title: Immunoproteomically identified GBAA_0345, alkyl hydroperoxide reductase subunit C is a potential target for multivalent anthrax vaccine.
abstract: Anthrax is caused by the spore-forming bacterium Bacillus anthracis, which has been used as a weapon for bioterrorism. Although current vaccines are effective, they involve prolonged dose regimens and often cause adverse reactions. High rates of mortality associated with anthrax have made the development of an improved vaccine a top priority. To identify novel vaccine candidates, we applied an immunoproteomics approach. Using sera from convalescent guinea pigs or from human patients with anthrax, we identified 34 immunogenic proteins from the virulent B. anthracis H9401. To evaluate vaccine candidates, six were expressed as recombinant proteins and tested in vivo. Two proteins, rGBAA_0345 (alkyl hydroperoxide reductase subunit C) and rGBAA_3990 (malonyl CoA-acyl carrier protein transacylase), have afforded guinea pigs partial protection from a subsequent virulent-spore challenge. Moreover, combined vaccination with rGBAA_0345 and rPA (protective antigen) exhibited an enhanced ability to protect against anthrax mortality. Finally, we demonstrated that GBAA_0345 localizes to anthrax spores and bacilli. Our results indicate that rGBAA_0345 may be a potential component of a multivalent anthrax vaccine, as it enhances the efficacy of rPA vaccination. This is the first time that sera from patients with anthrax have been used to interrogate the proteome of virulent B. anthracis vegetative cells.
authors.affiliation: Division of High-risk Pathogen Research, Korea National Institute of Health, Chungbuk, Republic of Korea; School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Kyung Ae
authors.initials: KA
authors.lastname: Kim
authors.forename: Yu-Ri
authors.initials: YR
authors.lastname: Kim
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Choi
authors.forename: Hye Kyeong
authors.initials: HK
authors.lastname: Kim
authors.forename: Ki Ju
authors.initials: KJ
authors.lastname: Choi
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Chun
authors.forename: Kiweon
authors.initials: K
authors.lastname: Cha
authors.forename: Kee-Jong
authors.initials: KJ
authors.lastname: Hong
authors.forename: Na Gyong
authors.initials: NG
authors.lastname: Lee
authors.forename: Cheon-Kwon
authors.initials: CK
authors.lastname: Yoo
authors.forename: Hee-Bok
authors.initials: HB
authors.lastname: Oh
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
authors.forename: Gi-eun
authors.initials: GE
authors.lastname: Rhie
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D022122:Anthrax Vaccines / Q000737:chemistry / Q000276:immunology*; D001408:Bacillus anthracis / Q000201:enzymology* / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006168:Guinea Pigs; D015151:Immunoblotting; D054464:Peroxiredoxins / Q000737:chemistry / Q000276:immunology*; D040901:Proteomics; D016019:Survival Analysis
chemical_list: D022122:Anthrax Vaccines; D001426:Bacterial Proteins; D054464:Peroxiredoxins
keywords: Alkyl hydroperoxide reductase subunit C; Bacillus anthracis; Immunoproteomics; Microbiology; Vaccine