Comparative safety and efficacy against Bacillus anthracis of protective antigen and live vaccines in mice

The efficacy and mechanisms of protection of two live vaccines and of a protective antigen (PA) vaccine against Bacillus anthracis were studied in inbred mice. Mice that differed in their natural resistance to killing by Sterne, a non-encapsulated, toxigenic vaccine strain of B. anthracis, were used. Vaccination with live Sterne spores protected Sterne-resistant mice against challenge with the virulent Vollum 1B (V1B) strain of B. anthracis, but only at doses of Sterne greater than or equal to 0.1 50% lethal dose. The live B. subtilis recombinant strain PA2, which produces the PA component of anthrax toxin, fully protected (CBA/J) or partially protected (BALB/cJ) Sterne-resistant mice against V1B. Neither immunization with the cell-free PA vaccine nor passive administration of anti-PA antiserum protected Sterne-resistant mice against V1B. Sterne-susceptible A/J mice were not protected against V1B by either live vaccine or by the PA vaccine. However, immunization with strain PA2 induced anti-PA antibody and protected A/J mice against Sterne. A/J mice passively treated with antitoxin antibodies also survived Sterne, and survivors were then partially protected against V1B. Thus, immunity to Sterne correlated with an effective anti-PA response. Immunity to fully virulent V1B also required PA but may involve mechanisms in addition to humoral immunity.