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

Paola Di Bonito, Felicia Grasso, Stefania Mochi, Linda Petrone, Emanuele Fanales-Belasio, Arianna Mei, Armando Cesolini, Giuseppe Laconi, Heinke Conrad, Helga Bernhard, Claudia J. Dembek, Antonio Cosma, Stefano M. Santini, Caterina Lapenta, Simona Donati, Claudia Muratori, Colomba Giorgi, Maurizio Federico

Research output: Contribution to journalArticlepeer-review

Abstract

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 (Nefmut) which can act as anchoring element for foreign proteins. By in vitro assay, we found that VLP-associated Nefmut is efficiently cross-presented by antigen presenting cells. Inoculation in mice of VLPs incorporating the HPV-16 E7 protein fused to Nefmut 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 Nefmut-E7 VLPs developed a protective immune response against tumors induced by E7 expressing tumor cells. These results make Nefmut VLPs a promising candidate for new vaccine strategies focused on the induction of CD8+ T cell immunity.

Original languageEnglish
Pages (from-to)45-55
Number of pages11
JournalVirology
Volume395
Issue number1
DOIs
Publication statusPublished - Dec 5 2009

Keywords

  • Cross-presentation
  • CTLs
  • HIV-1 Nef
  • HPV-E7
  • Protein delivery
  • Virus-like particles

ASJC Scopus subject areas

  • Virology

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