The specific aim is to develop novel strategies to improve the immunogenicity of vaccines targeting bioterror pathogens, focusing on AVA (anthrax vaccine adsorbed) and recombinant protective antigen (rPA) as the potential candidates.
The intent is to examine the use of a toll like receptor 9 (TLR9) ligand (a synthetic oligodeoxynucleotide expressing CpG motifs (CpG ODN)) in three settings:
i) As a stand-alone agents to improve the host's capacity to resist infection by anthrax, ii) As a vaccine adjuvant, accelerating and magnifying the anti-PA antibody response elicited by a co-administered AVA and recombinant protective antigen (rPA) vaccines, and
iii) As an adjuvant in combination with AVA or rPA delivered by novel means (by sterically stabilized cationic liposomes) to boost anti-PA or immunoprotective immunity.
Finally, by incorporating other TLR ligands (such as dsRNA, MALP-2, PAMCys3, and loxoribine, ligands for TLR3, TLR2/6, TLR2, and TLR7/8 respectively) in the final formulation we plan to augment the adjuvant effect mediated by CpG ODN, thereby improving protective performance of the vaccine. Studies planned for this proposal will examine whether the addition of CpG ODN to the AVA (or rPA antigen) vaccine 1) elicits a more rapid protective immune response than AVA alone and 2) will have an antigen sparing effect, allowing the use of less AVA and thus decreasing the reactogenicity associated with AVA vaccination.
We also plan to investigate the use of CpG ODN and AVA complexed to be co-encapsulated in liposomes (which improve the targeting and subsequent simultaneous presentation of the vaccine and adjuvant to antigen presenting cells, thus improving uptake and immunogenicity). Results from these studies should have considerable applicability to other vaccines targeting new emerging infectious or bio-threat agents.
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