Recombinant Exosporium Protein BclA of Bacillus anthracis Is Effective as a Booster for Mice Primed with Suboptimal Amounts of Protective Antigen
- 1 November 2007
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 75 (11), 5240-5247
- https://doi.org/10.1128/iai.00884-07
Abstract
Bacillus collagen-like protein of anthracis (BclA) is an immunodominant glycoprotein located on the exosporium of Bacillus anthracis . We hypothesized that antibodies to this spore surface antigen are largely responsible for the augmented immunity to anthrax that has been reported for animals vaccinated with inactivated spores and protective antigen (PA) compared to vaccination with PA alone. To test this theory, we first evaluated the capacity of recombinant, histidine-tagged, nonglycosylated BclA (rBclA) given with adjuvant to protect A/J mice against 10 times the 50% lethal dose of Sterne strain spores introduced subcutaneously. Although the animals elicited anti-rBclA antibodies and showed a slight but statistically significant prolongation in the mean time to death (MTD), none of the mice survived. Similarly, rabbit anti-rBclA immunoglobulin G (IgG) administered intraperitoneally to mice before spore inoculation increased the MTD statistically significantly but afforded protection to only 1 of 10 animals. However, all mice that received suboptimal amounts of recombinant PA and that then received rBclA 2 weeks later survived spore challenge. Additionally, anti-rBclA IgG, compared to anti-PA IgG, promoted a sevenfold-greater uptake of opsonized spores by mouse macrophages and markedly decreased intramacrophage spore germination. Since BclA has some sequence similarity to human collagen, we also tested the extent of binding of anti-rBclA antibodies to human collagen types I, III, and V and found no discernible cross-reactivity. Taken together, these results support the concept of rBclA as being a safe and effective boost for a PA-primed individual against anthrax and further suggest that such rBclA-enhanced protection occurs by the induction of spore-opsonizing and germination-inhibiting antibodies.Keywords
This publication has 33 references indexed in Scilit:
- Bacillus anthracis Exosporium Protein BclA Affects Spore Germination, Interaction with Extracellular Matrix Proteins, and HydrophobicityInfection and Immunity, 2007
- Protective Role of Bacillus anthracis Exosporium in Macrophage-Mediated Killing by Nitric OxideInfection and Immunity, 2007
- The US Capitol Bioterrorism Anthrax Exposures: Clinical Epidemiological and Immunological CharacteristicsThe Journal of Infectious Diseases, 2007
- Significant passive protective effect against anthrax by antibody to Bacillus anthracis inactivated spores that lack two virulence plasmidsMicrobiology, 2006
- DNA vaccination against anthrax in mice—combination of anti-spore and anti-toxin componentsVaccine, 2006
- Patterns of antibody response in humans to the anthrax vaccine adsorbed (AVA) primary (six-dose) seriesVaccine, 2006
- Importance of Nitric Oxide Synthase in the Control of Infection by Bacillus anthracisInfection and Immunity, 2006
- AnthraxAnnual Review of Microbiology, 2001
- AnthraxNew England Journal of Medicine, 1999
- Germination of Bacillus anthracis spores within alveolar macrophagesMolecular Microbiology, 1999