Frontiers in Immunology (Nov 2021)

Effect of Intranodally Administered Dendritic Cell-Based HIV Vaccine in Combination With Pegylated Interferon α-2a on Viral Control Following ART Discontinuation: A Phase 2A Randomized Clinical Trial

  • Lorna Leal,
  • Lorna Leal,
  • Lorna Leal,
  • Elvira Couto,
  • Elvira Couto,
  • Sonsoles Sánchez-Palomino,
  • Núria Climent,
  • Irene Fernández,
  • Irene Fernández,
  • Laia Miralles,
  • Yolanda Romero,
  • Yolanda Romero,
  • Tania González,
  • Maria José Maleno,
  • Blanca Paño,
  • Judit Pich,
  • Carlos Nicolau,
  • Carlos Nicolau,
  • José Maria Gatell,
  • José Maria Gatell,
  • José Maria Gatell,
  • José Maria Gatell,
  • Montserrat Plana,
  • Montserrat Plana,
  • Felipe García,
  • Felipe García,
  • Felipe García,
  • the DCV3-RISVAC04 Study Group,
  • Lorna Leal,
  • Irene Fernández,
  • Elvira Couto,
  • Yolanda Romero,
  • Laia Miralles,
  • Carmen Hurtado,
  • Núria Climent,
  • Tania González,
  • Maria José Maleno,
  • Judit Pich,
  • Laura Burunat,
  • Joan Albert Arnaiz,
  • Blanca Paño,
  • Carlos Nicolau,
  • Rafael Salvador,
  • Elisabet Farré,
  • Sonsoles Sánchez-Palomino,
  • José Maria Gatell,
  • Montserrat Plana,
  • Felipe García,
  • Berta Torres,
  • Constanza Lucero,
  • Montserrat Laguno,
  • María Martínez-Rebollar,
  • Ana González-Cordón,
  • John Rojas,
  • Alexy Inciarte,
  • Lorena de la Mora,
  • Josep Mallolas,
  • Esteban Martínez,
  • José Luis Blanco,
  • Unai Perpiñá,
  • Josep Canals,
  • Raquel Martín,
  • Florencia Echeverry,
  • Cristina Xufré,
  • Cristina Rovira,
  • Marta Sala,
  • Amparo Tricas

DOI
https://doi.org/10.3389/fimmu.2021.767370
Journal volume & issue
Vol. 12

Abstract

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IntroductionFunctional cure has been proposed as an alternative to lifelong antiretroviral therapy and therapeutic vaccines represent one of the most promising approaches.Materials and MethodsWe 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.ResultsTwenty-nine male individuals on successful ART and with CD4+ ≥450 cells/mm3 were randomized 1:1:1:1 to receive three ultrasound-guided inguinal intranodal immunizations, one every 2 weeks: (1) vaccine ~107 MD-DC pulsed with HIA-HIV-1 (1010 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 (>0.5log10p = 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/106 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/106 PBMC, p = 0.04). No effect on T-cell responses or changes in viral reservoir were observed after INFα-2a administration.DiscussionResults 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

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