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

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 reactiv...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2015-06, Vol.70 (6), p.1833-1842
Main Authors: Mothe, Beatriz, Climent, Nuria, Plana, Montserrat, Rosàs, Miriam, Jiménez, José Luis, Muñoz-Fernández, María Ángeles, Puertas, María C, Carrillo, Jorge, Gonzalez, Nuria, León, Agathe, Pich, Judit, Arnaiz, Joan Albert, Gatell, Jose M, Clotet, Bonaventura, Blanco, Julià, Alcamí, José, Martinez-Picado, Javier, Alvarez-Fernández, Carmen, Sánchez-Palomino, Sonsoles, Guardo, Alberto C, Peña, José, Benito, José M, Rallón, Norma, Gómez, Carmen E, Perdiguero, Beatriz, García-Arriaza, Juan, Esteban, Mariano, López Bernaldo de Quirós, Juan Carlos, Brander, Christian, García, Felipe
Format: Article
Language:English
Subjects:
Adult
AIDS Vaccines - administration & dosage
AIDS Vaccines - adverse effects
AIDS Vaccines - immunology
Anti-HIV Agents - administration & dosage
Disulfiram - administration & dosage
Drug Carriers
Female
gag Gene Products, Human Immunodeficiency Virus - genetics
gag Gene Products, Human Immunodeficiency Virus - immunology
HIV
HIV Envelope Protein gp120 - genetics
HIV Envelope Protein gp120 - immunology
HIV Infections - therapy
HIV-1 - genetics
HIV-1 - immunology
HIV-1 - isolation & purification
Human immunodeficiency virus
Humans
Immunization
Male
Medical treatment
Middle Aged
nef Gene Products, Human Immunodeficiency Virus - genetics
nef Gene Products, Human Immunodeficiency Virus - immunology
Placebos - administration & dosage
Plasma - virology
pol Gene Products, Human Immunodeficiency Virus - genetics
pol Gene Products, Human Immunodeficiency Virus - immunology
Proteins
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - immunology
T cell receptors
Vaccination - methods
Vaccines
Vaccines, Synthetic - administration & dosage
Vaccines, Synthetic - adverse effects
Vaccines, Synthetic - immunology
Vaccinia virus - genetics
Viral Load
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Summary: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. HIV-1-infected patients were randomized to receive three injections of MVA-B (n = 20) or placebo (n = 10). 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. 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/10(6) PBMCs at baseline, after two vaccinations and after three vaccinations, respectively; P = 0.02 and P = 0.04]. 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 (P = 0.01). 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. 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.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkv046