The length of the dosage schedule, along with questions about the extent of the efficacy of the current vaccine against newly engineered strains of anthrax, has led to ongoing research efforts to produce a second-generation recombinant vaccine (Ibrahim et al., 1999; Nass, 1999). Additionally, researchers hope that new processes will be designed to ensure a more precise amount and a more highly purified component of protective antigen in the vaccine (GAO, 1999b; Russell, 1999).


Anthrax disease results from exposure to the bacterium Bacillus anthracis through three primary routes: cutaneous, inhalation, and gastrointestinal. Regardless of the route of exposure, the presence of the organism provokes an immune response. Both humoral and cell-mediated immunity play a role in defending against B. anthracis (Turnbull et al., 1986; Shlyakhov and Rubinstein, 1994b). An individual who has recovered from B. anthracis infection is protected against a subsequent infection with the same organism. Some studies have correlated protective immunity in animals with the antibody response to B. anthracis (Barnard and Friedlander, 1999), but other studies have not confirmed this finding (Little and Knudson, 1986; Turnbull et al., 1986).

Knowledge of the pathogenic mechanisms of Bacillus anthracis can provide insight into the potential adverse effects associated with administration of the various anthrax vaccines (Friedlander, 1997; Ibrahim et al., 1999). B. anthracis is pathogenic by virtue of its capsule and protein exotoxins. The capsule of the bacillus is encoded by an extrachromosomal plasmid pX02 (Little and Knudson, 1986). Another plasmid (pX01) encodes for all three toxin proteins: edema factor (EF), lethal factor (LF), and protective antigen (PA). PA, the transport protein, is required for transport of the enzymatic proteins EF and LF into the target cells of the host; PA must be present for the toxins to confer virulence (Ibrahim et al., 1999). In vitro studies of the toxins have revealed that PA binds to cells and undergoes limited proteolysis, which exposes a potential binding site for LF and EF. The LF–PA and EF–PA complexes enter the target cell by receptor-mediated endocytosis, followed by translocation of LF or EF to the cytosol (Friedlander, 1986; Leppla et al., 1990). The edema toxin complex, composed of EF and PA, acts through calmodulin-dependent adenylate cyclase activity to cause the excessive fluid accumulation that is associated with anthrax infection (Leppla, 1982; Ibrahim et al., 1999). The lethal toxin complex, composed of LF and PA, is the primary cause of shock and death (Ibrahim et al., 1999). Lethal toxin is a zinc metallopeptidase that is rapidly cytolytic for macrophages in vitro and induces the release of the cytokine tumor necrosis factor (TNF) from macrophages (Hanna et al., 1993). Studies in mice indicate that TNF and interleukin-1, in particular, contribute to the death induced by injection of lethal toxin (Friedlander, 1986).

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