Alternative Approach to Combination Vaccines: Intradermal Administration of Isolated Components for Control of Anthrax, Botulism, Plague and Staphylococcal Toxic Shock

摘要

As the number of investigational and approved vaccines continues to increase, the frequency of vaccinations will soon reach a practical limit. Though combination vaccines ultimately lead to a reduction in the required number of vaccinations, incompatibilities between individual components often limit development of these mixtures. Our results suggest the feasibility of protective vaccination against multiple diseases by intradermal administration of each antigen to physically isolated sites, thus avoiding potentially incompatible vaccine mixtures. Intradermally administered arrays of vaccines for protection from anthrax, botulism, plague, and staphylococcal toxic shock were biocompatible in vivo, retained potent antibody responses, and were well tolerated by rhesus macaques. Vaccinated primates were completely protected from lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B, and partially protected against challenge by Yersinia pestis. In addition to demonstrating a practical alternative to vaccine mixtures, our results indicated no biological limitation to the number of vaccines administered.