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.
Jamieson
Beth D
BD
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.
Ibarrondo
F Javier
FJ
Wong
Johnson T
JT
Hausner
Mary Ann
MA
Ng
Hwee L
HL
Fuerst
Marie
M
Price
Charles
C
Shih
Roger
R
Elliott
Julie
J
Hultin
Patricia M
PM
Hultin
Lance E
LE
Anton
Peter A
PA
Yang
Otto O
OO
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