The search for a new-generation human anthrax vaccine
Abstract : Anthrax is a disease primarily of herbivores, but humans can become infected through contact with infected animals or animal products. The etiological agent, Bacillus anthracis, possesses two primary virulence factors: a poly-D-glumatic acid capsule and an exotoxic mixture of three proteins: protective antigen (PA), edema factor (EF), and lethal factor (LF). None of the three proteins individually possesses demonstrable toxic activity; however, intravenous injection of PA + LF kills mice, rats, and guinea pigs, whereas intradermal injection of PA + EF produces edematous lesions in the skin of guinea pigs and rabbits. The combination of PA + LF is termed lethal toxin, whereas PA + EF is referred to as edema-producing toxin. The conventional designation for mixtures of all three components is anthrax toxin. The genes encoding PA, EF, and LF are located on a 174-kilobase (kb) plasmid, pXO1; the genes responsible for capsule synthesis are on a 91 kb plasmid, pXO2. In the United States, the currently licensed human vaccine against anthrax (designated here as MDPH-PA) consists of aluminum hydroxide-absorbed, supernatant material, primarily PA (11), from fermenter cultures of another toxinogenic, nonencapsulated strain, V770-Np1-R. Immunization with MDPH-PA requires a series of six doses within 18 mo, followed by yearly boosters. Immunization occasionally results in local pain and inflammation, and there is some evidence indicating that MDPH-PA may have diminished efficacy against certain virulent strains of B. The need for an improved human vaccine against anthrax is apparent.