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Journal of Virology, March 1999, p. 2280-2287, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Dissecting the Immune Response to Moloney Murine Sarcoma/Leukemia Virus-Induced Tumors by Means of a DNA Vaccination Approach

Gabriella Milan, Annalisa Zambon, Maria Cavinato, Paola Zanovello, Antonio Rosato,* and Dino Collavo

Immunology Section, Department of Oncology and Surgical Sciences, University of Padova, 35128 Padua, Italy

Received 10 August 1998/Accepted 16 November 1998

The intramuscular inoculation of Moloney murine sarcoma/leukemia (M-MSV/M-MuLV) retroviral complex gives rise to sarcomas that undergo spontaneous regression 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-MuLV in C57BL/6 (B6) mice and to evaluate whether plasmid DNA-immunized mice would be protected against a subsequent challenge with syngeneic tumor cells expressing the viral antigens. Intramuscular DNA vaccination induced CTL against both Gag and Env proteins. A detailed analysis of epitopes recognized by CTL generated in mice inoculated with the whole virus and with the Gag-expressing plasmid confirmed the presence of an immunodominant peptide in the leader sequence of Gag protein (Gag85-93, CCLCLTVFL) that is identical to that described in B6 mice immunized with Friend MuLV-induced leukemia cells. Moreover, CTL generated by immunization with the Env-encoding plasmid recognized a subdominant Env peptide (Env189-196, SSWDFITV), originally described in the B6.CH-2bm13 mutant strain. B6 mice immunized with the Gag-expressing plasmid were fully protected against a lethal tumor challenge 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 mice and in increased survival of an additional 17% of the animals. Taken together, these results indicate the existence of a hierarchy in the capacity of different structural viral proteins to induce a protective immune response against retrovirus-induced tumors.

* Corresponding author. Mailing address: Department of Oncology and Surgical Sciences, University of Padova, Via Gattamelata 64, I-35128 Padua, Italy. Phone: 39-49-8071859. Fax: 39-49-8072854. E-mail: arosato{at}ux1.unipd.it.

Journal of Virology, March 1999, p. 2280-2287, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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Copyright © 1999 by the American Society for Microbiology. All rights reserved.