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^*

^*Corresponding author for this work

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

44 Citations (Scopus)

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 - 5 Dec 2009
Externally published	Yes

Keywords

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

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10.1016/j.virol.2009.09.012

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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

@article{8759f3c68aa64177ba9eb8d9b6e45d58,

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

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.",

keywords = "CTLs, Cross-presentation, HIV-1 Nef, HPV-E7, Protein delivery, Virus-like particles",

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

note = "Funding Information: This work was supported by grants from the AIDS project of the Ministry of Health, Rome, Italy. Recombinant HIV-1 Gag protein was obtained from NIH AIDS Research and Reference Reagent Program. We are indebted to Rosella Franconi (ENEA, Rome, Italy) for providing the plasmid carrying the E7 GGG open reading frame. We thank Maria Ferrantini, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit{\`a}, Rome, Italy, for helpful discussions and critically reading the manuscript and to Julia Neudorfer and Simone Allgayer for excellent technical assistance. We are indebted to Federica M. Regini for the excellent editorial assistance.",

year = "2009",

month = dec,

day = "5",

doi = "10.1016/j.virol.2009.09.012",

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journal = "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, 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

TY - JOUR

T1 - Anti-tumor CD8+ T cell immunity elicited by HIV-1-based virus-like particles incorporating HPV-16 E7 protein

AU - Di Bonito, Paola

AU - Grasso, Felicia

AU - Mochi, Stefania

AU - Petrone, Linda

AU - Fanales-Belasio, Emanuele

AU - Mei, Arianna

AU - Cesolini, Armando

AU - Laconi, Giuseppe

AU - Conrad, Heinke

AU - Bernhard, Helga

AU - Dembek, Claudia J.

AU - Cosma, Antonio

AU - Santini, Stefano M.

AU - Lapenta, Caterina

AU - Donati, Simona

AU - Muratori, Claudia

AU - Giorgi, Colomba

AU - Federico, Maurizio

N1 - Funding Information: This work was supported by grants from the AIDS project of the Ministry of Health, Rome, Italy. Recombinant HIV-1 Gag protein was obtained from NIH AIDS Research and Reference Reagent Program. We are indebted to Rosella Franconi (ENEA, Rome, Italy) for providing the plasmid carrying the E7 GGG open reading frame. We thank Maria Ferrantini, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy, for helpful discussions and critically reading the manuscript and to Julia Neudorfer and Simone Allgayer for excellent technical assistance. We are indebted to Federica M. Regini for the excellent editorial assistance.

PY - 2009/12/5

Y1 - 2009/12/5

N2 - 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.

AB - 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.

KW - CTLs

KW - Cross-presentation

KW - HIV-1 Nef

KW - HPV-E7

KW - Protein delivery

KW - Virus-like particles

UR - https://www.scopus.com/pages/publications/71749116038

U2 - 10.1016/j.virol.2009.09.012

DO - 10.1016/j.virol.2009.09.012

M3 - Article

C2 - 19800648

AN - SCOPUS:71749116038

SN - 0042-6822

VL - 395

SP - 45

EP - 55

JO - Virology

JF - Virology

IS - 1

ER -

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

Abstract

Keywords

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