Imunoterapia Anti-HIV baseada em células dendríticas: análise fenotípica e resposta imune celular pós vacinal

• Ano de defesa: 2020
• Autor(a) principal: Baptista, Marcella Vassao De Almeida [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: HIV; Imunoterapia; Células Dendríticas; Citometria De Fluxo
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=9344103; https://hdl.handle.net/11600/64714

The obstacles to the sterilizing cure of HIV infection among patients with antiretrovirals are a proven residual viral replication of the same “sanctuaries” of HIV-1 and cell / viral latency. This work is part of a project that aims to try to eradicate HIV infection with the use of related restrictions. Our object of study was immunologically used in monocyte-derived dendritic cells (MDDCs), which adopted a promising strategy for the treatment of HIV-infected individuals, in an attempt to select infected cells in sanctuary sites Objective: To characterize the immunogenicity of the vaccine product by autonomous monocyte-derived dendritic cells (MDDCs), HIV-infected individuals, stimulated with autologous peptides. Methods: Ten HIV-infected individuals were immunized. Peripheral blood mononuclear cells (PBMCs) were destroyed by leukapheresis. Monocytes were differentiated into DCs with the presence of IFN-α and GM-CSF. How DCs were stimulated with autologous peptides. Three doses of the vaccine were injected into the patients' axillary and inguinal subcutaneous regions every 2 weeks. Six hours before inoculation in patients, as MDDCs were activated by the addition of lipopolysaccharide (LPS). Phenotypic analyzes of the vaccine product were performed. HIV-specific T cell responses were assessed after 48 hours of incubation with autologous peptides. As patient samples were collected at the time of the first dose of the vaccine (day 0), at the time of the second dose of the vaccine (day 14, reflecting the impact of the first dose of the vaccine), at the time of the 3rd dose of the vaccine (day 28) , reflecting the impact of the 2nd vaccine dose) and 2 months after the 3rd vaccine dose (day 90). How the patient's cells were stimulated with autologous peptides used to sensitize as MDDCs, and IL2, TNF and IFN- were measured by flow cytometry on CD4 + T cells and CD8 + T cells. As for the control experiment, how the patient's cells were stimulated with S aureus type B enterotoxin (SEB) and brefaldine (BFA). Results: Compared to immature cells, as mature MoDCs show a profile with increased expression of HLA-DR, CD 86, CD80, CCR7, CD40 and CD83. Regarding HIV-specific T cell responses, there was a significant increase in interleukin measurements from day zero to day 14 and 14 to 28 in CD4 + T cells (IL-2 p = 0.008, TNF p = 0.0002 and IFN p = 0.005) and a significant increase in the measurements of IL2 (p = 0.002)and TNF (p = 0.003) from day zero to day 14 and 14 to 28 (Kruskal-Wallis). Conclusion: Collectively, the results shown by the MDDCs used in the vaccine have a mature profile and this intervention promotes an in vitro immune response in HIV-infected patients.