| Autor: |
Marcella Vassão de Almeida Baptista, Laís Teodoro da Silva, Sadia Samer, Telma Miyuki Oshiro, Iart Luca Shytaj, Leila B. Giron, Nathalia Mantovani Pena, Nicolly Cruz, Gisele Cristina Gosuen, Paulo Roberto Abrão Ferreira, Edécio Cunha-Neto, Juliana Galinskas, Danilo Dias, Maria Cecilia Araripe Sucupira, Cesar de Almeida-Neto, Reinaldo Salomão, Alberto José da Silva Duarte, Luís Mário Janini, James R. Hunter, Andrea Savarino, Maria Aparecida Juliano, Ricardo Sobhie Diaz |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
AIDS Research and Therapy, Vol 19, Iss 1, Pp 1-15 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1742-6405 |
| DOI: |
10.1186/s12981-021-00426-z |
| Popis: |
Abstract Background We developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses. Methods PBMCs were obtained from 10 HIV+ individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-α and GM-CSF. After sequencing each patient’s HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patients’ cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-γ) production were measured in CD4+ and CD8+ T-cells. Results The protocol of ex-vivo treatment with IFN-α and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4+ and CD8+ T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-γ expression was significantly increased in CD4+ T-cells. The number of candidates that increased in vitro the cytokine levels in CD4+ and CD8+ T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined. Conclusions MDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment. Trial registration NCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure, https://www.clinicaltrials.gov/ct2/show/NCT02961829 , posted November 11th, 2016) |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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