; Turco et al., 1984). However, C. burnetii minimizes detection by the host cell, thereby minimizes the killing by the intermediates (see Microbial Pathogensis for more information).

II. Vaccine Related Pathogen Genes

1. ankyrin repeat domain protein

Gene Name : ankyrin repeat domain protein
Sequence Strain (Species/Organism) : Coxiella burnetii Q321]
NCBI Protein GI : EDR36478
Taxonomy ID : 360117
Protein Name : ankyrin repeat domain protein
Protein pI : 8.44
Protein Weight : 73674.68
Protein Length : 748
Protein Note : identified by match to protein family HMM PF00023

Protein Sequence : Show Sequence

>EDR36478.1 ankyrin repeat domain protein [Coxiella burnetii Q321]
MGHQSLNPLESRYRQLKDAMRRRSWSDVIECLWECDDAVAFQSDNQGNTVLHEAVLLEDSKILTQLLTWL
VRKNLLLTALEQTNQKKETVWHLVCQSKNPKALLMPTIQTCYQIWKGDKRDYVREFGERKKSIAEATKET
KKRKAEQKDSDQAAEQKSTKKERPISEFPPPYPDFKINKPNSFNKTPFDLLLEKAENLDAIELLLQYPWL
GIEIKENASKVIDVRKTLHRAQSSTFFRAQPARLAADEKAPESSSTWTVETSHRLLNVFFWYATHCGAQK
EAELLWEKGADFSSVNESGWNAILWAASSGDIKTLKWCLDPERWKGTWVEKRGGPYAITTNDGSNVLLLA
IFSGNLKMLEDLEKAGLSLDNLSTARKHPVSAAIRSGNPKMVAKLLKSFSLEEVVNYHTDDPFLVAAEQG
YPLLLENLKKKMKKKNFPPSSLKPLLLINSPAANIAAFKNHLDVLSWLKKIQLESFSFFPDKRSQLATLI
SAVIANQVGIVEWLIEDKFQADWQSTKDDYGNDLVLLTTGADHLEMLKWLVERKGLPLNSRNKQGRGAVL
MAARYGCFEILKWLIEEKKLSLNDMDSAKSNVVLAGARSGNLALLKWLIDEKNLSLSTTDAAGNTPCLMA
SQSGNVDMMEWLINEKNNLYLFKNQQFPLETTTLLKIMES

Molecule Role : Protective antigen
Molecule Role Annotation : (Wang et al., 2013)

2. com1

Gene Name : com1
Sequence Strain (Species/Organism) : Coxiella burnetii
NCBI Protein GI : AAG41990
Other Database IDs : CDD:224565
CDD:239321
Taxonomy ID : 777
Protein Name : 27kDa outer membrane protein
Protein pI : 9.36
Protein Weight : 25255.8
Protein Length : 320
Protein Note : Protein-disulfide isomerase [Posttranslational modification, protein turnover, chaperones]; COG1651

Protein Sequence : Show Sequence

>AAG41990.1 27kDa outer membrane protein, partial [Coxiella burnetii]
MKNRLTALFLAGTLTAGVAIAAPSQSSFSPQQVKDIQSIVHHYLVNHPEVLVEVSQALQKKTEAQQEEHA
QQAIKENAKKLFNDPASPVAGNPHGNVTLVEFFDYQCGHCKAMNSVIQAIVKQNKNLRVVFKELPIFGGQ
SQYAAKVSLAAAKQGKYYAFHDALLSVDGQLSEQITLQTAEKVGLNVAQLKKDMDNPAIQKQLRDNFQLA
QSLQLAGTPTFVIGNKALTKFGFIPGATSQQNLQK

Molecule Role : Protective antigen
Molecule Role Annotation : (Jiao et al., 2014)

3. enhA1

Gene Name : enhA1
Sequence Strain (Species/Organism) : Coxiella burnetii Q321]
NCBI Protein GI : EDR35563
Taxonomy ID : 360117
Protein Name : enhanced entry protein EnhA
Protein pI : 8.37
Protein Weight : 26088.62
Protein Length : 312
Protein Note : identified by match to protein family HMM PF03734

Protein Sequence : Show Sequence

>EDR35563.1 enhanced entry protein EnhA [Coxiella burnetii Q321]
MERAIFIVLVSLLGASIAFGADSPNEYYGTGLCGKSGFECIKVQRGQSWQNLFPDENQRDLVQRLNRTDT
YLYPGKTLAVPKDLKDATIYSISPFPLRIKKLGEKLIMVNQDQLAWGAYDPEGQLIKWGPISSGKNYCRD
VNRSCETITGIFYVFHKKGPGCKSNVFPVETSGGAVMPYCMFFFKGYALHGSNEVTGYRDSHGCVRLFKR
DAKWLNENFVNVATKDGHLGTKVVVEKLTIGE

Molecule Role : Protective antigen
Molecule Role Annotation : (Wang et al., 2013)

4. htpB

Gene Name : htpB
Sequence Strain (Species/Organism) : Coxiella burnetii
VO ID : VO_0010934
NCBI Protein GI : 197253489
Locus Tag : AY251297
Other Database IDs : CDD:234573
CDD:237231
CDD:239460
Taxonomy ID : 777
Gene Strand (Orientation) : ?
Protein Name : heat shock protein B
Protein pI : 4.88
Protein Weight : 51650.62
Protein Length : 612
Protein Note : chaperonin GroEL; Reviewed; PRK00013

