Scientific Publications by FDA Staff

Clin Vaccine Immunol 2010 Sep;17(9):1390-7

Analysis of antibody responses to protective antigen-based anthrax vaccines through use of competitive assays.

Brady RA, Verma A, Meade BD, Burns DL

The licensed anthrax vaccine and many of the new anthrax vaccines being developed are based on protective antigen (PA), a non-toxic component of anthrax toxin. For this reason, an understanding of the immune response to PA vaccination is important. In this study, we examined the antibody response elicited by PA-based vaccines and identified the domains of PA that contribute to that response in humans as well as non-human primates (NHPs) and rabbits, animal species that will be used to generate efficacy data to support approval of new anthrax vaccines. To this end, we developed a competitive ELISA assay using purified, recombinant forms of intact PA and its individual domains. We found that PA-based vaccines elicited IgG antibodies to each of the four PA domains in all three species. We also developed a competitive toxin neutralization assay, which showed that rabbits, NHPs, and humans all have functional antibody populations that bind to domains 1, 3, and 4. While the domain specificity of the antibody response elicited by PA-based vaccines was similar in humans, NHPs and rabbits, competitive assays suggested that humans may have a more significant secondary population of IgG antibodies that bind to partially unfolded or incorrectly folded PA. These findings provide information that will be useful when linking animal protection data to humans via an antibody bridge to establish efficacy of new anthrax vaccines.