Regulatory T cell abundance and activation status before and after priming with HIVIS-DNA and boosting with MVA-HIV/rgp140/GLA-AF may impact the magnitude of the vaccine-induced immune responses
Immunobiol., Suppl
; 223(12): 792-801, dez 2018. fig, tab
Article
em En
| RSDM
| ID: biblio-1523785
Biblioteca responsável:
MZ1.1
ABSTRACT
Little is known about regulatory CD4 T cells (Tregs) in the context of HIV vaccines. Tregs can be differentiated into resting (FoxP3+CD45RA+ - rTregs), activated (FoxP3HighCD45RA- - aTregs) and memory (FoxP3LowCD45RA- - mTregs). Tregs, as CD4 T cells, are also frequent targets for HIV infection. We studied how the abundance and phenotypes of Tregs in terms of activation status and expression of HIV-1 binding molecules would have changed during vaccination in healthy volunteers participating in a phase IIa HIV vaccine clinical trial. Subjects were primed three times with HIVIS-DNA and boosted twice with MVA-CMDR-HIV alone (n = 12) or MVA-CMDR combined with protein CN54rgp140 (n = 13). The proportions of ß7 integrin in all CD4 T cells and in the Tregs subset decreased moderately after the final vaccination (p = 0.001 and p = 0.033, respectively) and the rTregs proportion within the total Tregs were also decreased after the final vaccination (p = 0.038). All these proportions returned to normal values within the three months after the final vaccination. The magnitude of HIV-Envelope-specific IFNγ + T cells after vaccination (r = 0.66; p = 0.021) correlated directly with the proportion of Tregs, and correlated inversely correlated with ratios of Th17/Tregs (r = -0.75; p = 0.0057) and Th17/mTregs (r = -0.78; p = 0.0065). Higher titers of IgG gp140 antibodies were observed in subjects with higher mTregs proportions (r = 0.52; p = 0.022). Interestingly, pre-vaccination levels of mTregs correlated with vaccine-induced Env-binding antibodies (r = 0.57; p = 0.01) and presence of neutralizing antibodies (r = 0.61; p = 0.01), while the pre-vaccination Th17/mTregs ratio correlated inversely with the magnitude of cellular IFN-γ ELISpot responses (r = -0.9; p = 0.002). Taken together, these results suggest that pre- and post-vaccination Tregs, their activation status, the Th17/Tregs ratio and other host factors affecting Treg abundance, have an impact on the magnitude of HIV vaccine-induced immune responses. Moreover, the DNA-HIVIS/MVA-HIV regimen, alone or in combination with CN54rgp140 induced moderate and temporary alterations of the Tregs activation status. We also show a decrease in expression of the HIV-1 ligand ß7 integrin on Tregs and all CD4 T cells.
Palavras-chave
Texto completo:
1
Base de dados:
RSDM
Assunto principal:
Infecções por HIV
/
Citocinas
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HIV-1
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Vacinas contra a AIDS
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Linfócitos T CD8-Positivos
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Contagem de Linfócito CD4
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Vacinas de DNA
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
País como assunto:
Africa
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article