Production and characterization of polarized dendritic cells aDC1 for use in anti-HIV immunotherapy

• Grant number: 18/12460-0
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): August 01, 2018
• Effective date (End): May 31, 2023
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Alberto José da Silva Duarte
• Grantee: Laís Teodoro da Silva
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/25212-9 - Therapeutic vaccine based on aDC1 dendritic cells pulsed with inactivated autologous virus for the control of viremia after ATI in HIV infected individuals, AP.TEM

Abstract

Immunotherapy based on Monocyte-Derived Dendritic Cells (MDDCs) is a promising strategy for the treatment of HIV-infected individuals. Due their plasticity, using different combinations of cytokines cocktail in vitro it is possible to obtain heterogeneous MDDCs populations. In the context of HIV infection is desirable obtaining MDDC able to secrete IL-12p70 in order to induce naïve T lymphocytes to differentiate into T cells secreting IFN-³ (Th1 profile). This study aims to produce and characterize an a-type-1-polarized dendritic cells (aDC1) based vaccine for HIV-infection. The aDC1 will be obtained from monocytes and differentiated into immature MDDCs in the presence of GM-CSF and IL-4 for 6 days. Subsequently, the cells will be incubated with aldrithiol-2-inactivated autologous HIV and cultured for additional 2 days with IFN-g and polyinosinic: polycytidylic acid (poly-I:C) plus a cocktail of cytokines composed of TNF-a, IL-1B, IL-6, IFN-a and PGE2. The autologous HIV will be isolated from HIV-1-infected individuals' Peripheral Blood Mononuclear Cells (PBMCs) and propagated in PBMCs from healthy volunteer donors. In order to characterized the vaccine product, phenotypic (expression of molecules involved in antigen presentation pathway, as for example, adhesion, costimulatory and migration molecules) and functional aspects (cytokines production, transmigration capacity and the ability to induce HIV-specific T cell responses) from precursors (monocytes) and from immature and mature aDC1 will be studied. Finally, the in vitro data will be correlated with results obtained from clinical protocol. (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)

DA SILVA, LAIS TEODORO; SANTILLO, BRUNA TERESO; DE ALMEIDA, ALEXANDRE; DA SILVA DUARTE, ALBERTO JOSE; OSHIRO, TELMA MIYUKI. Using Dendritic Cell-Based Immunotherapy to Treat HIV: How Can This Strategy be Improved?. FRONTIERS IN IMMUNOLOGY, v. 9, DEC 18 2018. (18/12460-0, 16/25212-9)

LUANDA MARA DA SILVA OLIVEIRA; BRUNA TIAKI TIYO; LAIS TEODORO DA SILVA; LUIZ AUGUSTO MARCONDES FONSECA; ROSANA COURA ROCHA; VERA APARECIDA DOS SANTOS; CARINA CENEVIVA; ANDERSON APARECIDO BEDIN; ALEXANDRE DE ALMEIDA; ALBERTO JOSÉ DA SILVA DUARTE; et al. Prevalence of anti-SARS-CoV-2 antibodies in outpatients of a large public university hospital in Sao Paulo, Brazil. Revista do Instituto de Medicina Tropical de São Paulo, v. 62, 2020-11-13. (16/25212-9, 18/12460-0, 19/07976-0)

DA SILVA, LAIS TEODORO; ORTEGA, MARINA MAZZILLI; TIYO, BRUNA TIAKI; TABOSA VIANA, ISABELLE FREIRE; DE LIMA, TAYNA EVILY; TOZETTO-MENDOZA, TANIA REGINA; DA SILVA OLIVEIRA, LUANDA MARA; EMIDIO TEIXEIRA, FRANCIANE MOURADIAN; LINS, ROBERTO DIAS; DE ALMEIDA, ALEXANDRE; et al. SARS-CoV-2 recombinant proteins stimulate distinct cellular and humoral immune response profiles in samples from COVID-19 convalescent patients. Clinics, v. 76, 2021. (18/12460-0, 16/25212-9)