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

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

Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani

Research output: Contribution to journal › Article › peer-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 (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.

Original language	English
Pages (from-to)	45-55
Number of pages	11
Journal	Virology
Volume	395
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2009.09.012
Publication status	Published - 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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Di Bonito, P., Grasso, F., Mochi, S., Petrone, L., Fanales-Belasio, E., Mei, A., Cesolini, A., Laconi, G., Conrad, H., Bernhard, H., Dembek, C. J., Cosma, A., Santini, S. M., Lapenta, C., Donati, S., Muratori, C., Giorgi, C., & Federico, M. (2009). Anti-tumor CD8+ T cell immunity elicited by HIV-1-based virus-like particles incorporating HPV-16 E7 protein. Virology, 395(1), 45-55. https://doi.org/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. / Di Bonito, Paola; Grasso, Felicia; Mochi, Stefania; Petrone, Linda; Fanales-Belasio, Emanuele; Mei, Arianna; Cesolini, Armando; Laconi, Giuseppe; Conrad, Heinke; Bernhard, Helga; Dembek, Claudia J.; Cosma, Antonio; Santini, Stefano M.; Lapenta, Caterina; Donati, Simona; Muratori, Claudia; Giorgi, Colomba; Federico, Maurizio.

In: Virology, Vol. 395, No. 1, 05.12.2009, p. 45-55.

Research output: Contribution to journal › Article › peer-review

Di Bonito, P, Grasso, F, Mochi, S, Petrone, L, Fanales-Belasio, E, Mei, A, Cesolini, A, Laconi, G, Conrad, H, Bernhard, H, Dembek, CJ, Cosma, A, Santini, SM, Lapenta, C, Donati, S, Muratori, C, Giorgi, C & Federico, M 2009, 'Anti-tumor CD8+ T cell immunity elicited by HIV-1-based virus-like particles incorporating HPV-16 E7 protein', Virology, vol. 395, no. 1, pp. 45-55. https://doi.org/10.1016/j.virol.2009.09.012

Di Bonito, Paola ; Grasso, Felicia ; Mochi, Stefania ; Petrone, Linda ; Fanales-Belasio, Emanuele ; Mei, Arianna ; Cesolini, Armando ; Laconi, Giuseppe ; Conrad, Heinke ; Bernhard, Helga ; Dembek, Claudia J. ; Cosma, Antonio ; Santini, Stefano M. ; Lapenta, Caterina ; Donati, Simona ; Muratori, Claudia ; Giorgi, Colomba ; Federico, Maurizio. / Anti-tumor CD8+ T cell immunity elicited by HIV-1-based virus-like particles incorporating HPV-16 E7 protein. In: Virology. 2009 ; Vol. 395, No. 1. pp. 45-55.

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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.",

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AU - Fanales-Belasio, Emanuele

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

Abstract

Keywords

ASJC Scopus subject areas

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