DNA Sequence : Show Sequence

>gi|30142089|gb|AY251297.1| Coxiella burnetii strain Xinqiao heat shock protein B (htpB) gene, complete cds
ATGGCTGCAAAAGTTTTAAAATTTTCCCACGAGGTATTACACGCAATGAGTCGTGGCGTGGAAGTTTTGG
CCAACGCGGTAAAAGTGACGTTGGGACCAAAAGGTCGCAATGTCGTTTTAGATAAATCATTTGGCGCACC
AACCATTACTAAAGACGGCGTTAGCGTAGCTAAAGAAATCGAGTTGGAAGACAAATTTGAAAATATGGGC
GCTCAAATGGTTAAAGAAGTGGCTTCGCGTACATCAGACGATGCGGGTGATGGTACCACAACAGCGACCG
TACTGGCTCAAGCGATTTTGGTTGAAGGCATCAAAGCCGTTATTGCTGGAATGAACCCCATGGATTTGAA
ACGGGGTATTGATAAAGCCGTAACGGCAGCGGTAGCTGAATTGAAGAAAATTTCCAAGCCTTGCAAAGAC
CAGAAAGCGATTGCGCAAGTAGGCACCATTTCTGCGAATTCGGATAAGTCGATTGGAGATATTATTGCGG
AAGCGATGGAGAAAGTGGGCAAAGAAGGCGTCATAACAGTAGAAGATGGCTCTGGTCTTGAAAACGCGCT
TGAAGTAGTTGAAGGTATGCAGTTCGATCGTGGTTACTTGTCGCCATACTTTATCAACAATCAACAAAAC
ATGAGTGCGGAGCTTGAAAATCCGTTTATCTTATTGGTTGACAAGAAGATTTCTAATATTCGTGAACTCA
TTCCGTTGTTAGAAAACATAGCAAAGTCTGGTCGGCCCTTATTGGTGATTGCCGAAGATATCGAAGGCGA
AGCTTTAGCGACGTTAGTGGTTAATAATATTCGCGGTGTTGTTAAAGTCGCGGCTGTAAAAGCACCTGGC
TTTGGCGATCGTCGTAAAGCGATGTTGCAAGATATTGCTGTTTTGACGGGCGGTAAGGTTATTTCTGAAG
AAGTCGGATTGTCCCTTGAGGCCGCTTCTTTGGATGATTTAGGTTCTGCTAAACGCGTTGTTGTCACTAA
AGATGACACCACCATCATTGATGGTTCTGGTGACGCCGGTGACATTAAAAACCGCGTGGAGCAAATCCGA
AAAGAAATAGAAAATAGCTCGTCGGACTATGATAAAGAGAAATTACAAGAACGTCTGGCAAAATTAGCCG
GTGGTGTGGCGGTCATTAAAGTGGGCGCTGCGACTGAAGTTGAAATGAAAGAGAAAAAAGCCCGCGTGGA
AGATGCCTTACATGCGACGCGCGCAGCCGTCGAAGAAGGTGTCGTACCGGGTGGTGGCGTTGCTTTAATC
CGCGTGCTTAAATCGCTTGATTCAGTGGAAGTTGAGAATGAAGACCAACGCGTGGGCGTGGAAATTGCTC
GCCGTGCGATGGCTTACCCGCTTTCTCAAATCGTGAAAAACACGGGTGTTCAAGCAGCCGTTGTCGCTGA
CAAAGTCTTGAACCATAAAGACGTTAATTATGGTTATAACGCAGCGACGGGTGAATACGGTGACATGATT
GAGATGGGTATTCTCGACCCAACCAAAGTGACCCGCACCGCGTTGCAAAACGCAGCTTCTATCGCTGGTC
TTATGATTACCACCGAATGTATGGTAACAGAAGCTCCCAAGAAGAAAGAGGAGTCGATGCCCGGCGGCGG
TGACATGGGCGGCATGGGAGGAATGGGCGGCATGGGCGGCATGATGTAA

Protein Sequence : Show Sequence

>ACH54112.1 heat shock protein B, partial [Coxiella burnetii]
AAKVLKFSHEVLHAMSRGVEVLADAVKVTLGPKGRNVVLDKSFGAPTITKDGVSVAKEIELEDKFENMGA
QMVKEVASRTSDDAGDGTTTATVLAQAILVEGIKAVIAGMNPMDLKRGIDKAVTAAVAELKKISKPCKDQ
KAIAQVGTISANSDKSIGDIIAEAMEKVGKEGVITVEDGSGLENALEVVEGMQFDRGYLSPYFINNQQNM
SAELENPFILLVDKKISNIRELIPLLENVAKSGRPLLVIAEDIEGEALATLVVNNIRGVVKVAAVKAPGF
GDRRKAMLQDIAVLTGGKVISEEVGLSLEAASLDDLGSAKRVVVTKDDTTIIDGSGDAGDIKNRVEQIRK
EIENSSSDYDKEKLQERLAKLAGGVAVIKVGAATEVEMKEKKARVEDALHATRAAVEEGVVPGGGVALIR
VLKSLDSVEVENEDQRVGVEIARRAMAYPLSQIVKNTGVQAAVVADKVLNHKDVNYGYNAATGEYGDMIE
MGILDPTKVTRTALQNAASIAGLMITTECMVTEAPKKKEESMPGGGDMGGM

Molecule Role : Protective antigen
Molecule Role Annotation : The purified recombinant proteins, P1, HspB, and P1-HspB, and whole-cell antigen (WCA) of C. burnetii were used to immunize BALB/c mice. Protective immunity against Q fever was induced with a recombinant P1 antigen fused with HspB after Coxiella burnetii challenge (Li et al., 2005).

