This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The TLR9 ligand CpG C ISS-ODN, C274, effectively activates macaque plasmacytoid DCs and B cells, providing the rationale for testing C274 as an adjuvant for anti-HIV vaccine strategies. We are also pursuing the possibility that the TLR3 ligand polyIC, which activates myeloid DCs and epithelial cells, could be employed to boost innate and adaptive responses to augment vaccine efficacy. Expanding our initial observations that in vivo application of C274 on macaque tonsillar tissue leads to the activation tonsillar DCs, particularly the plasmacytoid DC subset, we have tested the responses to tonsillar application of polyIC. In vivo polyIC application boosted immune local immune responses, as detected by the release of cytokines/chemokines in the mucosal fluids. Being able to boost local immune activities, these strategies could serve as strong adjuvants to amplify innate and effector responses to improve oral/nasal vaccination. With this approach we are in the midst of a preventative vaccine study designed to test whether C274 (vs the C661 control) increases the immunogenicity of aldrithiol 2 (AT-2) inactivated SIV (wild type wt vs deltaV1V2) when applied to the tonsillar tissues and if protective mucosal immunity is elicited. The treatment groups include (i) C274 + AT-2 SIV wt, (ii) C274 + AT-2 SIV deltaV1V2, (iii) control ODN C661 + AT-2 SIV wt, (iv) C661 + AT-2 SIV deltaV1V2, and (v) non-immunized animals. The animals were rectally challenged with infectious SIV 8 weeks after the last immunization. The non-immunized animals will also be challenged along side. After the first challenge, animals that remained uninfected were immunized once more and then rechallenged. All animals have now been challenged and the final immune (cellular and humoral) and viral parameters are being measured in blood and at mucosal surfaces.
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