Anti-HIV potency of T-cell responses elicited by dendritic cell therapeutic vaccination.
AIDS Vaccines
/ immunology
Adult
Anti-Retroviral Agents
Antiviral Agents
/ pharmacology
CD4-Positive T-Lymphocytes
/ immunology
CD8-Positive T-Lymphocytes
/ immunology
Dendritic Cells
/ immunology
Drug Therapy, Combination
/ methods
Epitopes
/ immunology
Epitopes, T-Lymphocyte
/ immunology
Female
HIV Infections
/ immunology
HIV-1
/ immunology
Humans
Interferon-alpha
/ metabolism
Male
Middle Aged
Vaccination
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
15
05
2019
accepted:
30
07
2019
entrez:
10
9
2019
pubmed:
10
9
2019
medline:
8
2
2020
Statut:
epublish
Résumé
Identification and characterization of CD8+ and CD4+ T-cell epitopes elicited by HIV therapeutic vaccination is key for elucidating the nature of protective cellular responses and mechanism of the immune evasion of HIV. Here, we report the characterization of HIV-specific T-cell responses in cART (combination antiretroviral therapy) treated HIV-1 infected patients after vaccination with ex vivo-generated IFNα Dendritic Cells (DCs) loaded with LIPO-5 (HIV-1 Nef 66-97, Nef 116-145, Gag 17-35, Gag 253-284 and Pol 325-355 lipopeptides). Vaccination induced and/or expanded HIV-specific CD8+ T cells producing IFNγ, perforin, granzyme A and granzyme B, and also CD4+ T cells secreting IFNγ, IL-2 and IL-13. These responses were directed against dominant and subdominant epitopes representing all vaccine regions; Gag, Pol and Nef. Interestingly, IL-2 and IL-13 produced by CD4+ T cells were negatively correlated with the peak of viral replication following analytic treatment interruption (ATI). Epitope mapping confirmed that vaccination elicited responses against predicted T-cell epitopes, but also allowed to identify a set of 8 new HIV-1 HLA-DR-restricted CD4+ T-cell epitopes. These results may help to better design future DC therapeutic vaccines and underscore the role of vaccine-elicited CD4+ T-cell responses to achieve control of HIV replication.
Identifiants
pubmed: 31498845
doi: 10.1371/journal.ppat.1008011
pii: PPATHOGENS-D-19-00899
pmc: PMC6733439
doi:
Substances chimiques
AIDS Vaccines
0
Anti-Retroviral Agents
0
Antiviral Agents
0
Epitopes
0
Epitopes, T-Lymphocyte
0
Interferon-alpha
0
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008011Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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