Cross-clade recognition and supressive effect induced by DNA vaccines encoding conserved and promiscuous HIV-1 M-group peptides

• Grant number: 12/03760-3
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): June 01, 2012
• Effective date (End): May 31, 2014
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal researcher: Edecio Cunha Neto
• Grantee: Rafael Ribeiro Almeida
• Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Induction of T-cell based immune responses has shown high potential against both SIV and HIV-1 infection and has become the focus of novel vaccine platforms. Mounting evidences suggest that CD4+ T-cells are important to viral control by either helping CD8+ T-cell-mediated immune responses or exerting direct citotoxic effect on infected cells, which make them interesting targets for vaccine constructs. HIV-1 genetic diversity is a barrier against development of broad protective vaccines and consensus sequences has been used to diminish genetic distances between imunogens and circulating variants. The target proteins used in vaccines also influence on infection control. Gag, Pol, Vif and Nef-specific cellular immune responses were associated with protection against infection while Env-specific responses were associated with progression to AIDS. Besides, both envelope proteins and peptides can induce suppression on cells of innate and acquire immunity. In order to induce broad CD4+ T-cell responses against multiple HIV-1 subtypes in diverse HLA-DR-bearing population, we previous identified 34 promiscuous peptides (predicted to bind to multiple HLA-DR molecules) and conserved in the HIV-1 M-group consensus sequence. We designed a DNA vaccine encoding 7 Env peptides (HIVenv7) and another vaccine encoding 27 peptides for the purpose of evaluating the influence of envelope-specific responses on vaccine formulations. HIVBr27 was immunogenic in BALB/c mice, eliciting broad and polyfunctional CD4+ and CD8+ T-cell responses. HIVenv7 was low immunogenic and showed to be able to suppress HIVBr27-induced immune responses when co-administered. In the present work we sought to determine the real capacity of binding of our 34 peptides to several HLA-DR, -DP, -DQ molecules and to murine IAb and IAd molecules. We aim to evaluate the frequency of peptide recognition by patients infected with different HIV-1 subtypes and the potential of HIVBr27 to induce cross-clade immune responses. Furthermore, we want to determine the protective capacity of HIVBr27 against recombinant vaccinia virus encoding HIV-1 proteins and to extend the studies on HIVenv7-mediated immunosuppression.