Mechanism of Action

Live attenuated spore vaccines. Live spore vaccines used in veterinary practice, as well as the Soviet Sterne live spore vaccine used in humans, are (pX01+, pX02−) unencapsulated strains of B. anthracis. These vaccines are administered intramuscularly, subcutaneously, or by scarification. The host mounts an immune response to the organism and its toxin proteins. Live spore vaccines induce a humoral immune response. However, the live spore vaccine also elicits a cell-mediated immune response (Shlyakhov and Rubinstein, 1994b). The absence of the capsule reduces the virulence of the organism, yet the bacillus can still produce the toxin proteins PA, EF, and LF. Thus, the formation of active edema toxin and lethal toxin is possible.

Protective antigen vaccines. The U.K. and U.S. vaccines for humans are alum-precipitated cell-free filtrates of Bacillus anthracis. In the case of the U.S. vaccine, this precipitate is adsorbed onto aluminum hydroxide. The aluminum hydroxide adjuvant is included in the vaccine preparation to boost the immune response to the PA. Aluminum hydroxide is used in many vaccines and is thought to stimulate humoral rather than cell-mediated immunity (Ivins et al., 1998). The culture filtrates are processed to maximize the content of PA. The cell-free filtrate is primarily PA but also contains EF, LF, and other contaminants from culture (Ivins et al., 1998; Miller et al., 1998). PA vaccine for humans also elicited antibody production to EF and LF in rats and guinea pigs (Ivins et al., 1986; Turnbull et al., 1986; Ivins, 1988), suggesting that the contamination is sufficient to elicit a biological response.

The primary goal of anthrax vaccination is to produce neutralizing antibodies to PA. Subsequent exposure to anthrax infection would then eliminate the pathogenic potential of B. anthracis by eliciting the production of antibodies that neutralize PA. Without PA, EF and LF are incapable of acting as virulence factors. Barnard and Friedlander (1999) vaccinated guinea pigs with several different live recombinant Bacillus anthracis strains (pX01−, pX02−) that each produced a different amount of PA without producing the capsule, EF, or LF. The protective effect of these strains correlated with the production of PA and with the anti-PA antibody titer elicited in vivo. Studies by Turnbull and colleagues (1988) and Ivins (1988) in guinea pigs have provided evidence that PA is an essential component of the vaccine and that protection against anthrax in guinea pigs is possible in the absence of any detectable antibody to LF or EF. However, some studies have suggested that the protective effect of anthrax vaccine does not necessarily correlate with the antibody titer to PA in vivo. Studies by Little and Knudson (1986) indicated that a high titer to PA did not necessarily reflect the level of expected protection from infection. Studies by Turnbull and colleagues (1988) suggested that it is also important for the PA antigen to be presented to the immune system in such a way as to stimulate more than just a humoral immune response. Challenge tests with aerosol anthrax spores have shown that the Sterne live spore vaccine was more efficacious than PA-based

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