Anti-tumor CD8+ T cell immunity elicited by HIV-1-based virus-like particles incorporating HPV-16 E7 protein

Autor: Felicia Grasso, Maurizio Federico, Claudia J. Dembek, Stefano M. Santini, Heinke Conrad, Giuseppe Laconi, Colomba Giorgi, Claudia Muratori, Armando Cesolini, Stefania Mochi, Paola Di Bonito, Emanuele Fanales-Belasio, Antonio Cosma, Arianna Mei, Helga Bernhard, Simona Donati, Caterina Lapenta, Linda Petrone
Rok vydání: 2009
Předmět:
Zdroj: Virology. 395(1):45-55
ISSN: 0042-6822
DOI: 10.1016/j.virol.2009.09.012
Popis: Here we report a novel strategy for the induction of CD8(+) T cell adaptive immune response against viral and tumor antigens. This approach relies on high levels of incorporation in HIV-1 VLPs of a mutant of HIV-1 Nef (Nef(mut)) which can act as anchoring element for foreign proteins. By in vitro assay, we found that VLP-associated Nef(mut) is efficiently cross-presented by antigen presenting cells. Inoculation in mice of VLPs incorporating the HPV-16 E7 protein fused to Nef(mut) led to an anti-E7 CD8(+) T cell response much stronger than that elicited by E7 recombinant protein inoculated with incomplete Freund's adjuvant and correlating with well-detectable anti-E7 CTL activity. Most relevantly, mice immunized with Nef(mut)-E7 VLPs developed a protective immune response against tumors induced by E7 expressing tumor cells. These results make Nef(mut) VLPs a promising candidate for new vaccine strategies focused on the induction of CD8(+) T cell immunity.
Databáze: OpenAIRE