An ideal vaccine against potential agents of biological warfare/bioterrorism should be safe, easy to deliver, provide long-lasting protection, require only one or a few doses, and provide protective immunity against different agents. Moreover, since mucosal and respiratory surfaces represent the first productive points of contact with the human host for many aerosolized biological agents, the role of mucosal immunity in protection needs to be examined. Nonparenteral delivery of vaccines (i.e., by the mucosal or transcutaneous route) has been shown to be effective at inducing both humoral and cellular antigen-specific immune responses in both the systemic and mucosal compartments of immunized animals and humans. Such """"""""needle free"""""""" immunizations offer many potential advantages over parenteral immunization and are being evaluated by a number of groups for use in biodefense vaccines. Induction of immune responses by these nonparenteral routes is dependent upon the co-administration of appropriate adjuvants that can initiate and support the transition from innate to adaptive immunity. In this application we are proposing to investigate three novel adjuvants (LTR192G), CpG ODN, CTA1-DD) for their ability to induce high titer, long lived, protective antibody responses against relevant vaccine antigens from B. anthracis (rPA), Y. pestis (F1-V), botulinum toxin (Hc), and staphylococcal enterotoxin B (SEBv). The findings from these studies should be broadly applicable to other antigens from these and other biological agents. The primary objective of these studies is the optimization and preclinical testing of these novel adjuvants, each of which has previously shown promise in other infectious disease vaccines delivered mucosally or transcutaneously. It is expected that one or more of these adjuvants will be considered as candidates for future Phase I-II-III testing in clinical trial programs. Another objective of this application is to determine if nonparenteral boosting can induce a protective secondary immune response in animals that have been parenterally primed and if that response can be redirected to include a mucosal immune component. Challenge studies will allow us to correlate immune responses with protective efficacy and determine the contribution of mucosal immune responses to protection. Finally, we will determine the effectiveness of a combined vaccine consisting of relevant antigens from the four different pathogens with the specific objective of determining synergy or interference between the vaccine components and the role of adjuvants and route of delivery in overcoming interference.
| Uddowla, Sabena; Freytag, Lucy C; Clements, John D (2007) Effect of adjuvants and route of immunizations on the immune response to recombinant plague antigens. Vaccine 25:7984-93 |
