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.
OBJECTIVE
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 (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.


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/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.


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.
Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain 'Lluita contra la Sida' Foundation, Hospital Germans Trias i Pujol, Badalona, Spain Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic, Spain.
Beatriz
B
Mothe
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain.
Nuria
N
Climent
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain.
Montserrat
M
Plana
Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain.
Miriam
M
Rosàs
Hospital Gregorio Marañón, Madrid, Spain.
José Luis
JL
Jiménez
Hospital Gregorio Marañón, Madrid, Spain.
María Ángeles
MÁ
Muñoz-Fernández
Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain.
María C
MC
Puertas
Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain.
Jorge
J
Carrillo
AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid, Spain.
Nuria
N
Gonzalez
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain.
Agathe
A
León
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain.
Judit
J
Pich
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain.
Joan Albert
JA
Arnaiz
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain.
Jose M
JM
Gatell
Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain 'Lluita contra la Sida' Foundation, Hospital Germans Trias i Pujol, Badalona, Spain Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic, Spain.
Bonaventura
B
Clotet
Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic, Spain.
Julià
J
Blanco
AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid, Spain.
José
J
Alcamí
Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic, Spain Universitat Autònoma de Barcelona, Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Javier
J
Martinez-Picado
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain.
Carmen
C
Alvarez-Fernández
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain.
Sonsoles
S
Sánchez-Palomino
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain.
Alberto C
AC
Guardo
Hospital Reina Sofía, Córdoba, Spain.
José
J
Peña
Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Barcelona, Madrid, Spain.
José M
JM
Benito
Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Barcelona, Madrid, Spain.
Norma
N
Rallón
Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
Carmen E
CE
Gómez
Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
Beatriz
B
Perdiguero
Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
Juan
J
García-Arriaza
Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
Mariano
M
Esteban
Hospital Gregorio Marañón, Madrid, Spain.
Juan Carlos
JC
López Bernaldo de Quirós
Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic, Spain Universitat Autònoma de Barcelona, Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Christian
C
Brander
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain fgarcia@clinic.ub.es.
Felipe
F
García
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D004221:Disulfiram / Q000008:administration & dosage; D004337:Drug Carriers; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D010949:Plasma / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D004337:Drug Carriers; D015699:HIV Envelope Protein gp120; D010919:Placebos; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D054302:pol Gene Products, Human Immunodeficiency Virus; D004221:Disulfiram
disulfiram; functional cure; poxvirus; reservoir