Induction of CD8+ T Cell Responses to Dominant and Subdominant Epitopes and Protective Immunity to Sendai Virus Infection by DNA Vaccination

Abstract

While recent studies have demonstrated that DNA vaccination induces potent CD8+ T cell memory in vivo, it is unclear whether this memory is qualitatively and quantitatively comparable with that induced by natural viral infection. In the current studies, we have investigated the induction of CD8+ memory CTL responses to Sendai virus nucleoprotein (NP) in C57BL/6 mice following gene gun vaccination. The data demonstrate that this mode of vaccination induces potent long-lived memory CTL precursors (CTLp) specific for both the dominant (NP324-332/Kb) and the subdominant (NP324-332/Db) epitopes of NP. The frequencies of T cells specific for each of these epitopes in the spleen is about 1:2000 CD8+ T cells, similar to those induced by intranasal infection with Sendai virus. Moreover, the induction of memory CTLp by DNA vaccination is independent of MHC class II molecules or Ab, as is the case for memory CTLp induction by live Sendai virus infection. CTLp specific for both epitopes are capable of migrating to the lung following Sendai virus infection and express potent cytotoxic activity at the site of infection. Consistent with this activity, DNA vaccination with Sendai virus NP induced a substantial degree of Ab-independent protection from a challenge with a lethal dose of Sendai virus. Taken together, these data demonstrate that for the parameters tested, DNA vaccination is indistinguishable from live virus infection in terms of priming functional memory CTLp with broad specificity for both dominant and subdominant T cell epitopes.