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 (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.
Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Paola
P
Di Bonito
Felicia
F
Grasso
Stefania
S
Mochi
Linda
L
Petrone
Emanuele
E
Fanales-Belasio
Arianna
A
Mei
Armando
A
Cesolini
Giuseppe
G
Laconi
Heinke
H
Conrad
Helga
H
Bernhard
Claudia J
CJ
Dembek
Antonio
A
Cosma
Stefano M
SM
Santini
Caterina
C
Lapenta
Simona
S
Donati
Claudia
C
Muratori
Colomba
C
Giorgi
Maurizio
M
Federico
D056704:Adaptive Immunity; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D045142:Cross-Priming; D015497:HIV-1 / Q000276:immunology; D052162:Human papillomavirus 16 / Q000276:immunology; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D019496:Cancer Vaccines; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C059731:oncogene protein E7, Human papillomavirus type 16