Immune correlates of protection against anthrax

Bacillus anthracis protective antigen (PA) has been produced from a recombinant B. subtilis and its efficacy, when combined with the Ribi adjuvant (MPL-TDW-CWS) or alhydrogel, has been compared with that of the licensed UK human vaccine, in guinea pigs challenged with aerosolized Ames strain spores. Recombinant PA combined with the Ribi adjuvant performed as well as PA from B. anthracis cultures in previous reports (Ivins & Welkos 1986; Ivins et al. 1990; Turnbull et al. 1991; Jones et al. 1996; McBride et al. 1998) giving protection in 100% of animals exposed to the highest challenge dose of the Ames strain of B. anthracis that can be administered practically (retained lung doses of approximately 106 spores). In attempts at identifying markers of protection in immunized individuals, rPA in combination with the Ribi adjuvant induced a marker IgG2 response in guinea pigs with no significant differences in IgG1 levels when compared with other vaccine formulations (McBride et al. 1998). In BALBc mice, rPA with the Ribi adjuvant induced a higher IgG2a response compared with rPA with anhydrogel and the human vaccine. To examine the role of anti-PA-specific antibodies in protection, guinea pig sera is being passively transferred into guinea pigs and SCID mice, followed by protection. Similarly, B- and T-lymphocytes from immunized BALB/c mice are being separately and passively transferred into SCID mice with subsequent challenge. The neutralizing ability of the PA-specific antibodies is being studied using an in vitro macrophage lysis assay.