Coxiella burnetii 777 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). Q fever 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). 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). 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. Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 Chlamyvax FQ Chlamyvax-FQ VO_0004135 Inactivated or "killed" vaccine Chlamyvax FQ is an inactivated phase II vaccine commercially available in France (Arricau-Bouvery et al., 2005). Chlamyvax FQ is prepared as an oil emulsion with Chlamydophila abortus and phase II C. burnetii. 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). 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). 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). 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). Chloroform-methanol residue (CMR) VO_0004132 chloroform-methanol residue vaccine The CMR vaccine consists of chloroform-methanol residues from killed whole cells of C. burnetii. 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). 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). Adult cynomolgus monkeys 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). 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). The study showed that CMR and Q-Vax were equally efficacious and immunogenic in monkeys challenged by aerosol (Waag et al., 2002). 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). 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). 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). None reported Hartley guinea pigs 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). 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). None reported 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) None reported A/J 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). 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). None reported 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). 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). C57BL/10ScN mice 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). 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). 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). 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). 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). 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 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). 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). Subjects were not challenged (Fries et al., 1993). 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). 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). Coxevac Coxevax VO_0004134 Inactivated or "killed" vaccine Coxevac vaccine is an inactivated phase I vaccine commercially available in Slovakia (Arricau-Bouvery et al., 2005). 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). 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). 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). 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). 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). licensed Q fever human vaccine Generic Unknown VO_0000463 Inactivated or "killed" vaccine Licensed A generic representation of vaccines utilized to prevent Q fever in humans, most commonly formulated as inactivated whole-cell vaccines containing killed Coxiella burnetii. These vaccines are designed to induce immunity without causing disease by using non-viable bacterial cells. M-44 VO_0004131 Live, attenuated vaccine M-44 vaccine is developed from attenuated phase II M-44 strain of C. burnetii (Robinson and Hasty, 1974). 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). Vaccine at high doses prevented anamnestic-type response (Robinson and Hasty, 1974). Hartley guinea pigs 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). 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). Guinea pigs were challenged with either phase I or phase II C. burnetii (Robinson and Hasty, 1974). P1-HspB (fusion of protein 1 and heat-shock protein B) VO_0004133 Subunit vaccine Complete & incomplete Freund's adjuvant 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). Recombinant protein preparation 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. Recombinant protein preparation 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. 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. BALB/c 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). P1-HspB fusion protein provided a better protection against C. burnetii than that offered by P1 or HspB alone (Li et al., 2005). 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). Q-VAX Q-VAX VO_0004129 Inactivated or "killed" vaccine 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). 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). 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). Adult cynomolgus monkeys 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). The study showed that CMR and Q-Vax were equally efficacious and immunogenic in monkeys challenged by aerosol (Waag et al., 2002). 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). 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). 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. None reported A/J 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). 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). None reported 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). None reported Hartley guinea pigs 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). 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). None reported 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). 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). 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). htpB Coxiella burnetii VO_0010934 197253489 AY251297 CDD:234573 CDD:237231 CDD:239460 777 ? heat shock protein B 4.88 51650.62 612 chaperonin GroEL; Reviewed; PRK00013 >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 >ACH54112.1 heat shock protein B, partial [Coxiella burnetii] AAKVLKFSHEVLHAMSRGVEVLADAVKVTLGPKGRNVVLDKSFGAPTITKDGVSVAKEIELEDKFENMGA QMVKEVASRTSDDAGDGTTTATVLAQAILVEGIKAVIAGMNPMDLKRGIDKAVTAAVAELKKISKPCKDQ KAIAQVGTISANSDKSIGDIIAEAMEKVGKEGVITVEDGSGLENALEVVEGMQFDRGYLSPYFINNQQNM SAELENPFILLVDKKISNIRELIPLLENVAKSGRPLLVIAEDIEGEALATLVVNNIRGVVKVAAVKAPGF GDRRKAMLQDIAVLTGGKVISEEVGLSLEAASLDDLGSAKRVVVTKDDTTIIDGSGDAGDIKNRVEQIRK EIENSSSDYDKEKLQERLAKLAGGVAVIKVGAATEVEMKEKKARVEDALHATRAAVEEGVVPGGGVALIR VLKSLDSVEVENEDQRVGVEIARRAMAYPLSQIVKNTGVQAAVVADKVLNHKDVNYGYNAATGEYGDMIE MGILDPTKVTRTALQNAASIAGLMITTECMVTEAPKKKEESMPGGGDMGGM Protective antigen 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 [Ref621: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. [Ref4679:Wang et al., 2013] IgM (partial) Homo sapiens 1020017 CDD:143181 CDD:203725 9606 ? IgM 112 Immunoglobulin (Ig) light chain, kappa type, variable (V) domain; cd04980 >gi|1020017|gb|AAC41922.1| IgM, partial [Homo sapiens] EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTE FTLTISSLQSEDFAVYYCQQYNNWPPWTFGQGTKVEIKRTVA Vaximmutor p1 Coxiella burnetii VO_0010930 ACJ19787 AY249911 ncbi protein accession number: AAP04425.1 434924 ? outer membrane porin P1 7.87 25162.44 321 phase I >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 >ACJ19787.1 outer membrane porin P1 [Coxiella burnetii CbuK_Q154] METTTKLAIGVSALCCLASAAFAGGPDIPMIDMNGFHIGLGFGYKSYTYDQVGTVTVTTDGGTILSVLHP VSASITQFSPVGELGYTFASDWWIAGVKAQYQYDNVRSVHIMDASLVGSTYRTRLGSHLTAMLLAGIKVN EANAVYLEAGYSTVWGKTTLFGPGPVAVSMKNRLNGGIAGIGWRHYFMNNVFLDLSYDYALYRSKSNSVT LSSATASAEEAAIGVLGTVQNPKRVAINGITATVNYLFNI Protective antigen 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 [Ref621: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. 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