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

被引:41
作者
Di Bonito, Paola [2 ]
Grasso, Felicia [2 ]
Mochi, Stefania [2 ]
Petrone, Linda [2 ]
Fanales-Belasio, Emanuele [1 ]
Mei, Arianna [2 ]
Cesolini, Armando [2 ]
Laconi, Giuseppe [2 ]
Conrad, Heinke [3 ]
Bernhard, Helga [3 ]
Dembek, Claudia J. [4 ]
Cosma, Antonio [4 ,5 ]
Santini, Stefano M. [6 ]
Lapenta, Caterina [6 ]
Donati, Simona [6 ]
Muratori, Claudia [1 ]
Giorgi, Colomba [2 ]
Federico, Maurizio [1 ]
机构
[1] Ist Super Sanita, Natl AIDS Ctr, I-00161 Rome, Italy
[2] Ist Super Sanita, Dept Infect Parasit & Immunomediated Dis, I-00161 Rome, Italy
[3] Tech Univ Munich, Klinikum Rechts Isar, Dept Hematol Oncol, D-8000 Munich, Germany
[4] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Virol, Neuherberg, Germany
[5] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Clin Cooperat Grp Immune Monitoring, Neuherberg, Germany
[6] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy
关键词
Virus-like particles; HPV-E7; CTLs; HIV-1; Nef; Cross-presentation; Protein delivery; CLASS-I MOLECULES; THERAPEUTIC VACCINATION; DENDRITIC CELLS; PLASMID DNA; NEF; ANTIGEN; GENERATION; VACCINES; NEUTRALIZATION; IMMUNIZATION;
D O I
10.1016/j.virol.2009.09.012
中图分类号
Q93 [微生物学];
学科分类号
071005 [微生物学];
摘要
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. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:45 / 55
页数:11
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