This result showed that these proteins had the ability to evoke a humoral immune response and yield specific antibodies whose reactivity increased gradually with the progression of the infection. In addition, 15 proteins on the array had higher FI values than the Coxiella outer membrane protein 1 (Com1), which is the first surface protein antigen of C. burnetii recognized by Q fever sera. This suggests that these proteins might be major seroreactive antigens of C. burnetii. (Wang et al., 2013)
Related Vaccine(s): P1-HspB (fusion of protein 1 and heat-shock protein B)

5. icmO

Gene Name : icmO
Sequence Strain (Species/Organism) : Coxiella burnetii CbuK_Q154
NCBI Protein GI : ACJ20972
Other Database IDs : CDD:328724
Taxonomy ID : 434924
Protein Name : IcmO
Protein pI : 7.02
Protein Weight : 85095.33
Protein Length : 852
Protein Note : P-loop containing Nucleoside Triphosphate Hydrolases; cl21455

Protein Sequence : Show Sequence

>ACJ20972.1 IcmO [Coxiella burnetii CbuK_Q154]
MAYQPRGLEEKHERFHSHVLRDTRTLSVRMADFLKNPRGIATFLLLLAIITFFISYFSDVILLLGIGSFI
YTYTRKYKLPFRLPQHSHMKDYNDPLPGTRNKPRQAQGIYYFGNEGRTKEELWFSNEDMRTHVLIFGSTG
SGKTEAMVSIAYNALLQASGFIYVDGKGDNSLFAKVFSMVRSMGREDDLLLINFMTGAKDIIGPQEKRLS
NTLNPFANGSSSMLSQLIVSMMDKAAGTPDGDMWKGRAIAFTEALMKILVAMRDAGHILLDANTIRNYFH
LPKLEAIVVDKLFLREGEEPINLENVPPTVIEPIVNYVLTLPGYNKEKKGKQVSQVLEQHGFITMQLVRV
FTSLADTYGHIMRTNLAEVDLRDVVLNRRILCVLLPALEKSPDELSNLGKVIVSTLKAMMASGLGEHVEG
EYSDLVDAKPTNSKTPFLCVLDEYGYYAVEGFAVVPAQARSLGFSIIFAGQDLPAFQKASKEEAASIGAN
TNIKVCMKLEDPTETWDFFMKSAGESYVTHVESFQVDQGSVLGTYQDGRGARVEKRARIDLLDLKEQRQG
EAHFFFKSKIVRGKFFYADPKRTKHLRLNHFLKVEGPSDSEAKKLIKSFEHFEKLATKDTIFSDVEASNE
EVEKVSQVFSEETHLAPFDRSIIALKKFFTQTGDIPTSFLQELSASQKEDVDYLSLFTPLRLSDHIKEVV
ISSDLDNFKKPILDRAYLRDQIEYIQRLCGKSSQQAMNIAVELISDMEKGTRYPPKVDFTLKETDVAEGI
RDMIQAISLKKKEAAEKADNKS

Molecule Role : Protective antigen
Molecule Role Annotation : (Wang et al., 2013)

6. mip

Gene Name : mip
Sequence Strain (Species/Organism) : Coxiella burnetii
NCBI Protein GI : AAA92352
Other Database IDs : CDD:279662
CDD:223619
CDD:278674
Taxonomy ID : 777
Gene Strand (Orientation) : ?
Protein Name : peptidyl propyl cis/trans isomerase
Protein pI : 10.36
Protein Weight : 24628.84
Protein Length : 303
Protein Note : Domain amino terminal to FKBP-type peptidyl-prolyl isomerase; pfam01346

Protein Sequence : Show Sequence

>AAA92352.1 peptidyl propyl cis/trans isomerase [Coxiella burnetii]
MKRLILPFLSVGLLLGTTAHAATPLKTEQDKLSYSMGVMTGKAFRKHDIKIDPQTFSMGLSDAYLGKETQ
MTEAEMRQTLQQFEKQSLQKMQHKMKQTAQQNAEKSRAFLTANKNKPGVKTLANGLQYKVLQAGQGQSPT
LNDEVTVNYEGRLINGTVFDSSYKRGNPATFPLKSVIKGWQEALTRMKPGAIWEIYVPPQLAYGEQGAPG
VIGPNEALIFKVNLISVKKK

Molecule Role : Protective antigen
Molecule Role Annotation : (Xiong et al., 2014)

7. OmpA

Gene Name : OmpA
Sequence Strain (Species/Organism) : Coxiella burnetii
NCBI Protein GI : WP_041952488
Other Database IDs : CDD:225439
CDD:143586
Taxonomy ID : 777
Protein Name : OmpA family protein
Protein pI : 10.41
Protein Weight : 22612.03
Protein Length : 273
Protein Note : Outer membrane protein OmpA and related peptidoglycan-associated (lipo)proteins [Cell wall/membrane/envelope biogenesis]; COG2885

Protein Sequence : Show Sequence

>WP_041952488.1 OmpA family protein [Coxiella burnetii]
MRTKHVLSVKQTSHSPYEAKRDTGIASFRFVSTGLLLALGMSLSACSSYTTVSSAPVYTIPAPKPSLAKI
RAHYIHRLQADGVQVIKLGETMRFVLLSDCLFKPDSANLRSDYRPTLKALARLMKTYDKVNVQVAAYTDN
NGHIERQQALTTRQAQVVASFLWSRGINARLAYAVGYNRKNPVDYNGSSHGRFNNRRVEISFRFYPEYVP
YA

Molecule Role : Protective antigen
Molecule Role Annotation : (Xiong et al., 2014)

