This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In these studies, we present unpublished new data demonstrating a novel approach to vaccine development in which we inactivate intact virus particles using hydrogen peroxide (H202). This approach preserves the antigenic structure of virus particles/proteins better than other commonly used inactivation techniques such as heat, formaldehyde, or UV cross-linking. To determine if hydrogen peroxide vaccines might be capable of inducing effective T cell memory, we have used LCMV (lymphocytic choriomeningitis virus) as a rigorous model system for characterizing vaccine-induced T cell responses. We show that MHC Class I-restricted LCMV NP118-specific CD8+ T cells are induced by a single dose of an H202-inactivated LCMV vaccine (without adjuvant) and achieve LCMV-specific CD8+ T cell numbers similar in magnitude to that induced by live recombinant vaccinia virus expressing the LCMV nucleoprotein antigen. H202-inactivated vaccines represent an entirely new approach to vaccine technology and have the potential for eliciting highly effective CD8+ T cell responses in addition to antigen-specific CD4+ T cell responses. In the proposed studies, we plan to test the effectiveness of clinically feasible adjuvants that augment antiviral immune responses through known interactions with specific Toll-Like Receptors (TLR) to determine the best approach for developing effective T cell vaccines.
The Specific Aims of this application include: I). Determine the inactivated vaccine regimen that elicits the best virus-specific T cell responses II). Determine the kinetics, phenotype, and immunodominance of vaccine-induced T cells III). Determine the antiviral functions of vaccine-induced T cells
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