INDUCTION OF CD8(-CELL RESPONSES TO DOMINANT AND SUBDOMINANT EPITOPESAND PROTECTIVE IMMUNITY TO SENDAI-VIRUS INFECTION BY DNA VACCINATION() T)

While recent studies have demonstrated that DNA vaccination induces po tent CD8(+) T cell memory in vivo, it is unclear whether this memory i s qualitatively and quantitatively comparable with that induced by nat ural viral infection, In the current studies, we have investigated the induction of CD8(+) memory CTL responses to Sendai virus nucleoprotei n (NP) in C57BL/6 mice following gene gun vaccination, The data demons trate that this mode of vaccination induces potent long-lived memory C TL precursors (CTLp) specific for both the dominant (NP324-332/K-b) an d the subdominant (NP324-332/D-b) epitopes of NP, The frequencies of T cells specific for each of these epitopes in the spleen is about 1:20 00 CD8(+) T cells, similar to those induced by intranasal infection wi th Sendai virus, Moreover, the induction of memory CTLp by DNA vaccina tion is independent of MHC class II molecules or Ab, as is the case fo r memory CTLp induction by live Sendai virus infection, CTLp specific for both epitopes are capable of migrating to the lung following Senda i 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 fr om a challenge with a lethal dose of Sendai virus, Taken together, the se data demonstrate that for the parameters tested, DNA vaccination is indistinguishable from live virus infection in terms of priming funct ional memory CTLp with broad specificity for both dominant and subdomi nant T cell epitopes.