Evaluation of cognate help provided by HIVBr27 in the generation of specific CD8+ T cell responses against Gag protein from HIV-1

• Grant number: 11/15312-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2011
• End date: October 31, 2012
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Edecio Cunha Neto
• Grantee: Adriana Dalben Faria
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The need for an effective vaccine against human immunodeficiency virus type 1 (HIV-1) is one of the priorities in research worldwide. So far, none of the experimental vaccines tested clinically in humans showed significant protection. Although CD8 + cytotoxic T lymphocyte anti-HIV-1 are those that effectively destroy virus-infected cells, its activity is primarily dependent on the presence of HIV-1 specific CD4+ T cells. Previously, our group selected 27 epitopes to CD4 + cells from conserved regions of the complete proteome of HIV-1 group M, that can bind to multiple HLA-DR molecules. Immunization of BALB /c mice with a DNA vaccine encoding such epitopes (HIVBr27) induced response of CD4 + T cells against multiple epitopes encoded by the vaccine. The hypothesis of this study is that pre-immunization with a vaccine encoding epitopes to CD4 + T cells of HIV-1 can provide cognate help and enhance responses of CD8 + T cells generated by subsequent vaccination with vaccines encoding entire HIV-1proteins. To adress this hypothesis, we will use the vaccine HIVBr27 containing 6 epitopes for CD4 + T cells from the Gag protein, being 4 epitopes from p24 region as a source of cognate help for the generation of Gag-specific CD8 + T cell responses by subsequent immunization with a plasmid encoding Gag or a recombinant protein, p24. The evaluation of antigen-specific cellular immune response will be performed by multiparametric flow cytometry and IFN-g ELISPOT assays. Such an approach will allow us to evaluate the potential of the HIVBr27vaccine as a source of cognate help for other vaccines against HIV-1 through its ability to potentiate cytotoxic / protective specific CD8 +T cell responses.