>>Published online before print September 5, 2003
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.1834478100
Immunology
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
Contributed by John J. Mekalanos, July 17, 2003
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--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.<<
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