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

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.