title: The HIV/AIDS vaccine candidate MVA-B administered as a single immunogen in humans triggers robust, polyfunctional, and selective effector memory T cell responses to HIV-1 antigens.
abstract: Attenuated poxvirus vectors expressing human immunodeficiency virus type 1 (HIV-1) antigens are considered promising HIV/AIDS vaccine candidates. Here, we describe the nature of T cell immune responses induced in healthy volunteers participating in a phase I clinical trial in Spain after intramuscular administration of three doses of the recombinant MVA-B-expressing monomeric gp120 and the fused Gag-Pol-Nef (GPN) polyprotein of clade B. The majority (92.3%) of the volunteers immunized had a positive specific T cell response at any time postvaccination as detected by gamma interferon (IFN-γ) intracellular cytokine staining (ICS) assay. The CD4(+) T cell responses were predominantly Env directed, whereas the CD8(+) T cell responses were similarly distributed against Env, Gag, and GPN. The proportion of responders after two doses of MVA-B was similar to that obtained after the third dose of MVA-B vaccination, and the responses were sustained (84.6% at week 48). Vaccine-induced CD8(+) T cells to HIV-1 antigens after 1 year were polyfunctional and distributed mainly within the effector memory (TEM) and terminally differentiated effector memory (TEMRA) T cell populations. Antivector T cell responses were mostly induced by CD8(+) T cells, highly polyfunctional, and of TEMRA phenotype. These findings demonstrate that the poxvirus MVA-B vaccine candidate given alone is highly immunogenic, inducing broad, polyfunctional, and long-lasting CD4 and CD8 T cell responses to HIV-1 antigens, with preference for TEM. Thus, on the basis of the immune profile of MVA-B in humans, this immunogen can be considered a promising HIV/AIDS vaccine candidate.
authors.affiliation: Centro Nacional de Biotecnología, CSIC, Madrid 28049, Spain.
authors.forename: Carmen Elena
authors.initials: CE
authors.lastname: Gómez
authors.forename: José Luis
authors.initials: JL
authors.lastname: Nájera
authors.forename: Beatriz
authors.initials: B
authors.lastname: Perdiguero
authors.forename: Juan
authors.initials: J
authors.lastname: García-Arriaza
authors.forename: Carlos Oscar S
authors.initials: CO
authors.lastname: Sorzano
authors.forename: Victoria
authors.initials: V
authors.lastname: Jiménez
authors.forename: Rubén
authors.initials: R
authors.lastname: González-Sanz
authors.forename: José Luis
authors.initials: JL
authors.lastname: Jiménez
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernández
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: López Bernaldo de Quirós
authors.forename: Alberto C
authors.initials: AC
authors.lastname: Guardo
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D004337:Drug Carriers; D005822:Genetic Vectors; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007156:Immunologic Memory; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D013030:Spain; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination / Q000379:methods; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D015488:HIV Antigens; D007371:Interferon-gamma