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对含有灵长类动物CpG基序的HIV-1 DNA疫苗以及共表达IFNγ或IL-12的禽痘病毒疫苗在猕猴中的评估。

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

作者信息

Dale C Jane, De Rose Robert, Wilson Kim M, Croom Hayley A, Thomson Scott, Coupar Barbara E H, Ramsay Alistair, Purcell Damian F J, Ffrench Rosemary, Law Matthew, Emery Sean, Cooper David A, Ramshaw Ian A, Boyle David B, Kent Stephen J

机构信息

Department of Microbiology and Immunology, University of Melbourne, Royal Parade, Vic. 3010, Australia.

出版信息

Vaccine. 2004 Nov 25;23(2):188-97. doi: 10.1016/j.vaccine.2004.05.024.

Abstract

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 IFNgamma 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.

摘要

疫苗诱导的HIV特异性T细胞反应可能有助于有效控制HIV。质粒DNA疫苗和重组鸡痘病毒(rFPV)疫苗是很有前景的HIV-1疫苗候选物,尽管单独使用任何一种疫苗可能都不足以预防HIV-1。在30只猕猴中进一步评估了一种连续免疫策略,该策略包括先用DNA进行初免,然后用编码多种常见HIV-1抗原的rFPV疫苗进行加强免疫。DNA疫苗载体包含CpG免疫刺激分子,并将rFPV疫苗与共表达促T细胞细胞因子IFNγ或IL-12的rFPV疫苗进行比较。疫苗表达多种HIV-1基因,这些基因发生了突变以去除HIV蛋白的活性位点。疫苗耐受性良好,在rFPV加强免疫后,观察到DNA疫苗初免的HIV-1特异性T淋巴细胞反应显著增强。rFPV疫苗共表达IFNγ或IL-12并未进一步增强免疫反应。观察到对非致病性HIV-1攻击具有非灭菌性保护作用。本研究为产生针对HIV-1的T细胞介导免疫提供了一种安全、优化的策略的证据。

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