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

被引:44
作者
Heeney, J
Åkerblom, L
Barnett, S
Bogers, W
Davis, D
Fuller, D
Koopman, G
Lehner, T
Mooij, P
Morein, B
Morghen, CD
Rosenwirth, B
Verschoor, E
Wagner, R
Wolf, H
机构
[1] Biomed Primate Res Ctr, Dept Virol, NL-2288 GH Rijswijk, Netherlands
[2] Swedish Univ Agr Sci, S-75123 Uppsala, Sweden
[3] Natl Vet Inst, Dept Virol, Ctr Biomed, S-75123 Uppsala, Sweden
[4] Chiron Corp, Emeryville, CA 94608 USA
[5] Inst Trop Med, Dept Microbiol, Virol Unit, B-2000 Antwerp, Belgium
[6] Powderject Vaccines, Madison, WI 53711 USA
[7] United Med & Dent Sch Guys & St Thomas Hosp, Guys Hosp, Dept Immunol, London SE1 9RT, England
[8] Univ Milan, Dept Pharmacol, Mol Virol Lab, I-20129 Milan, Italy
[9] Univ Regensburg, Inst Med Mikrobiol & Hyg, D-95053 Regensburg, Germany
关键词
HIV-1; vaccine; immunity; pre-clinical; immune responses; correlation;
D O I
10.1016/S0165-2478(98)00157-6
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:189 / 195
页数:7
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