Multiple antigenic peptide vaccine targeting the loop neutralizing determinant of protective antigen from Bacillus anthracis completely protects rabbits from aerosol spore challenge (52.24)

Abstract

Abstract The loop neutralizing determinant (LND) from domain 2 of Bacillus anthracis protective antigen (PA) has been shown to represent a potentially important target for an epitope-specific vaccine for anthrax. This region in the 2β2-2β3 loop of PA is immunologically inert, since rabbits immunized with PA or otherwise immune to PA do not contain antibody specific for this region. Herein we evaluated the immunogenicity in rabbits of a MAP peptide comprising the T* helper T cell epitope from Plasmodium falciparum colinearly synthesized at either the N- or C-terminus with a.a. 304-319 from PA. In initial studies, the MAP peptides formulated in Freund’s adjuvant were found to be highly immunogenic in rabbits, rapidly eliciting high levels of neutralizing antibody. To more fully evaluate this peptide as an anthrax vaccine, we immunized separate groups of rabbits (n=7) five times at two-week intervals with either of the two LND MAP peptides or with soluble PA in Freund’s adjuvant and then subjected all rabbits to a 200 LD50 aerosol spore challenge with B. anthracis Ames strain. 100% of rabbits immunized with the LND MAP in the B-T orientation and with soluble PA, and 89% of rabbits immunized with the LND MAP in the T-B orientation, survived the spore challenge, while all naïve rabbits died. Analysis of post-challenge serum suggested little or no spore germination in challenged rabbits. We conclude that the LND MAP peptide is a promising epitope-specific prototype vaccine for anthrax.