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.