Transience of vaccine-induced HIV-1-specific CTL and definition of vaccine "response".
Many vaccine approaches emphasize producing HIV-1-specific CD8+ T-lymphocyte (CTL) responses. Towards this goal, many studies simply classify vaccinees as "responders" or "nonresponders," based on arbitrary cutoff criteria. HIV-1-uninfected participants receiving the TBC-3B vaccine were assessed for HIV-1-specific CTL by interferon-gamma ELISpot, and compared to HIV-1-infected control subjects not on antiretroviral therapy. Vaccinees also were tested for HIV-1-specific antibody responses and generalized CD8+ T-lymphocyte activation. Different criteria for vaccine "responder" status were applied to the measured CTL values. The vaccinees showed evidence of vaccine exposure by CD8+ T-lymphocyte activation and HIV-1-specific antibodies. Considering any single positive HIV-1-specific CTL measurement a vaccine "response," all vaccinees could be classified as "responders," but even slight increases in the stringency of response criteria resulted in a steep decline of the "response" rate. In contrast, HIV-1-infected persons were clearly "responders" against the same proteins by the same criteria. Quantitative assessment of CTL demonstrated low and transient HIV-1-specific CTL compared to natural infection. These analyses emphasize the pitfalls of summarizing vaccine study results using simple cutoff criteria to define response rates, and suggest the utility of more comprehensive descriptions to describe vaccine immunogenicity and persistence of responses.
UCLA AIDS Institute and Department of Medicine, Geffen School of Medicine, UCLA Medical Center, University of California, Los Angeles, CA 90095, and Department of Medicine, Massachusetts General Hospital, Boston 02114, USA.
Beth D
BD
Jamieson
F Javier
FJ
Ibarrondo
Johnson T
JT
Wong
Mary Ann
MA
Hausner
Hwee L
HL
Ng
Marie
M
Fuerst
Charles
C
Price
Roger
R
Shih
Julie
J
Elliott
Patricia M
PM
Hultin
Lance E
LE
Hultin
Peter A
PA
Anton
Otto O
OO
Yang
D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination
D016915:AIDS Vaccines; D015483:HIV Antibodies