In vitro cellular immune response of HIV-1 infected individuals induced by dendritic cells expressing the CIITA factor and HIV-1 gag protein fused to DC-LAMP

• Grant number: 11/20649-6
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2012 - January 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Alberto José da Silva Duarte
• Grantee: Alberto José da Silva Duarte
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Telma Miyuki Oshiro Sumida

Abstract

Human Immunodeficiency Virus (HIV) infection leads to a deep deprivation of the immune system, mainly due to massive destruction of CD4 + T lymphocytes. Recently, several studies have demonstrated the potential use of dendritic cells (DCs) in therapeutic strategies to stimulate cellular immunity against HIV. In this project, we intend to evaluate the potential of dendritic cells derived from monocytes of HIV-infected individuals, transduced ex vivo with lentiviral vector, to stimulate cellular immune response in vitro. The lentiviral vector will consist of a sequence optimized for expression in human cells, which encodes for the co-expression of Gag protein fused to the DC-LAMP and the transcriptional activation factor CIITA. The expression of Gag fused to the DC-LAMP will target the antigen for the Major Histocompatibility Complex Class II (MHC II), whose expression will be increased by the CIITA factor stimulation. Transduced DCs will be assessed for the expression of vaccine antigen, CIITA factor and MHC molecules, as well as cell maturation and cytokine production. After that, these cells will be co-cultured with autologous lymphocytes, which will be analyzed for the production of IFN-³, TNF-±, MIP-1², IL-2 and the activation of cytotoxic T lymphocytes. The expectation is that this new vaccine strategy leverages the DCs ability to activate a specific T lymphocyte response against HIV. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PALMA, M. L.; DUANGKHAE, P.; DOURADINHA, B.; VIANA, I. F. T.; RIGATO, P. O.; DHALIA, R.; MAILLIARD, R. B.; BARRATT-BOYES, S. M.; NASCIMENTO, E. J. M.; OSHIRO, T. M.; et al. Development of potent class II transactivator gene delivery systems capable of inducing de novo MHC II expression in human cells, in vitro and ex vivo. Gene Therapy, v. 24, n. 6, p. 342-352, JUN 2017. (11/20649-6, 11/12134-6, 12/22171-9)