title: A dendritic cell-based vaccine elicits T cell responses associated with control of HIV-1 replication.
abstract: Combination antiretroviral therapy (cART) greatly improves survival and quality of life of HIV-1-infected patients; however, cART must be continued indefinitely to prevent viral rebound and associated disease progression. Inducing HIV-1-specific immune responses with a therapeutic immunization has been proposed to control viral replication after discontinuation of cART as an alternative to "cART for life." We report safety, tolerability, and immunogenicity results associated with a control of viral replication for a therapeutic vaccine using autologous monocyte-derived dendritic cells (MD-DCs) pulsed with autologous heat-inactivated whole HIV. Patients on cART with CD4(+) >450 cells/mm(3) were randomized to receive three immunizations with MD-DCs or with nonpulsed MD-DCs. Vaccination was feasible, safe, and well tolerated and shifted the virus/host balance. At weeks 12 and 24 after cART interruption, a decrease of plasma viral load setpoint ≥1 log was observed in 12 of 22 (55%) versus 1 of 11 (9%) and in 7 of 20 (35%) versus 0 of 10 (0%) patients in the DC-HIV-1 and DC-control groups, respectively. This significant decrease in plasma viral load observed in immunized recipients was associated with a consistent increase in HIV-1-specific T cell responses. These data suggest that HIV-1-specific immune responses elicited by therapeutic DC vaccines could significantly change plasma viral load setpoint after cART interruption in chronic HIV-1-infected patients treated in early stages. This proof of concept supports further investigation of new candidates and/or new optimized strategies of vaccination with the final objective of obtaining a functional cure as an alternative to cART for life.
authors.affiliation: Hospital Clinic-IDIBAPS, HIVACAT, University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.forename: Nuria
authors.initials: N
authors.lastname: Climent
authors.forename: Alberto C
authors.initials: AC
authors.lastname: Guardo
authors.forename: Cristina
authors.initials: C
authors.lastname: Gil
authors.forename: Agathe
authors.initials: A
authors.lastname: León
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Picado
authors.forename: Judit
authors.initials: J
authors.lastname: Dalmau
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Josep M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallart
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry*; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D003713:Dendritic Cells / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D012367:RNA, Viral / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000821:virology*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication
chemical_list: D016915:AIDS Vaccines; D012367:RNA, Viral