Analysis of cellular immune response after in vivo targeting of HIV antigens to dendritic cells

• Grant number: 16/04842-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2016
• Effective date (End): December 31, 2016
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Daniela Santoro Rosa
• Grantee: Victória Alves Santos Lunardelli
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The epidemic caused by human immunodeficiency virus (HIV) is the most important emerging infection in the last decades. Despite advances in understanding the pathogenesis of the virus and the immune response against infection, there is no effective vaccine against HIV yet.Several lines of evidence indicate that antibodies, CD4 + and CD8 + T lymphocytes play a major role in immunity against HIV. In regard to vaccines based on the induction of cellular immunity, it is thought that the induction of broad and functional relevant immune responses against CD4+ and CD8+ T cell conserved epitopes, is an important requirement for new vaccine candidates. In previous studies, our group showed that mice immunization with a DNA vaccine encoding multiple CD4+ T cell epitopes from HIV-1 was able to induce broad, polyfunctional and long-term LTCD4+ and CD8+ responses. Although the results obtained with this vaccine formulation are quite promising promising, DNA vaccines have shown limited immunogenicity in humans. For this reason, in the recent years, different strategies and platforms for immunogens production have been developed. The ability of dendritic cells (DCs) to modulate the adaptive immune responses has also been the focus for vaccine development. In this context, the main goal of this project is to produce a chimeric monoclonal antibody against DC surface receptor (DEC205) fused to the HIV epitopes and test if this vaccine strategy is able to induce a specific cellular immune response with high magnitude and amplitude in vivo. To achieve this, BALB/c mice will be immunized with aDEC205-HIV antibody in the presence of poly I:C.