A dually active anthrax vaccine that confers protection against both bacilli and toxins
- Gi-Eun Rhie†,‡,
- Michael H. Roehrl§,
- Michael Mourez†,
- R. John Collier†,
- John J. Mekalanos†, and
- Julia Y. Wang¶,∥
- Departments of †Microbiology and Molecular Genetics and §Biological Chemistry and Molecular Pharmacology, and ¶Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
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Contributed by John J. Mekalanos, July 17, 2003
Abstract
Systemic anthrax is caused by unimpeded bacillar replication and toxin secretion. We developed a dually active anthrax vaccine (DAAV) that confers simultaneous protection against both bacilli and toxins. DAAV was constructed by conjugating capsular poly-γ-d-glutamic acid (PGA) to protective antigen (PA), converting the weakly immunogenic PGA to a potent immunogen, and synergistically enhancing the humoral response to PA. PGA-specific antibodies bound to encapsulated bacilli and promoted the killing of bacilli by complement. PA-specific antibodies neutralized toxin activity and protected immunized mice against lethal challenge with anthrax toxin. Thus, DAAV combines both antibacterial and antitoxic components in a single vaccine against anthrax. DAAV introduces a vaccine design that may be widely applicable against infectious diseases and provides additional tools in medicine and biodefense.
Footnotes
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↵ ∥ To whom correspondence should be addressed. E-mail: julia_wang{at}rics.bwh.harvard.edu.
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↵ ‡ On leave within the International Postdoctoral Program of the International Vaccine Institute, Seoul 151-600, Korea.
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Abbreviations: DAAV, dually active anthrax vaccine; DTA, diphtheria toxin A chain; LF, lethal factor; LFN, PA-binding domain of LF; PA, protective antigen; PGA, poly-γ-d-glutamic acid.
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Note Added in Proof. During the review of this paper, a publication by Schneerson et al. (25) came to our attention that reports the synthesis of PGA–PA conjugates by using different chemical methods. The findings thus confirm independently the two groups' common conclusions concerning the utility of such conjugates as vaccines that dramatically improve the immunogenicity of PGA.
- Copyright © 2003, The National Academy of Sciences
