Enhanced sensitivity of detection of cytotoxic T lymphocyte responses to HIV type 1 proteins using an extended in vitro stimulation period for measuring effector function in volunteers enrolled in an ALVAC-HIV phase I/II prime boost vaccine trial in Thailand.
A phase I/II prime-boost vaccine trial in HIV-1-seronegative adults was conducted in Thailand using ALVAC-HIV (vCP1521) as a prime, boosting with either oligomeric gp160 TH023/LAI or Chiron HIV Thai subtype E (CM235) plus U. S. subtype B (SF2) gp120. Cytotoxic T lymphocyte (CTL) assays were conducted at one of the vaccine trial sites (Siriraj Hospital) at a single time point following the completion of immunization demonstrated that 8 of 50 (16%) vaccine recipients showed HIV-specific CTL by standard chromium release assay (CRA) after in vitro stimulation (IVS) for 2 weeks. Five additional vaccinees (13/50 = 26%) showed CTL responses after IVS for up to 4 weeks. Moreover, one volunteer with a positive CTL response to a single HIV antigen at Day 14 demonstrated a response to an additional HIV-1 antigen(s) after the longer IVS period. CTL activity was CD8+ restricted. Despite extension of the IVS up to 4 weeks, no CTL responses were detected in placebo recipients. These results imply that extension of the IVS period may increase the sensitivity of the CRA when measuring HIV-specific CTL in ALVAC-HIV prime-boost recipients without compromising specificity.
Kantakamalakul
Wannee
W
Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. siwkk@mahidol.ac.th
De Souza
Mark
M
Karnasuta
Chitraporn
C
Brown
Arthur
A
Gurunathan
Sanjay
S
Birx
Deborah
D
Thongcharoen
Prasert
P
Taveg
The
T
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002860:Chromium Radioisotopes; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D015685:Fusion Proteins, gag-pol / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D008213:Lymphocyte Activation; D012680:Sensitivity and Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013785:Thailand; D013997:Time Factors; D014611:Vaccination
D016915:AIDS Vaccines; D002860:Chromium Radioisotopes; D015685:Fusion Proteins, gag-pol; D015686:Gene Products, env