Plague vaccine: Homologous and heterologous prime-boost strategies using recombinant Yersinia pestis proteins.

摘要

Yersinia pestis has been identified as a potential agent of biological warfare or bioterrorism and presents a particular challenge to vaccine developers because of the severity and potential transmissibility of the pneumonic form of the disease in humans. A Y. pestis-derived fusion protein (F1-V) has shown great promise as a protective antigen in murine studies. Here, initial studies were done to examine the ability of different prime-boost regimens, including parenteral, mucosal, and transcutaneous delivery, to induce a specific immune response of high titer and long duration. Next, we examine different prime-boost regimens in order to determine if heterologous boosting can provide protection against aerosol challenge when compared to homologous boosting. Additionally, we examine whether non-parenteral immunization can prime for a parenteral boost. Finally, we examine the role of the adjuvant in inducing a protective immune response. The most significant findings of the studies reported here are that (1) heterologous boosting can be as or more effective than homologous boosting for induction of either serum or BAL anti-F1-V IgG1 responses, (2) heterologous boosting protects mice as well as homologous boosting against aerosol challenge with Y. pestis , (3) parenteral immunization is not required to protect mice against aerosolized plague challenge, (4) the route of immunization and choice of adjuvant influence the magnitude of the antibody response as well as the IgG1/IgG2a ratio, and (5) inclusion of an appropriate adjuvant is critical for non-parenteral immunization.