In:
Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-11-11)
Abstract:
Functional cure has been proposed as an alternative to lifelong antiretroviral therapy and therapeutic vaccines represent one of the most promising approaches. Materials and Methods We conducted a double-blind randomized placebo-controlled clinical trial to evaluate the safety, immunogenicity, and effect on viral dynamics of a therapeutic vaccine produced with monocyte-derived dendritic cells (MD-DC) loaded with a high dose of heat-inactivated autologous (HIA) HIV-1 in combination with pegylated interferon alpha 2a (IFNα-2a) in people with chronic HIV-1. Results Twenty-nine male individuals on successful ART and with CD4+ ≥450 cells/mm 3 were randomized 1:1:1:1 to receive three ultrasound-guided inguinal intranodal immunizations, one every 2 weeks: (1) vaccine ~10 7 MD-DC pulsed with HIA-HIV-1 (10 10 HIV RNA copies) ( n = 8); (2) vaccine plus three doses of 180 mcg IFNα-2a at weeks 4–6 ( n = 6); (3) placebo = saline ( n = 7); and (4) placebo plus three doses of 180 mcg IFNα-2a ( n = 8). Thereafter, treatment was interrupted (ATI). Vaccines, IFNα-2a, and the administration procedures were safe and well tolerated. All patients’ viral load rebounded during the 12-week ATI period. According to groups, changes in viral set-point between pre-ART and during ATI were not significant. When comparing all groups, there was a tendency in changes in viral set-point between the vaccine group vs. vaccine + IFNα-2a group ( & gt;0.5log 10 p = 0.05). HIV-1-specific T-cell responses (IFN-ƴ Elispot) were higher at baseline in placebo than in the vaccine group (2,259 ± 535 vs. 900 ± 200 SFC/10 6 PBMC, p = 0.028). A significant difference in the change of specific T-cell responses was only observed at week 4 between vaccine and placebo groups (694 ± 327 vs. 1,718 ± 282 SFC/10 6 PBMC, p = 0.04). No effect on T-cell responses or changes in viral reservoir were observed after INFα-2a administration. Discussion Results from this study show that intranodally administered DC therapeutic vaccine in combination with IFNα-2a was safe and well-tolerated but had a minimal impact on viral dynamics in HIV-1 chronic infected participants. Clinical Trial Registration ( www.ClinicalTrials.gov ), identifier NCT02767193
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2021.767370
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2606827-8
