title: A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic cells vs. canarypox-HIV alone in HIV-1-infected patients on antiretroviral therapy.
abstract: Targeting canarypox (CP)-HIV vaccine to dendritic cells (DCs) elicits anti-HIV-1 immune responses in vitro. We conducted a phase I/II clinical trial to evaluate whether adding DC to a CP-HIV vaccine improved virologic control during analytic treatment interruption (ATI) in HIV-1-infected subjects. Twenty-nine subjects on suppressive antiretroviral therapy were randomized to vaccination with autologous DCs infected with CP-HIV+keyhole limpet hemocyanin (KLH) (arm A, n=14) or CP-HIV+KLH alone (arm B, n=15). The mean viral load (VL) setpoint during ATI did not differ between subjects in arms A and B. A higher percentage of subjects in the DC group had a VL setpoint < 5,000 c/mL during ATI (4/13 or 31% in arm A compared with 0/13 in arm B, p=0.096), but virologic control was transient. Subjects in arm A had a greater increase in KLH lymphoproliferative response than subjects in arm B; however, summed ELISPOT responses to HIV-1 antigens did not differ by treatment arm. We conclude that a DC-CP-HIV vaccine is well-tolerated in HIV-1-infected patients, but does not lower VL setpoint during ATI compared with CP-HIV alone. New methods to enhance the immunogenicity and antiviral efficacy of DC-based vaccines for HIV-1 infection are needed.
authors.affiliation: Massachusetts General Hospital, 55 Fruit St, GRJ 504, Boston, MA 02114, United States. rgandhi@partners.org
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
authors.forename: David
authors.initials: D
authors.lastname: O'Neill
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Chan
authors.forename: R Pat
authors.initials: RP
authors.lastname: Bucy
authors.forename: Janet
authors.initials: J
authors.lastname: Shopis
authors.forename: Lynn
authors.initials: L
authors.lastname: Baglyos
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Adams
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fox
authors.forename: Lynette
authors.initials: L
authors.lastname: Purdue
authors.forename: Ann
authors.initials: A
authors.lastname: Marshak
authors.forename: Theresa
authors.initials: T
authors.lastname: Flynn
authors.forename: Reena
authors.initials: R
authors.lastname: Masih
authors.forename: Barbara
authors.initials: B
authors.lastname: Schock
authors.forename: Donna
authors.initials: D
authors.lastname: Mildvan
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Schlesinger
authors.forename: Mary A
authors.initials: MA
authors.lastname: Marovich
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D028121:Canarypox virus / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines; C468116:ALVAC-HIV vCP1452; D044966:Anti-Retroviral Agents; D015483:HIV Antibodies