Neutralizing Antibodies and Persistence of Immunity following Anthrax Vaccination

Abstract

Anthrax toxin consists of protective antigen (PA) and two toxic components, lethal factor (LF) and edema factor (EF). PA binds to mammalian cellular receptors and delivers the toxic components to the cytoplasm. PA is the primary antigenic component of the current anthrax vaccine. Immunity is due to the generation of antibodies that prevent the PA-mediated internalization of LF and EF. In this study, we characterized sera obtained from vaccinated military personnel. Anthrax vaccine is administered in a series of six injections at 0, 2, and 4 weeks and 6, 12, and 18 months, followed by annual boosters. The vaccination histories of the subjects were highly varied; many subjects had not completed the entire series, and several had not received annual boosters. We developed a simple colorimetric assay using alamarBlue dye to assess the antibody-mediated neutralization of LF-mediated toxicity to the J774A.1 murine macrophage cell line. Recently vaccinated individuals had high antibody levels and neutralizing activity. One individual who had not been boosted for 5 years had low immunoglobulin G antibody levels but a detectable neutralization activity, suggesting that this individual produced low levels of very active antibodies.

Serum IgG antibody response to the protective antigen (PA) of Bacillus anthracis induced by anthrax vaccine adsorbed (AVA) among U.S. military personnel

“…With the increase in GM antibody levels the additional seroconversion rate decreased. Although none of the study subjects had anthrax or a history of receiving an anthrax vaccine all had low but detectable levels of anti-PA IgG prior to vaccination with AVA, confirming previous reports [18]. These antibodies were likely induced by cross-reactive antigens of non-anthrax bacilli or non-pathogenic Clostridia [19][20][21].…”

Immunogenicity of Bacillus anthracis Protective Antigen Domains and Efficacy of Elicited Antibody Responses Depend on Host Genetic Background

“…Although the immunological mechanisms responsible for the differences in antigenicity among the mouse strains were not investigated, we surmised that this phenomenon might be a reflection of differences in the processing and presentation of these antigens in genetically different mice. This finding echoes the observation that there is great heterogeneity in the human individual response to PA immunization with respect to the titer elicited and the neutralizing activity of the immune serum (13).…”

Synthetic Peptide Vaccine Targeting a Cryptic Neutralizing Epitope in Domain 2 ofBacillus anthracisProtective Antigen

“…The LND neutralizing specificity targets the 2␤2-2␤3 loop region, which is critical for LeTx function, and the primacy of the loop sequences in enabling LeTx cytotoxicity might hinder or even preclude the malicious reengineering of PA to evade the LND specificity. Other potential applications for a totally synthetic, epitope-specific anthrax vaccine targeting the LND might be for use in individuals who respond poorly to vaccination with PA-based vaccines and possibly in postexposure scenarios, where a role for vaccination is being studied, but where a reluctance to give vaccines containing whole PA might be warranted (6,18).…”