title: A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART.
abstract: METHODS
  Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm3 and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART.
  
  
  METHODS
  The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination.
  
  
  RESULTS
  MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses.
  
  
  CONCLUSIONS
  MVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01571466.
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Carmen Elena
authors.initials: CE
authors.lastname: Gómez
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Perdiguero
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: García-Arriaza
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Cepeda
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Carlos Óscar
authors.initials: CÓ
authors.lastname: Sánchez-Sorzano
authors.affiliation: IrsiCaixa-HIVACAT, Hospital Universitari Germans Trias i Pujol, Autonomous University of Barcelona, Badalona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mothe
authors.affiliation: Hospital Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Jiménez
authors.affiliation: Hospital Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
authors.affiliation: Hospital Clinic-HIVACAT, IDIBAPS, Barcelona, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Hospital Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: López Bernaldo de Quirós
authors.affiliation: IrsiCaixa-HIVACAT, Hospital Universitari Germans Trias i Pujol, Autonomous University of Barcelona, Badalona, Spain.|Institució Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, and University of Vic and Central Catalonia, Vic, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.affiliation: Hospital Clinic-HIVACAT, IDIBAPS, Barcelona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
mesh_terms: D016915:AIDS Vaccines; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D010641:Phenotype; D014611:Vaccination
chemical_list: D016915:AIDS Vaccines