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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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