Evaluation in macaques of HIV-1 DNA vaccines containing primate CpG motifs and fowlpoxvirus vaccines co-expressing IFNγ or IL-12

被引:45
作者
Dale, CJ
De Rose, R
Wilson, KM
Croom, HA
Thomson, S
Coupar, BEH
Ramsay, A
Purcell, DFJ
Ffrench, R
Law, M
Emery, S
Cooper, DA
Ramshaw, IA
Boyle, DB
Kent, SJ [1 ]
机构
[1] Univ Melbourne, Dept Microbiol & Immunol, Royal Parade, Vic 3010, Australia
[2] St Vincents Inst Med Res, Natl Serol Reference Lab, Fitzroy, Vic 3065, Australia
[3] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia
[4] CSIRO, Livestock Ind, Geelong, Vic 3220, Australia
[5] Univ Newcastle, Discipline Immunol & Microbiol, Newcastle, NSW 2300, Australia
[6] Sydeny Childrens Hosp, Dept Immunol & Infect Dis, Randwick, NSW 2031, Australia
[7] Univ New S Wales, Sch Womens & Childrens Hlth, Fac Med, Sydney, NSW 2052, Australia
[8] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW 2010, Australia
基金
美国国家卫生研究院;
关键词
vaccine; DNA; recombinant fowlpoxvirus; prime/boost; macaque; cytokine co-expression;
D O I
10.1016/j.vaccine.2004.05.024
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Induction of HIV-specific T-cell responses by vaccines may facilitate efficient control of HIV. Plasmid DNA vaccines and recombinant fowlpoxvirus (rFPV) vaccines are promising HIV-1 vaccine candidates, although either vaccine alone may be insufficient to protect against HIV-1. A consecutive immunisation strategy involving priming with DNA and boosting with rFPV vaccines encoding multiple common HIV-1 antigens was further evaluated in 30 macaques. The DNA vaccine vector included CpG immunostimulatory molecules, and rFPV vaccines were compared with rFPV vaccines co-expressing the pro-T cell cytokines IFN-gamma or IL-12. Vaccines expressed multiple HIV-1 genes, mutated to remove active sites of the HIV proteins. The vaccines were well tolerated, and a significant enhancement of DNA-vaccine primed HIV-1 specific T lymphocyte responses was observed following rFPV boosting. Co-expression of IFNgamma or IL-12 by the rFPV vaccines did not further enhance immune responses. Non-sterilising protection from a non-pathogenic HIV-1 challenge was observed. This study provides evidence of a safe, optimised, strategy for the generation of T-cell mediated immunity to HIV-1. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:188 / 197
页数:10
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