Passive administration of monoclonal antibodies to Anthrolysin O prolong survival in mice lethally infected with Bacillus anthracis

Abstract

Background: Bacillus anthracishas two major virulence factors: a tripartite toxin that produces lethal and edema toxins and a polyglutamic acid capsule. A recent report suggested that a toxin belonging to the cholesterol dependant cytolysin (CDC) family, anthrolysin O (ALO) was a new virulence factor forB. anthracisbut subsequent studies have questioned its relevance in pathogenesis. In this study, we examined the immunogenicity of recombinant anthrolysin O (rALO) in mice.Results: BALB/c mice immunized with rALO and boosted after two weeks, produce sera with strong Ab responses with a predominance of IgG1 and IgG2a. Five hybridomas to rALO were recovered representing the IgM, IgG1, and IgG2b isotypes. Passive administration of 3 of the five monoclonal antibodies (mAbs) to rALO prior to infection with lethal intravenous (i.v.)B. anthracisSterne strain infection in mice was associated with enhanced average survival and a greater likelihood of surviving infection. A combination of two mAbs to ALO was more effective than either mAb separately. One mAb (64F8) slowed the toxicity of rALO for J774.16 macrophage-like cells.Conclusion: Our results suggest that ALO contributes to the virulence ofB. anthracisSterne strain in this infection model and that Ab response to ALO may contribute to protection in certain circumstances.