Genetic vaccination with influenza virus recombinant containing CD8 epitope of Trypanosoma Cruzi

• Grant number: 19/21618-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2019
• End date: October 31, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jose Ronnie Carvalho de Vasconcelos
• Grantee: Cauê Cardoso Silva
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated research grant: 18/15607-1 - Role of specific CD4+ and CD8+ T cells generated by different vaccination protocols against experimental Trypanosoma cruzi infection, AP.JP2

Abstract

Natural infection by the intracellular protozoan Trypanosoma cruzi, the causative agent of Chagas disease, induces an immune response in the mammalian host that includes innate and adaptive immunity. Our group demonstrated that heterologous genetic immunization with T. cruzi ASP-2 and/or trans-sialidase generates a protective response against different models of experimental infection. This protocol induces strong cell-mediated immunity (MIC) in which specific CD4 + and CD8 + T cells play a key role. Moreover, we show that CD8 + T cells have phenotypic and functional characteristics of effector memory (TEM) T cells and that they need to recirculate to perform protective immune response in non-lymphoid peripheral tissues. Results obtained during the Young Researcher phase 1 project showed that the LFA-1 molecule plays a critical role in the migration of CD8 + T cells generated by heterologous genetic vaccination (Ferreira et al. 2017) as well as the CXCR3 molecule. In addition, CD8 + T cells specific to infected mice showed high expression of the CX3CR1 chemokine receptor. It has recently been reported that this molecule defines three subpopulations of CD8 + T cells during viral infections and is related to the differentiation of effector CD8 + T cells. Although CD4 + T cells play a fundamental role in protective immunity, few studies show a detailed study of the role of specific CD4 + T cells generated by immunization or infection. In view of this, the overall objective of this project will be build replication defective recombinant influenza viruses, carrying a 660 nucleotide fragment of the ASP-2 sequence, evaluate these recombinant viruses in recombinant adenovirus-associated vaccination protocols and analyze the immune response of specific CD8 + T cells. (AU)