Dissecting the immune response to moloney murine sarcoma/leukemia virus-induced tumors by means of a DNA vaccination approach

The intramuscular inoculation of Moloney murine sarcoma/leukemia (M-MSV/M-M uLV) retroviral complex gives rise to sarcomas that undergo spontaneous reg ression due to the induction of a strong immune reaction mediated primarily by cytotoxic T lymphocytes (CTL). We used a DNA-based vaccination approach to dissect the CTL response against the Gag and Env proteins of M-MSV/M-Mu LV in C57BL/6 (B6) mice and to evaluate whether plasmid DNA-immunized mice would be protected against a subsequent challenge with syngeneic tumor cell s expressing the viral antigens. Intramuscular DNA vaccination induced CTL against both Gag and Env proteins. A detailed analysis of epitopes recogniz ed by CTL generated in mice inoculated with the whole virus and with the Ga g-expressing plasmid confirmed the presence of an immunodominant peptide in the leader sequence of Gag protein (Gag(85-93), CCLCLTVFL) that is identic al to that described in B6 mice immunized with Friend MuLV-induced leukemia cells. Moreover, CTL generated by immunization with the Env-encoding plasm id recognized a subdominant Env peptide (Env(189-196), SSWDFITV), originall y described in the B6.CH-2(bm13) mutant strain. B6 mice immunized with the Gag-expressing plasmid were fully protected against a lethal tumor challeng e with M-MuLV-transformed MBL-2 leukemia cells, while vaccination with the Env-expressing plasmid resulted in rejection of the tumor in 44% of the mic e and in increased survival of an additional 17% of the animals. Taken toge ther, these results indicate the existence of a hierarchy in the capacity o f different structural viral proteins to induce a protective immune respons e against retrovirus-induced tumors.