8. p1

Gene Name : p1
Sequence Strain (Species/Organism) : Coxiella burnetii
VO ID : VO_0010930
NCBI Protein GI : ACJ19787
Locus Tag : AY249911
Other Database IDs : ncbi protein accession number: AAP04425.1
Taxonomy ID : 434924
Gene Strand (Orientation) : ?
Protein Name : outer membrane porin P1
Protein pI : 7.87
Protein Weight : 25162.44
Protein Length : 321
Protein Note : phase I

DNA Sequence : Show Sequence

>gi|30025840|gb|AY249911.1| Coxiella burnetii strain Xinqiao outer membrane protein P1 gene, complete cds
ATGGAAACAACTACAAAACTCGCCATAGGCGTTTCTGCACTATGCTGCTTAGCCAGCGCTGCCTTTGCTG
GCGGTCCTGATATCCCCATGATTGATATGAATGGTTTTCATATCGGTTTGGGTTTTGGATATAAATCTTA
TACCTATGATCAGGTCGGAACCGTTACAGTTACTACTAATGGGGGCACTGTTCTGAGCGTGCTTCACCCA
GTTTCTGCTTCAATAACCCAATCTGGTCCTGTCGGTGAATTAGGTTATACCTTCGCAAGTGACTGGTGGA
TAGCAGGTGTTAAGGCTCAATACCAGTACGATAACGTACGAAGCGTCCACATAATGGATGCACCTTTAGT
AGGTTCTAATTATTCTTATCGAATCCGTTTGGGTTCCCACTTTACTGCTATGCTGTTAGCAGGTATTAAA
GTAAACGAAGCTAATGCTGTTTACTTAGAAGCCGGTTATTCGACAGTGTGGGGGAAAACTACCCTCTTTG
GTCCTGGCCCAGTTGCAGTTAGTATAAAGAATCGGCTGAACGGTGGTATCGCTGGTATCGGTTGGAGACA
TTATTTTATGAACAATGTCTTTCTTGATCTTAGCTATGACTACGCATTGTATAGAAGTAAATCCAATAGC
GTAACTCTCTCTTCAGCTACTGCTTCAGCAGAAGGGACGGCGATTGGCGTTTCAGGAACTGTTCAAAATC
CGAAACGAGTCGCAATTAACGGCATTACCGCAACCGTTAATTACCTGTTCAATATCTAA

Protein Sequence : Show Sequence

>ACJ19787.1 outer membrane porin P1 [Coxiella burnetii CbuK_Q154]
METTTKLAIGVSALCCLASAAFAGGPDIPMIDMNGFHIGLGFGYKSYTYDQVGTVTVTTDGGTILSVLHP
VSASITQFSPVGELGYTFASDWWIAGVKAQYQYDNVRSVHIMDASLVGSTYRTRLGSHLTAMLLAGIKVN
EANAVYLEAGYSTVWGKTTLFGPGPVAVSMKNRLNGGIAGIGWRHYFMNNVFLDLSYDYALYRSKSNSVT
LSSATASAEEAAIGVLGTVQNPKRVAINGITATVNYLFNI

Molecule Role : Protective antigen
Molecule Role Annotation : The purified recombinant proteins, P1, HspB, and P1-HspB, and whole-cell antigen (WCA) of C. burnetii were used to immunize BALB/c mice. Protective immunity against Q fever was induced with a recombinant P1 antigen fused with HspB after Coxiella burnetii challenge (Li et al., 2005).

The identification of 37 SEPs and show that 30 react with sera from mice immunized with Cox. burnetii and sera from patients with Q fever. (Jiao et al., 2014)
Related Vaccine(s): P1-HspB (fusion of protein 1 and heat-shock protein B)

9. ybgF

Gene Name : ybgF
Sequence Strain (Species/Organism) : Coxiella burnetii
NCBI Protein GI : RQM80114
Other Database IDs : CDD:292947
CDD:188247
CDD:276809
CDD:276939
Taxonomy ID : 777
Gene Strand (Orientation) : ?
Protein Name : tol-pal system protein YbgF
Protein pI : 7.56
Protein Weight : 34027.54
Protein Length : 371
Protein Note : Derived by automated computational analysis using gene prediction method: Protein Homology.

Protein Sequence : Show Sequence

>RQM80114.1 tol-pal system protein YbgF [Coxiella burnetii]
MRLIKMKIKTLCVSSALAALMLSAPLTWADAPVEDISAQPQPTKTTVSRSETPETAIPTAPVSLPTTQTD
LTVTHRLARLEQQLNNIINMNLPQQISDLQQQLAQVRGQLQVQERNLELLNNQQRSFYRDLDQRITQLKN
LNSNNSDSSNDNSASSSQKPSSGDTSNTNNIQLQDSNTYRQALDLLTKKQYDKAQASFQNYLNDYPNGSY
VANAHYWLGEIYLQQKDRKNAAHEFQTVRDKFPKSEKVLDAKLKLAIIDAEDGKIKQAKEELTEIKKQHP
ESTAAQLANIRLQQLEEVDSATTTP

Molecule Role : Protective antigen
Molecule Role Annotation : (Jiao et al., 2014)

III. Vaccine Related Host Genes

1. IgM (partial)

Gene Name : IgM (partial)
Sequence Strain (Species/Organism) : Homo sapiens
NCBI Protein GI : 1020017
Other Database IDs : CDD:143181
CDD:203725
Taxonomy ID : 9606
Gene Strand (Orientation) : ?
Protein Name : IgM
Protein Length : 112
Protein Note : Immunoglobulin (Ig) light chain, kappa type, variable (V) domain; cd04980

