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

Antonio Nakouzi,Johanna Rivera,Arturo Casadevall,Richard F Rest

doi:10.1186/1471-2180-8-159

Antonio Nakouzi, Johanna Rivera + Show 2 more

Open Access

https://doi.org/10.1186/1471-2180-8-159

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Abstract

BackgroundBacillus anthracis has 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 for B. anthracis but subsequent studies have questioned its relevance in pathogenesis. In this study, we examined the immunogenicity of recombinant anthrolysin O (rALO) in mice.ResultsBALB/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. anthracis Sterne 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.ConclusionOur results suggest that ALO contributes to the virulence of B. anthracis Sterne strain in this infection model and that Ab response to ALO may contribute to protection in certain circumstances.

Highlights

Bacillus anthracis has two major virulence factors: a tripartite toxin that produces lethal and edema toxins and a polyglutamic acid capsule
In vitro neutralizing activity Given that anthrolysin O (ALO) is cytotoxic in vitro, we examined whether the various anti-recombinant anthrolysin O (rALO) monoclonal antibodies (mAbs) could reduce killing of macrophages by rALO in vitro
We have revisited the role of ALO in B. anthracis pathogenesis by making mAbs to rALO and assessing their ability to modify the course of lethal infection in mice

Summary

Introduction

Bacillus anthracis has 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 for B. anthracis but subsequent studies have questioned its relevance in pathogenesis. A comparison of ALO-deficient and wildtype strains in an inhalation anthrax model revealed no difference in virulence, suggesting that this toxin was not essential for virulence [4]. Consistent with this observation, immunization with ALO protects mice against the toxin but not infection with B. anthracis [5]. The current view is that ALO is a potent cytotoxin in vitro that has not been demonstrated to have a significant role in virulence

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