Effect of adjuvants and route of immunizations on the immune response to recombinant plague antigens.

In this study, we compare four different adjuvants, LT(R192G), CpG ODN, MPL((R))TDM, and alum, for their ability to affect the magnitude, distribution, and duration of antibody responses against F1-V, the lead-candidate antigen for the next generation vaccine against plague, in a murine model. In addition, three different routes of immunization-intranasal (IN), transcutaneous (TC), and subcutaneous (SC) were compared with each adjuvant. Since aerosol exposure to biological warfare agents is of primary concern, both serum and bronchioalveolar lavage (BAL) were analyzed for antigen-specific antibody responses. The most significant findings of the study reported here are that (1) the adjuvant influences the Type 1/Type 2 balance of the antibody response in both the serum and BAL, (2) mucosal immunization is not necessary to obtain F1-V-specific BAL responses, (3) non-traditional adjuvants such as LT(R192G) work when delivered subcutaneously, (4) the route of immunization affects the magnitude of the immune response, and (5) F1-V is highly immunogenic by some routes even in the absence of an exogenously applied adjuvant. These studies provide important insights into the influence of different classes of adjuvants on the immune outcome in biodefense vaccines and for development of new-generation vaccines against other pathogens as well.