HIV-1 vaccine-induced immune responses which correlate with protection from SHIV infection: compiled preclinical efficacy data from trials with ten different HIV-1 vaccine candidates.
The specific immune mechanisms necessary and/or sufficient to elicit HIV-vaccine protection remain undefined. Utilising the SHIV rhesus macaque model the immunogenicity as well as the efficacy of ten different HIV-1 vaccine candidates was evaluated. Comparison of the immune responses induced, with the ability of the vaccine to protect from SHIV infection provided a means to determine which type of immune responses were necessary for protection. Vaccine candidates included VLPs, DNA, subunit protein with novel adjuvant formulations, ISCOMs and pox-virus vectors. Protection from SHIV infection was achieved in approximately half of the animals which received a primary intravenous cell-free challenge. The presence of CTL in the absence of other effector responses did not correlate with protection from this route and type of challenge. Virus neutralising antibodies (Nab) appeared to be necessary but alone were insufficient for protection. If Ag-specific IFN-gamma and/or IL-4 as well as lymphoproliferative (LP) responses were found with the lack of a detectable IL-2 response, then protection was not observed. Immunity correlated with the magnitude of Nab responses, beta-chemokines and as well as balanced, qualitative T-helper responses.
Heeney
J
J
Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands. heeney@bprc.nl
Akerblom
L
L
Barnett
S
S
Bogers
W
W
Davis
D
D
Fuller
D
D
Koopman
G
G
Lehner
T
T
Mooij
P
P
Morein
B
B
de Giuli Morghen
C
C
Rosenwirth
B
B
Verschoor
E
E
Wagner
R
R
Wolf
H
H
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D019742:Chemokines, CC / Q000276:immunology; D002986:Clinical Trials as Topic; D015483:HIV Antibodies / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008253:Macaca mulatta; D009500:Neutralization Tests; D016865:Reassortant Viruses / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016915:AIDS Vaccines; D019742:Chemokines, CC; D015483:HIV Antibodies