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用共表达γ干扰素的重组鸡痘病毒对猕猴进行治疗性疫苗接种后,诱导HIV-1特异性T辅助反应和1型细胞因子分泌。

Induction of HIV-1-specific T-helper responses and type 1 cytokine secretion following therapeutic vaccination of macaques with a recombinant fowlpoxvirus co-expressing interferon-gamma.

作者信息

Dale C J, Zhao A, Jones S L, Boyle D B, Ramshaw I A, Kent S J

机构信息

AIDS Pathogenesis Research Unit, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria, Australia.

出版信息

J Med Primatol. 2000 Aug;29(3-4):240-7. doi: 10.1034/j.1600-0684.2000.290317.x.

Abstract

Preventive and/or therapeutic vaccines against Human Immunodeficiency Virus (HIV-1) are urgently required. Induction of cellular immunity is favoured since these responses correlate with control of HIV-1. Recombinant fowlpoxvirus (FPV) vaccines encoding both HIV-1 gag/pol and interferon-gamma (FPV gag/pol-IFNgamma) were hypothesised to enhance HIV-specific cellular immunity and were further evaluated in macaques previously infected with HIV-1. A novel assay to detect IFNgamma secretion following HIV antigen stimulation of whole blood was developed to further assess the safety and immunogenicity of the FPV gag/pol-IFNgamma vaccine. Immunisation with FPV gag/pol-IFNgamma safely enhanced HIV-specific IFNgamma secretion following ex vivo stimulation of whole blood, greater than that observed following FPV gag/pol vaccination not co-expressing IFNgamma. Both HIV-specific IFNgamma-spot-forming cells by ELISPOT and CD69 expression by CD4+ lymphocytes were also enhanced following FPV gag/pol-IFNgamma vaccination. Hence, the FPV-HIV vaccine co-expressing IFNgamma stimulated HIV-specific T cell responses in macaques, and should be further evaluated as a therapeutic or preventive HIV vaccine.

摘要

迫切需要针对人类免疫缺陷病毒(HIV-1)的预防性和/或治疗性疫苗。诱导细胞免疫受到青睐,因为这些反应与HIV-1的控制相关。编码HIV-1 gag/pol和干扰素-γ(FPV gag/pol-IFNγ)的重组禽痘病毒(FPV)疫苗被推测可增强HIV特异性细胞免疫,并在先前感染HIV-1的猕猴中进行了进一步评估。开发了一种新的检测方法,用于检测HIV抗原刺激全血后IFNγ的分泌,以进一步评估FPV gag/pol-IFNγ疫苗的安全性和免疫原性。用FPV gag/pol-IFNγ免疫可安全地增强全血体外刺激后HIV特异性IFNγ的分泌,高于未共表达IFNγ的FPV gag/pol疫苗接种后的分泌水平。FPV gag/pol-IFNγ疫苗接种后,通过ELISPOT检测的HIV特异性IFNγ斑点形成细胞和CD4+淋巴细胞的CD69表达也均增强。因此,共表达IFNγ的FPV-HIV疫苗在猕猴中刺激了HIV特异性T细胞反应,应作为治疗性或预防性HIV疫苗进行进一步评估。

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