A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic cells vs. canarypox-HIV alone in HIV-1-infected patients on antiretroviral therapy.
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.
Gandhi
Rajesh T
RT
Massachusetts General Hospital, 55 Fruit St, GRJ 504, Boston, MA 02114, United States. rgandhi@partners.org
O'Neill
David
D
Bosch
Ronald J
RJ
Chan
Ellen S
ES
Bucy
R Pat
RP
Shopis
Janet
J
Baglyos
Lynn
L
Adams
Elizabeth
E
Fox
Lawrence
L
Purdue
Lynette
L
Marshak
Ann
A
Flynn
Theresa
T
Masih
Reena
R
Schock
Barbara
B
Mildvan
Donna
D
Schlesinger
Sarah J
SJ
Marovich
Mary A
MA
Bhardwaj
Nina
N
Jacobson
Jeffrey M
JM
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
D016915:AIDS Vaccines; C468116:ALVAC-HIV vCP1452; D044966:Anti-Retroviral Agents; D015483:HIV Antibodies