Study of the immunogenicity of the chimeric DNA DC-LAMP-1/p55Gag HIV-1 vaccine in neonates mice: induction of T follicular cells

• Grant number: 14/16756-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2014
• Effective date (End): September 30, 2015
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Maria Notomi Sato
• Grantee: Franciane Mouradian Emidio Teixeira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Strategies to enhance the neonatal immune response, induced by adjuvants or vaccines, in murine models has been the emphasis of the investigation in our research group. The chimeric DNA vaccine LAMP/p55gag of HIV-1 encoding the protein associate with membrane lisosomal-1 (LAMP-1) which drives the traffic of p55gag of HIV-1 to the MIIC compartments, favoring the viral peptides presentation through MHC class II, is immunogenic in adults and neonates mice, and crucial to induce long-lasting T and B cells response. The vaccine DC-LAMP/gag, that encodes human DC-LAMP does the targeting of Gag to the lysosomal/endosomal compartment of the dendritic cells (DCs), could be strategic to enhance the vaccinal response in the neonatal period. The proposal an immunogenic vaccine for HIV-1 in the neonatal period is to induce long-lasting response to cover until sexual maturity. Adjuvants inducers of type I IFN response could be an important alternative to over come the deficit of the neonates in the IL-12 / IFN-³ axis. Thus, the proposal is to evaluate the immunogenicity of the DNA vaccine DC-LAMP/gag and LAMP-gag in prime-boost schedule in newborn mouse, in the presence of ligand of STING (2'3'c-GAMP). The presence of Gag-specific CD8+ T cells, polyfunctional CD4+ and CD8+ T cells, antibody production and induction of CD4+ T follicular cells will be assessed. Moreover, to assess the efficacy of the vaccine, the long-lasting response will investigate after neonatal immunization. The knowledge of the neonatal immunology and vaccinal adjuvant strategies, could improve the pediatric vaccines.