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

doi:10.1016/j.virol.2009.09.012

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

Virology. 2009 Dec 5;395(1):45-55. doi: 10.1016/j.virol.2009.09.012. Epub 2009 Oct 2.

Authors

Paola Di Bonito¹, 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

Affiliation

¹ Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy.

PMID: 19800648
DOI: 10.1016/j.virol.2009.09.012

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 (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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptive Immunity
Animals
CD8-Positive T-Lymphocytes / immunology*
Cancer Vaccines / immunology*
Cell Line
Cross-Priming
HIV-1 / immunology
Human papillomavirus 16 / immunology
Humans
Membrane Glycoproteins / immunology
Mice
Mice, Inbred C57BL
Oncogene Proteins, Viral / immunology*
Papillomavirus E7 Proteins
Papillomavirus Infections / prevention & control
Papillomavirus Vaccines / immunology
Recombinant Fusion Proteins / immunology
Vesicular stomatitis Indiana virus / immunology
Viral Envelope Proteins / immunology
nef Gene Products, Human Immunodeficiency Virus / immunology*

Substances

Cancer Vaccines
G protein, vesicular stomatitis virus
Membrane Glycoproteins
Oncogene Proteins, Viral
Papillomavirus E7 Proteins
Papillomavirus Vaccines
Recombinant Fusion Proteins
Viral Envelope Proteins
nef Gene Products, Human Immunodeficiency Virus
nef protein, Human immunodeficiency virus 1
oncogene protein E7, Human papillomavirus type 16