Passive administration of monoclonal antibodies to anthrolysin O prolong survival in mice lethally infected with Bacillus anthracis.
BACKGROUND
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 dependent 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.


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. 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.


CONCLUSIONS
Our 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.
Nakouzi
Antonio
A
Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA. nakouzi@aecom.yu.edu
Rivera
Johanna
J
Rest
Richard F
RF
Casadevall
Arturo
A
D000818:Animals; D000881:Anthrax / Q000276:immunology* / Q000382:microbiology; D022122:Anthrax Vaccines / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology*; D001408:Bacillus anthracis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D005260:Female; D007116:Immunization, Passive; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000276:immunology; D016019:Survival Analysis
D022122:Anthrax Vaccines; D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C498000:anthrolysin O, Bacillus anthracis