Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 202, Issue 2, Pages 251-260Publisher
OXFORD UNIV PRESS INC
DOI: 10.1086/653495
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Funding
- National Institute of Allergy and Infectious Diseases [U19AI062629]
- National Center for Research Resources [P20RR15577]
- Walter Reed Army Medical Center Vaccine Healthcare Centers Network and Allergy-Immunology Department
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Bacillus anthracis remains a serious bioterrorism concern, and the currently licensed vaccine remains an incomplete solution for population protection from inhalation anthrax and has been associated with concerns regarding efficacy and safety. Thus, understanding how to generate long-lasting protective immunity with reduced immunizations or provide protection through postexposure immunotherapeutics are long-sought goals. Through evaluation of a large military cohort, we characterized the levels of antibodies against protective antigen and found that over half of anthrax vaccinees had low serum levels of in vitro toxin neutralization capacity. Using solid-phase epitope mapping and confirmatory assays, we identified several neutralization-associated humoral epitopes and demonstrated that select antipeptide responses mediated protection in vitro. Finally, passively transferred antibodies specific for select epitopes provided protection in an in vivo lethal toxin mouse model. Identification of these antigenic regions has important implications for vaccine design and the development of directed immunotherapeutics.
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