Scientific Publications by FDA Staff

Vaccine 2018 Oct 15;36(43):6379-82

Improving the Stability of Recombinant Anthrax Protective Antigen Vaccine.

Verma A, Burns DL

Development of recombinant protective antigen (rPA)-based anthrax vaccines has been hindered by a lack of stability of the vaccines associated with spontaneous deamidation of asparagine (Asn) residues of the rPA antigen during storage. In this study, we explored the role that two deamidation-prone Asn residues of PA, Asn713 and Asn719, play in the stability of rPA-based anthrax vaccines. We modified both of these residues to glutamine (Gln) and generated rPA(N713Q/N719Q), since Gln would not be expected to deamidate on a time scale relevant to vaccine storage. We focused on these two residues because Asn713 and Asn719 are located directly adjacent to the receptor binding site of PA and we recently found that the receptor-binding capacity of PA enhances its immunogenicity. While wild-type rPA vaccine formulated with aluminum hydroxide lost immunogenicity upon storage, as measured by induction of toxin-neutralizing antibodies in mice, the rPA(N713Q/N719Q) vaccine did not exhibit a significant loss in immunogenicity. This finding suggests that modification of Asn713 and Asn719 of rPA to deamidation-resistant amino acids may improve the stability of rPA-based anthrax vaccines.