Anthrax antigen Other names: Bacillus anthracis antigen Anthrax vaccine

Anthrax is a zoonotic disease caused by the Gram-positive, spore-forming bacterium Bacillus anthracis. Anthrax antigen induces antibodies raised against PA that may contribute to protection by neutralizing the activities of the cytotoxic lethal toxin and edema toxin of Bacillus anthracis³. Bacillus anthracis proteins other than PA may be present in anthrax antigen, but their contribution to protection has not been determined.

Since it is not feasible or ethical to conduct controlled clinical trials with anthrax, the efficacy of anthrax antigen in a post-exposure setting is based on studies in animals. Pre-exposure prophylaxis animal models were used to derive protective antibody thresholds to bridge animal efficacy and human immunogenicity data and predict efficacy in humans.

Pivotal efficacy animal studies were conducted in rabbits and nonhuman primates (NHPs). Animals received two IM vaccinations four weeks apart with serial dilutions of anthrax antigen and were subjected to lethal challenge on study day 70 with aerosolized B. anthracis spores at a target dose exceeding the 50% lethal dose by 200-fold. Serum samples were collected at various time points prior to challenge for immune response analysis via anthrax lethal toxin neutralizing antibody (TNA) assay. The relationship between pre-challenge serum TNA levels and survival was evaluated. Logistic regression analysis demonstrated that a 70% probability of survival was associated with a TNA NF₅₀ (50% neutralization factor) level of 0.56 in rabbits and 0.29 in NHPs.

The ability of anthrax antigen to increase survival after the cessation of the post-exposure antimicrobial treatment, as compared with antimicrobial treatment alone, was investigated in two post-exposure animal model studies. In these studies, rabbits were challenged via inhalation with aerosolized B. anthracis spores and subsequently treated with levofloxacin administered via oral gavage once daily for 7 days starting at 6-12 hours post-exposure, with or without two intramuscular injections of anthrax antigen one week apart. Survival among animals that received both antimicrobial treatment and vaccination was between 70-100% and increased in a vaccine dose-dependent manner. In contrast, only 44% and 23% survival was observed among animals that received antimicrobial treatment only in the first and the second study, respectively (p <0.0006 and p <0.004, respectively).