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.

Medienart:

E-Artikel

Erscheinungsjahr:

2009

Erschienen:

2009

Enthalten in:

Zur Gesamtaufnahme - volume:395

Enthalten in:

Virology - 395(2009), 1 vom: 05. Dez., Seite 45-55

Sprache:

Englisch

Beteiligte Personen:

Di Bonito, Paola [VerfasserIn]
Grasso, Felicia [VerfasserIn]
Mochi, Stefania [VerfasserIn]
Petrone, Linda [VerfasserIn]
Fanales-Belasio, Emanuele [VerfasserIn]
Mei, Arianna [VerfasserIn]
Cesolini, Armando [VerfasserIn]
Laconi, Giuseppe [VerfasserIn]
Conrad, Heinke [VerfasserIn]
Bernhard, Helga [VerfasserIn]
Dembek, Claudia J [VerfasserIn]
Cosma, Antonio [VerfasserIn]
Santini, Stefano M [VerfasserIn]
Lapenta, Caterina [VerfasserIn]
Donati, Simona [VerfasserIn]
Muratori, Claudia [VerfasserIn]
Giorgi, Colomba [VerfasserIn]
Federico, Maurizio [VerfasserIn]

Links:

Volltext

Themen:

Cancer Vaccines
G protein, vesicular stomatitis virus
Journal Article
Membrane Glycoproteins
Nef Gene Products, Human Immunodeficiency Virus
Nef protein, Human immunodeficiency virus 1
Oncogene Proteins, Viral
Oncogene protein E7, Human papillomavirus type 16
Papillomavirus E7 Proteins
Papillomavirus Vaccines
Recombinant Fusion Proteins
Research Support, Non-U.S. Gov't
Viral Envelope Proteins

Anmerkungen:

Date Completed 24.11.2009

Date Revised 18.11.2010

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.virol.2009.09.012

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM191792675