title: Dendritic cell-based therapeutic vaccine elicits polyfunctional HIV-specific T-cell immunity associated with control of viral load.
abstract: Efforts aimed at restoring robust immune responses limiting human immunodeficiency virus (HIV)-1 replication therapeutically are warranted. We report that vaccination with dendritic cells generated ex vivo and loaded with HIV lipopeptides in patients (n = 19) on antiretroviral therapy was well tolerated and immunogenic. Vaccination increased: (i) the breadth of the immune response from 1 (1-3) to 4 (2-5) peptide-pool responses/patient (p = 0.009); (ii) the frequency of functional T cells (producing at least two cytokines among IFN-γ, TNF-α, and IL-2) from 0.026 to 0.32% (p = 0.002) and from 0.26 to 0.35% (p = 0.005) for CD4(+) and CD8(+) T cells, respectively; and (iii) the breadth of cytokines secreted by PBMCs upon antigen exposure, including IL-2, IFN-γ, IL-21, IL-17, and IL-13. Fifty percent of patients experienced a maximum of viral load (VL) 1 log10 lower than the other half following antiretroviral treatment interruption. An inverse correlation was found between the maximum of VL and the frequency of polyfunctional CD4(+) T cells (p = 0.007), production of IL-2 (p = 0.006), IFN-γ (p = 0.01), IL-21 (p = 0.006), and IL-13 (p = 0.001). These results suggest an association between vaccine responses and a better control of viral replication. These findings will help in the development of strategies for a functional cure for HIV infection.
authors.affiliation: INSERM, Unite, Creteil, France; Universite Paris-Est, Creteil, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Henri-Mondor Albert-Chenevier, service d'immunologie clinique, Creteil, France; Vaccine Research Institute (VRI), Creteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Thiébaut
authors.forename: Monica
authors.initials: M
authors.lastname: Montes
authors.forename: Christine
authors.initials: C
authors.lastname: Lacabaratz
authors.forename: Louis
authors.initials: L
authors.lastname: Sloan
authors.forename: Bryan
authors.initials: B
authors.lastname: King
authors.forename: Sophie
authors.initials: S
authors.lastname: Pérusat
authors.forename: Carson
authors.initials: C
authors.lastname: Harrod
authors.forename: Amanda
authors.initials: A
authors.lastname: Cobb
authors.forename: Lee K
authors.initials: LK
authors.lastname: Roberts
authors.forename: Mathieu
authors.initials: M
authors.lastname: Surenaud
authors.forename: Céline
authors.initials: C
authors.lastname: Boucherie
authors.forename: Sandra
authors.initials: S
authors.lastname: Zurawski
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Laura
authors.initials: L
authors.lastname: Richert
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Karolina
authors.initials: K
authors.lastname: Palucka
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D055666:Lipopeptides / Q000008:administration & dosage*; D008297:Male; D014611:Vaccination; D019562:Viral Load / Q000187:drug effects* / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D055666:Lipopeptides
keywords: Antiretroviral therapy interruption; Dendritic cell; Lipopeptides; T cells; Vaccination