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 In these studies, we present unpublished new data demonstrating a novel approach to vaccine development in which we inactivate intact virus particles using hydrogen peroxide (H202).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 have demonstrated that vaccination with H2O2-inactivated LCMV induces a readily detectable virus-specific CD8+ T cell response that is multi-functional and capable of cytokine production (IFN, TNF, and IL-2) as well as in vivo CTL activity against peptide-coated targets. Moreover, we have demonstrated that mice that receive this vaccine are able to generate virus-specific CD8+ T cells that rapidly proliferate following live virus challenge and are able to clear chronic LCMV clone 13 infection, indicating that the antiviral T cell response elicited by this vaccine is protective against chronic viral infection.
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