Protein Sequence : Show Sequence

>gi|1020017|gb|AAC41922.1| IgM, partial [Homo sapiens]
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTE
FTLTISSLQSEDFAVYYCQQYNNWPPWTFGQGTKVEIKRTVA

Molecule Role : Vaximmutor
Related Vaccine(s): Chloroform-methanol residue (CMR)

IV. Vaccine Information

1. Chlamyvax FQ

a. Tradename:

Chlamyvax-FQ

b. Vaccine Ontology ID:

VO_0004135

c. Type:

Inactivated or "killed" vaccine

d. Preparation

Chlamyvax FQ is prepared as an oil emulsion with Chlamydophila abortus and phase II C. burnetii.

e. Description

Chlamyvax FQ is an inactivated phase II vaccine commercially available in France (Arricau-Bouvery et al., 2005).

f. Goat Response

Vaccination Protocol: Two groups of goat (one- and two year-old) were immunized subcutaneously with either Chlamyvax FQ or Coxevac six weeks before mating. Three weeks after initial vaccination, a booster dose was injected. A group of unvaccinated goats served as the control (Arricau-Bouvery et al., 2005).
Immune Response: After the goats were vaccinated and before the challenge, the antibody response was lower in the group vaccinated with Chlamyvax FQ than the group vaccinated with phase I vaccine Coxevac. This showed that the phase II vaccine antigens were less immunogenic than phase I vaccine antigens. About 7 weeks after challenge, goats vaccinated with Chlamyvax FQ had higher antibody rates than those of goats vaccinated with Coxevac, indicating that the phase II vaccine Chlamyvax FQ was not sufficient in controlling bacterial infection (Arricau-Bouvery et al., 2005).
Challenge Protocol: The groups of goats were challenged with 10^4 infective mouse doses (I.M.D.) of CbC1 strain C. burnetii 105 days after booster dose, injected subcutaneously in the front right shoulder (Arricau-Bouvery et al., 2005).
Efficacy: Chlamyvax FQ did not show effectiveness in protection against abortion and C. burnetii shedding in milk, feces, placenta, and vaginal secretions. Results showed that 87% and 93.3% of the goats vaccinated with Chlamyvax FQ had abortion and contaminated placenta, respectively. These figures were comparable with the data from the control group without vaccination (Arricau-Bouvery et al., 2005).

2. Chloroform-methanol residue (CMR)

a. Vaccine Ontology ID:

VO_0004132

b. Type:

chloroform-methanol residue vaccine

c. Preparation

The CMR vaccine is prepared from chloroform-methanol residue of Formalin-killed whole cells of C. burnetii. C. burnetii whole cells are lyophilized and refluxed with CM azeotrope of 4:1. 150 mg of whole cells are then added to 100 ml of CM, which is then refluxed for 6 to 8 hours. Cellular material is separated by filtration and the residue on filter is mixed with 100 ml of CM. After three repetitions, the filtrate (extractable component) is the CME and the residue (particulate material) is the CMR (Williams and Cantrell, 1982).

d. Description

The CMR vaccine consists of chloroform-methanol residues from killed whole cells of C. burnetii.

e. Monkey Response

Host Strain: Adult cynomolgus monkeys
Vaccination Protocol: Two groups of 10 monkeys (2.0 to 6.0 kg in weight) were immunized with 30 μg of CMR subcutaneously. Single groups were immunized with 30 μg of Q-Vax, or 100 μg of CMR, or placebo subcutaneously.The group initially given 30 μg of CMR was given a booster of another 30 μg of CMR after twenty-eight days (Waag et al., 2002).
Persistence: The antibody responses at single 100 μg dose of CMR and two 30 μg doses of CMR were short-lived. Anti-phases I and II antibody levels dropped to baseline levels at the 17th week after immunization (Waag et al., 2002).
Immune Response: A single 30 μg dose of CMR and a single 30 μg dose of Q-Vax resulted in similar antibody responses. The 100 μg single CMR dose and the two 30 μg doses of CMR increased the immunogenicity of the vaccine, but the antibody responses were short-lived. Anti-phases I and II antibody responses rose at equal magnitude and antibody titers leveled off 2 weeks after challenge for the vaccinated monkeys. In contrast, control monkeys had a higher anti-phase II response than anti-phase I response. Within three weeks, monkeys in control group had anti-phase II response that was greater than that in the vaccinated monkeys (Waag et al., 2002).
Side Effects: Monkeys challenged six months after vaccination showed signs of illness. However, the illnesses were less severe and/or of shorter duration for the vaccinated monkeys than for the control monkeys. A majority of the control monkeys had increases in interstitial and bronchial opacity (as opposed to only a minority of vaccinated monkeys showing those changes). A drop in hemaglobin and hematocrit was observed in all groups. All monkeys, besides groups vaccinated with single dose 100 μg CMR or two 30 μg doses of CMR, were bacteremic, which correlated with fever (Waag et al., 2002).
Challenge Protocol: After six months of initial immunization, the monkeys were challenged with approximately 10^5 virulent phase I Henzerling strian C. burnetii administered using aerosol (Waag et al., 2002).
Efficacy: The study showed that CMR and Q-Vax were equally efficacious and immunogenic in monkeys challenged by aerosol (Waag et al., 2002).
Description: This study investigated the vaccine efficacy of CMR and Q-Vax in monkeys challenged by aerosol, which resembles the route of human infection (Waag et al., 2002).

