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Virology ; 395(1): 45-55, 2009 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-19800648

RESUMO

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.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/imunologia , Proteínas Oncogênicas Virais/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana/imunologia , Imunidade Adaptativa , Animais , Linhagem Celular , Apresentação Cruzada , HIV-1/imunologia , Papillomavirus Humano 16/imunologia , Humanos , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas E7 de Papillomavirus , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Proteínas Recombinantes de Fusão/imunologia , Vírus da Estomatite Vesicular Indiana/imunologia , Proteínas do Envelope Viral/imunologia
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