A dually active anthrax vaccine that confers protection against both bacilli and toxins.
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-gamma-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.
Rhie
Gi-Eun
GE
Department of Microbiology and Molecular Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Roehrl
Michael H
MH
Mourez
Michael
M
Collier
R John
RJ
Mekalanos
John J
JJ
Wang
Julia Y
JY
D000818:Animals; D022122:Anthrax Vaccines / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D016253:Microscopy, Immunoelectron
D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D003165:Complement System Proteins