f. Guinea pig Response

Host Strain: Hartley guinea pigs
Vaccination Protocol: Groups of seven 250-300 g Hartley guinea pigs were vaccinated subcutaneously with 0.5 ml of 0.003, 0.03, 0.3, 3, or 30 μg of CMR. Guinea pigs in control groups were given USP saline (Waag et al., 1997).
Immune Response: None reported
Side Effects: None reported
Challenge Protocol: Six weeks from vaccination, the guinea pigs were challenged with10-fold 50% infection dose of phase I Henzerling strain C. burnetii administered in a small particle aerosol (Waag et al., 1997)
Efficacy: 0.003 and 0.03 μg dose did not effectively protect the pigs from infection. Guinea pigs vaccinated with 0.3, 3.0, or 30.0 μg CMR were significantly protected compared to the groups injected with USP saline (Waag et al., 1997).

g. Mouse Response

Host Strain: A/J
Vaccination Protocol: Groups of ten six-week-old A/J strain female mice were immunized with 0.5 ml of 0.01, 0.1, or 1.0 μg of CMR. Mice in control groups were given USP saline (Waag et al., 1997).
Immune Response: None reported
Side Effects: None reported
Challenge Protocol: Six weeks from vaccination, the mice were challenged with10-fold 50% infection dose of phase I Henzerling strain C. burnetii administered in a small particle aerosol (Waag et al., 1997).
Efficacy: Mice vaccinated with 0.01 or 0.1 μg of CMR were not protected. However, the 1.0 μg dose of CMR were effective in protecting the mice from infection (Waag et al., 1997).

h. Mouse Response

Host Strain: C57BL/10ScN mice
Vaccination Protocol: Endotoxin nonresponder male mice (C57BL/10ScN, 8 to 10 weeks old) in experimental groups of 5 to 10 were given a single injection of 30 or 300 μg of killed cells, CMR, or CME (Williams and Cantrell, 1982).
Immune Response: High titers of phase II antibodies were detected with mice immunized with CMR.Similar detection was found for killed cells treated mice. However, there was a lower level of phase I antibodies for CMR treated mice than killed whole cells treated mice. Neither phase I nor phase II antibodies was found for mice immunized with CME (Williams and Cantrell, 1982).
Side Effects: No side effects of splenomegaly, hepatomegaly, or liver necrosis were observed for mice treated with CMR or CME. However, the mice group treated with killed whole cells showed severe, life-threatening side effects (Williams and Cantrell, 1982).
Challenge Protocol: Fourteen or thirty days after vaccination, the mice were challenged with 7 x 10^10 PFU of viable organisms of phase I C. burnetii Ohio strain (Williams and Cantrell, 1982).
Efficacy: Mice immunized with 30 μg of CMR resulted in higher protection (70% to 90%) than mice inoculated with killed whole cells (which was 50%). However, mice immunized with 300 μg CME had only 10% survival rate (Williams and Cantrell, 1982).

i. Human Response

Host Strain: Volunteers without cardiovascular, pulmonary, hepatitis, renal, or immunologic disease or without hepatitis B virus or HIV type 1 infection or without receiving any immunosuppressive medication
Vaccination Protocol: Human subjects were randomly assigned to receive either vaccine or placebo in a ratio of 5:2. Groups of five subjects were immunized with 30, 60, or 120 μg of CMR at one-week intervals. Twenty subjects then received 240 μg of CMR. Each group had corresponding placebo recipients in the 5:2 ratio. Subjects’ temperatures were checked on days 1, 2, 3, 7, 15, and 30 with blood specimens obtained 15, 30, 90, and 180 days after immunization. Vaccine immunogenicity were assayed with kinetic enyzme-linked immunosorbent assay (KELISA) (Fries et al., 1993).
Immune Response: CMR induced the greatest IgM responses. IgM responses to phase I antigen were similar while the IgM responses to phase II antigen were less frequent. IgG responses were less common to CMR, phase I, and phase II antigens (Fries et al., 1993).
Side Effects: CMR at 30 and 60 μg caused minimal side effects. Higher doses of CMR caused reactions similar to those cause by 30 μg of whole-cell vaccines. 120 μg and 240 μg dose induced local erythema in 5 (out of 15) and 8 (out of 10) recipients and subcutaneous induration in 4 (out of 15) and 7 (out of 10) recipients, respectively (Fries et al., 1993).
Challenge Protocol: Subjects were not challenged (Fries et al., 1993).
Description: CMR vaccine could be safely administered to human subjects unscreened for prior C. burnetii immunity with acceptable local reactions at 30 to 120 μg doses (Fries et al., 1993).
Host Gene Response of IgM (partial)
- Gene Response: CMR induced the greatest serum IgM responses. IgM responses to phase I antigen were similar while the IgM responses to phase II antigen were less frequent. The group receiving 240 micrograms had significantly higher responses than the placebo group at all post immunization time points. The 120-microgram dose group approached significant difference from placebo recipients at days 30, 90, and180 post immunization ( (Fries et al., 1993).
- Detailed Gene Information: Click here.

