Lethally-irradiated Yersinia pestis immunization protects against the plague: a novel vaccine candidate (47.23)

Abstract

Abstract We provide evidence here that immunization with lethally γ-irradiated Yersinia pestis provides an effective and novel vaccine against the plague. Traditionally, neither chemical nor heat killing of bacteria has been successful in inducing an appropriate immune response to provide protection against further infection. It has been postulated, however, that inactivation via γ-irradiation would allow for retention of both adjuvant and antigenic components necessary for an effective vaccine. We hypothesize that, unlike many vaccines that induce predominately an antibody response, γ-irradiated whole bacteria will result in both a protective humoral and cellular immune response. Recent evidence that γ-irradiated Listeria monocytogenes protected mice from future exposure to L. monocytogenes supports this hypothesis. Y. pestis, the cause of the plague, is endemic in much of the world. It creates a considerable health risk and is now also considered a putative agent for bioterrorism, although current vaccine candidates have potential pitfalls. Immunization with lethally γ-irradiated Y. pestis (600 kRads from a 137Ce source) provides significant protection against the plague in the absence of any additional stimulatory adjuvant in both inbred B10.T(6R) mice and out-bred Swiss Webster mice, LD50’s of greater than 106 CFUs in both strains, compared to 103 CFUs and 20 CFUs in sham immunized B10.T(6R) and Swiss Webster mice respectively. These data suggest both a new and effective vaccine for Y. pestis, as well as potential vaccines that have remained elusive for other bacteria.