Induction of HIV‐Specific T Cell Responses Using αDC1 Pulsed With Conserved HIV‐1 Peptides

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Abstract
Despite the effectiveness of antiretroviral therapy (ART) in suppressing HIV‐1 replication and reducing morbidity, viral eradication remains unachievable due to the persistence of latent reservoirs, particularly within memory CD4 + T cells. Dendritic cell (DC)‐based immunotherapeutic approaches have emerged as potential strategies to enhance antigen‐specific immune responses against HIV‐1. In this context, alpha‐type‐1 polarized DCs (αDC1) are notable for their capacity to produce interleukin‐12p70 (IL‐12p70) and induce robust Th1 and cytotoxic T lymphocyte (CTL) responses. However, clinical outcomes have been inconsistent, often influenced by host factors and methodological variability in DC generation and antigen delivery. The high genetic diversity of HIV poses challenges for vaccine development, whereas conserved regions such as gag and pol represent promising immunogenic targets. The present study aimed to evaluate a set of previously identified conserved HIV‐1 peptides for their ability to stimulate HIV‐specific T cell responses when presented by αDC1 in vitro in coculture assays using samples from a Brazilian cohort, as part of a preparatory phase for a clinical trial. For this purpose, monocytes were differentiated into αDC1 using IL‐4 and GM‐CSF. On Day 5, the cells were pulsed with 14–21mer HIV‐1 peptide pools (gag and pol) and matured by the addition of IFN‐α, IFN‐γ, IL‐1β, and TNF‐α. After 48 h, αDC1 were harvested and cocultured with autologous T cells for 6 or 20 days. Pulsed‐αDC1 were able to induce immune responses through the production of IFN‐γ in T cells, with the subpopulation of effector memory CD4 + T cells ( T EM ) being responsible for the production of this cytokine after reexposure to the HIV antigens.
Funding Information
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (16/25212-9)
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (24/14088-1)
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (23/11990-3)
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (23/14374-1)
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (25/12297-5)
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (25/13425-7)
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (25/03433-2)
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (21/06139-7)
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (24/08802-3)
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (24/08360-0)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (88887.970045/2024-00)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (88887.196649/2025-00)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (138377/2025-1)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (88887.251198/2026-00)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (303384/2024-7)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (304043/2022-2)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (305135/20198)

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