3. Coxevac

a. Tradename:

Coxevax

b. Vaccine Ontology ID:

VO_0004134

c. Type:

Inactivated or "killed" vaccine

d. Preparation

Coxevac vaccine is prepared with Nine Mile strain of C. burnetii in yolk sacs of pathogen-free embryonated hen eggs. The vaccine consists of purified formaldehyde inactivated phase I C. burnetii corpuscular antigens. It is standardized at 100 μg of antigens in 1 ml. The vaccine is then preserved by thiomersale (Arricau-Bouvery et al., 2005).

e. Description

Coxevac vaccine is an inactivated phase I vaccine commercially available in Slovakia (Arricau-Bouvery et al., 2005).

f. Goat Response

Vaccination Protocol: One group of goat (one- and two year-old) were immunized subcutaneously with either Coxevac or Chlamyvax FQ six weeks before mating. Three weeks after initial vaccination, a booster dose was injected. A group of unvaccinated goats served as the control (Arricau-Bouvery et al., 2005).
Immune Response: After the goats were vaccinated and before the challenge, the antibody response was higher in the group vaccinated with Coxevac than the group vaccinated with phase II vaccine Chlamyvax FQ. This showed that the phase I vaccine antigens were more immunogenic than phase II vaccine antigens. About 7 weeks after challenge, goats vaccinated with Coxevac had lower antibody rates than those of goats vaccinated with Chlamyvax FQ, indicating that the phase I vaccine Coxevac was more sufficient in controlling bacterial infection (Arricau-Bouvery et al., 2005).
Challenge Protocol: The groups of goats were challenged with 10^4 infective mouse doses (I.M.D.) of CbC1 strain C. burnetii 105 days after booster dose, injected subcutaneously in the front right shoulder (Arricau-Bouvery et al., 2005).
Efficacy: Coxevac showed significant protection against abortion and C. burnetii shedding in milk, feces, placenta, and vaginal secretions. Results showed that 75% and 100% of the control goats had abortion and contaminated placenta, respectively. In comparison, only 6% and 37.5% of the goats vaccinated with Coxevac had abortion and contaminated placenta, respectively (Arricau-Bouvery et al., 2005).

4. M-44

a. Vaccine Ontology ID:

VO_0004131

b. Type:

Live, attenuated vaccine

c. Preparation

Crude rickettsial pools are produced in embryonated eggs of hens free from avian leucosis virus. The embryonated eggs are inoculated with 0.2 ml of seed stock containing 10^7.9 median infectious doses at 35C. After 6 to 7 days, the yolk sacs are collected and diluted to a 50% suspension with distilled water. The strains are then obtained through purification using alternating low-speed and high-speed centrifugations. After centrifugation, the pellet is suspended in 10% sucrose and centrifuged onto a 70% sucrose solution. The purified strains are then obtained from the surface and diluted with Snyder I buffer to result in a final titer of 10^9.5 median infectious dose per ml and freeze-dried (Robinson and Hasty, 1974).

d. Description

M-44 vaccine is developed from attenuated phase II M-44 strain of C. burnetii (Robinson and Hasty, 1974).

e. Guinea pig Response

Host Strain: Hartley guinea pigs
Vaccination Protocol: Hartley guinea pigs (250 to 350 g) were immunized intraperitoneally or subcutaneously with serial 10-fold dilutions (prepared in physiological buffered saline) of M-44 vaccine (Robinson and Hasty, 1974).
Immune Response: Vaccine at high doses prevented anamnestic-type response (Robinson and Hasty, 1974).
Challenge Protocol: Guinea pigs were challenged with either phase I or phase II C. burnetii (Robinson and Hasty, 1974).
Efficacy: 10^2 median infectious dose protected the guinea pigs from death, but did not protect the animals from febrile effects of challenge. Protections against the febrile effects of the challenge of phase I C. burnetii were observed at vaccines doses of 10^4 median infectious dose or greater. Protections against the febrile effects of the challenge of phase II C. burnetii were observed at vaccine doses of 10^3 median infectious dose or greater (Robinson and Hasty, 1974).

5. P1-HspB (fusion of protein 1 and heat-shock protein B)

a. Vaccine Ontology ID:

VO_0004133

b. Type:

Subunit vaccine

c. Gene Engineering of p1

Type: Recombinant protein preparation
Description: The primers were synthesized and the target DNA fragments were amplified by PCR from C. burnetii genomic DNA. The mixture used during amplification consisted of 0.3 M primer, 200 M deoxynucleoside triphosphate, and 0.6 U of Taq polymerase (Li et al., 2005). See preparation below for more information.
Detailed Gene Information: Click here.

d. Gene Engineering of htpB

Type: Recombinant protein preparation
Description: The primers were synthesized and the target DNA fragments were amplified by PCR from C. burnetii genomic DNA. The mixture used during amplification consisted of 0.3 M primer, 200 M deoxynucleoside triphosphate, and 0.6 U of Taq polymerase (Li et al., 2005). See preparation below for more information.
Detailed Gene Information: Click here.

e. Adjuvant:

VO ID: VO_0000139

f. Adjuvant:

VO ID: VO_0000142

g. Preparation

Gene fragments encoding C. burnetii outer membrane protein 1 (P1) and heat-shock protein B (HspB) are amplified by PCR from genomic DNA extracted from C. burnetii. The amplified p1 and hspB gene fragments are purified and digested with DNA endonuclease pairs BamHI/ScaI and SacI/PstI, respectively. The genes are then ligated with pQE30 (digested with homologous enzyme pair) with T4 ligase, resulting in recombinant expression plasmids pQE30/p1 and pQE30/hspB. Plasmid pQE30/p1-hspB is constructed by ligating hspB of pQE30/hspB with p1 fragment from pQE30/p1. E.coli M15 cells are then transformed with the ligation mixtures and screened on medium containing ampicillin and kanamycin. The E. coli cells were propagated in LB medium and induced by IPTG. The resulting recombinant proteins were purified by affinity chromatography with nickel-nitrilotriacetic resin (Li et al., 2005).

h. Mouse Response

Host Strain: BALB/c
Vaccination Protocol: Mice (six to eight weeks old) were immunized subcutaneously with 30 μg of purified P1, HspB, P1-HspB, or whole-cell antigen with Freund's complete adjuvant. After four weeks, the mice were then immunized intraperitoneally twice every two weeks with 15 μg of homologous antigen with Freund's incomplete adjuvant (Li et al., 2005).
Immune Response: HspB was found to be efficient in eliciting humoral immunoresponses while P1 was found to be efficient in eliciting cell-mediated immunoresponses. There was higher antibody titer for HspB-ummunized mice than that for P1-immunized mice.
Challenge Protocol: Eight weeks and ten days from after initial immunization, each group of mice was challenged with10-fold 50% infection dose of C. burnetii. After seven days, mice's spleens were removed and evaluated.
(Li et al., 2005).
Efficacy: P1-HspB fusion protein provided a better protection against C. burnetii than that offered by P1 or HspB alone (Li et al., 2005).

