Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1

Beatriz Mothe, Nuria Climent, Montserrat Plana, Miriam Rosàs, José Luis Jiménez, María Ángeles Muñoz-Fernández, María C. Puertas, Jorge Carrillo, Nuria Gonzalez, Agathe León, Judit Pich, Joan Albert Arnaiz, Jose M. Gatell, Bonaventura Clotet, Julià Blanco, José Alcamí, Javier Martinez-Picado, Carmen Alvarez-Fernández, Sonsoles Sánchez-Palomino, Alberto C. GuardoJosé Peña, José M. Benito, Norma Rallón, Beatriz Perdiguero, Juan García-Arriaza, Mariano Esteban, Juan Carlos López Bernaldo de Quirós, Christian Brander, Felipe García, Patricia Cobarsi, Carmen Alvarez, Sonsoles Sánchez, Lorna Leal, Berta Torres, Constanza Lucero, María Ángeles Muñoz-Fernández, Carmen Elena Gómez, Victoria Cepeda, Carlos Oscar Sánchez-Sorzano, Laura Jiménez

Research output: Contribution to journalArticleResearchpeer-review

42 Citations (Scopus)

Abstract

© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Objectives: The safety, immunogenicity, impact on the latent reservoir and rebound of viral load after therapeutic HIV-1 vaccination with recombinant modified vaccinia Ankara-based (MVA-B) HIV-1 vaccine expressing monomeric gp120 and the fused Gag-Pol-Nef polyprotein of clade B with or without a drug to reactivate latent HIV-1 (disulfiram) were assessed. Methods: HIV-1-infected patients were randomized to receive three injections of MVA-B (n1/420) or placebo (n1/410). Twelve patients (eight who received vaccine and four who were given placebo) received a fourth dose of MVA-B followed by 3 months of disulfiram. Combined ART (cART) was discontinued 8 weeks after the last dose of MVA-B. Clinical Trials.gov identifier: NCT01571466. Results: MVA-B was safe and well tolerated. A minor, but significant, increase in the T cell responses targeting vaccine inserts of Gag was observed [a median of 290, 403 and 435 spot-forming-cells/106 PBMCs at baseline, after two vaccinations and after three vaccinations, respectively; P1/40.02 and P1/40.04]. After interruption of cART, a modest delay in the rebound of the plasma viral load in participants receiving vaccine but not disulfiram was observed compared with placebo recipients (P1/40.01). The dynamics of the viral load rebound did not change in patients receiving MVA-B/disulfiram. No changes in the proviral reservoir were observed after disulfiram treatment. Conclusions: MVA-B vaccination was a safe strategy to increase Gag-specific T cell responses in chronically HIV-1- infected individuals, but it did not have a major impact on the latent reservoir or the rebound of plasma viral load after interruption of cART when given alone or in combination with disulfiram.
Original languageEnglish
Pages (from-to)1833-1842
JournalJournal of Antimicrobial Chemotherapy
Volume70
Issue number6
DOIs
Publication statusPublished - 12 Nov 2014

Keywords

  • Disulfiram
  • Functional cure
  • Poxvirus
  • Reservoir

Fingerprint

Dive into the research topics of 'Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1'. Together they form a unique fingerprint.

Cite this