Immunoproteomically identified GBAA _0345, alkyl hydroperoxide reductase subunit C is a potential target for multivalent anthrax vaccine
Authors:
- 25 November 2013
- journal article
- research article
- Published by Wiley in Proteomics
- Vol. 14 (1) , 93-104
Abstract
Anthrax is caused by the spore‐forming bacterium B acillus 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 H 9401. To evaluate vaccine candidates, six were expressed as recombinant proteins and tested in vivo. Two proteins, r GBAA _0345 (alkyl hydroperoxide reductase subunit C ) and r GBAA _3990 (malonyl C o A ‐acyl carrier protein transacylase), have afforded guinea pigs partial protection from a subsequent virulent‐spore challenge. Moreover, combined vaccination with r GBAA _0345 and r PA (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 r GBAA _0345 may be a potential component of a multivalent anthrax vaccine, as it enhances the efficacy of r PA 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.Keywords
Funding Information
- Korea National Institute of Health (4840-300-210-13)
This publication has 55 references indexed in Scilit:
- Reverse Vaccinology: Developing Vaccines in the Era of GenomicsImmunity, 2010
- Anthrax vaccination strategiesMolecular Aspects of Medicine, 2009
- Bacillus anthracis physiology and geneticsMolecular Aspects of Medicine, 2009
- Recombinant Bacillus anthracis spore proteins enhance protection of mice primed with suboptimal amounts of protective antigenVaccine, 2008
- Recombinant Exosporium Protein BclA of Bacillus anthracis Is Effective as a Booster for Mice Primed with Suboptimal Amounts of Protective AntigenInfection and Immunity, 2007
- Identification of In Vivo-Expressed Immunogenic Proteins by Serological Proteome Analysis of the Bacillus anthracis SecretomeInfection and Immunity, 2007
- Bacillus anthracis secretome time course under host-simulated conditions and identification of immunogenic proteinsProteome Science, 2007
- Proteomic Profiling and Identification of Immunodominant Spore Antigens of Bacillus anthracis , Bacillus cereus , and Bacillus thuringiensisApplied and Environmental Microbiology, 2006
- Search for Bacillus anthracis Potential Vaccine Candidates by a Functional Genomic-Serologic ScreenInfection and Immunity, 2006
- Differential Proteomic Analysis of theBacillus anthracisSecretome: Distinct Plasmid and Chromosome CO2-Dependent Cross Talk Mechanisms Modulate Extracellular Proteolytic ActivitiesJournal of Bacteriology, 2006