6. Q-VAX

a. Tradename:

Q-VAX

b. Vaccine Ontology ID:

VO_0004129

c. Type:

Inactivated or "killed" vaccine

d. Preparation

The formalin-inactivated vaccine is prepared from phase I Henzerling strain of Corxiella burnetii grown in the yolk sacs of embryonated eggs (Ackland et al., 1994).

e. Description

Q-VAX(R) is a formalin-inactivated phase I Corxiella burnetii. This vaccine is produced and licensed in Australia. It is currently the most effective vaccine in preventing Q fever (Ackland et al., 1994).

f. Monkey Response

Host Strain: Adult cynomolgus monkeys
Vaccination Protocol: Groups of 10 monkeys (2.0 to 6.0 kg in weight) were immunized with 30 μg of Q-Vax, or 100 μg of CMR, or placebo subcutaneously. Two groups were immunized with 30 μg of CMR subcutaneously. The group initially given 30 μg of CMR was given a booster of another 30 μg of CMR after twenty-eight days (Waag et al., 2002).
Immune Response: A single 30 μg dose of Q-Vax and a single 30 μg dose of CMR resulted in similar antibody responses. Anti-phases I and II antibody responses rose at equal magnitude and antibody titers leveled off 2 weeks after challenge for the vaccinated monkeys (for both Q-Vax and CMR). In contrast, control monkeys had a higher anti-phase II response than anti-phase I response. Within three weeks, monkeys in control group had anti-phase II response that was greater than that in the vaccinated monkeys (Waag et al., 2002).
Side Effects: Monkeys challenged six months after vaccination showed signs of illness. However, the illnesses were less severe and/or of shorter duration for the both Q-Vax and CMR vaccinated monkeys than for the control monkeys. A majority of the control monkeys had increases in interstitial and bronchial opacity (as opposed to only a minority of vaccinated monkeys showing those changes). A drop in hemaglobin and hematocrit was observed in all groups. All monkeys, besides groups vaccinated with single dose 100 μg CMR or two 30 μg doses of CMR, were bacteremic, which correlated with fever (Waag et al., 2002).
Challenge Protocol: After six months of initial immunization, the monkeys were challenged with approximately 10^5 virulent phase I Henzerling strian C. burnetii administered using aerosol (Waag et al., 2002).
Efficacy: The study showed that CMR and Q-Vax were equally efficacious and immunogenic in monkeys challenged by aerosol (Waag et al., 2002).
Description: This study investigated the vaccine efficacy of CMR and Q-Vax in monkeys challenged by aerosol (Waag et al., 2002). See Host Response (Host Name: Monkey) under Chloroform-methanol residue (CMR) for more descriptive detail on results of the groups vaccinated with CMR.

g. Mouse Response

Host Strain: A/J
Vaccination Protocol: Groups of ten six-week-old A/J strain female mice were immunized with 0.5 ml of 0.01, 0.1, or 1.0 μg of Q-Vax. Mice in control groups were given USP saline (Waag et al., 1997).
Immune Response: None reported
Side Effects: None reported
Challenge Protocol: Six weeks from vaccination, the mice were challenged with10-fold 50% infection dose of phase I Henzerling strain C. burnetii administered in a small particle aerosol (Waag et al., 1997).
Efficacy: Mice vaccinated with 0.01 or 0.1 μg of Q-Vax were not protected. However, the 1.0 μg dose of Q-Vax were effective in protecting the mice from infection (Waag et al., 1997).

h. Guinea pig Response

Host Strain: Hartley guinea pigs
Vaccination Protocol: Groups of seven 250-300 g Hartley guinea pigs were vaccinated subcutaneously with 0.5 ml of 0.003, 0.03, 0.3, 3, or 30 μg of Q-Vax. Guinea pigs in control groups were given USP saline (Waag et al., 1997).
Immune Response: None reported
Side Effects: None reported
Challenge Protocol: Six weeks from vaccination, the guinea pigs were challenged with10-fold 50% infection dose of phase I Henzerling strain C. burnetii administered in a small particle aerosol (Waag et al., 1997).
Efficacy: 0.003 and 0.03 μg dose did not effectively protect the pigs from infection. Guinea pigs vaccinated with 0.3, 3.0, or 30.0 μg Q-Vax were significantly protected compared to the groups injected with USP saline (Waag et al., 1997).

i. Human Response

Efficacy: Among the 2555 employees who were vaccinated, only two cases of Q fever were found. However, 55 cases were found among the 1365 unvaccinated employees. The two vaccinated employees had Q fever only within days of vaccination (before immunity was developed). Therefore, the protective efficacy of Q-Vax was 100% (Ackland et al., 1994).
Description: A survey of all vaccinated and unvaccinated employees who had Q fever at three abattoirs in Australia from 1985 to 1990 were studied (Ackland et al., 1994).

V. References

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