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通过体内接种DNA在非人灵长类动物中诱导针对1型人类免疫缺陷病毒的体液免疫和细胞免疫反应。

Induction of humoral and cellular immune responses to the human immunodeficiency type 1 virus in nonhuman primates by in vivo DNA inoculation.

作者信息

Wang B, Boyer J, Srikantan V, Ugen K, Gilbert L, Phan C, Dang K, Merva M, Agadjanyan M G, Newman M

机构信息

Apollon, Inc., Malvern, Pennsylvania 19355, USA.

出版信息

Virology. 1995 Aug 1;211(1):102-12. doi: 10.1006/viro.1995.1383.

Abstract

DNA inoculation has the potential to produce antigens in a native as well as a host-"customized" form for presentation to the immune system. As such this technology may have relevance for vaccine/immune therapeutic strategies for a variety of infectious pathogens. In rodents in vivo inoculation of plasmid expression vectors encoding HIV-1 gene products leads to production of HIV-1 antigens in vivo, resulting in the production of both cellular and humoral immune responses. In primates only preliminary studies of serology have been reported. Here we report further evaluation of this new technology as a method to induce humoral and particularly cellular immune responses against a human pathogen, the HIV-1 virus, in nonhuman primates. Following inoculation and boosting of animals with an HIV gp160 plasmid expression vector we observed the induction of neutralizing responses against two diverse HIV-1 isolates in 2 of 3 vaccinated animals. T cell proliferative responses to HIV antigens were also observed in all plasmid-inoculated animals and specific cross-reactive cytotoxic T lymphocyte responses were developed in vaccinated animals. This report establishes the ability of DNA inoculation to induce cellular immune responses in nonhuman primates and suggests that further investigation of this technology with regard to human vaccine or immune therapeutic development is therefore warranted.

摘要

DNA接种有潜力以天然形式以及宿主“定制”形式产生抗原,以呈递给免疫系统。因此,这项技术可能与多种传染性病原体的疫苗/免疫治疗策略相关。在啮齿动物中,体内接种编码HIV-1基因产物的质粒表达载体可导致体内产生HIV-1抗原,从而产生细胞免疫和体液免疫反应。在灵长类动物中,仅报道了血清学的初步研究。在此,我们报告对这项新技术的进一步评估,该技术作为一种在非人灵长类动物中诱导针对人类病原体HIV-1病毒的体液免疫,特别是细胞免疫反应的方法。在用HIV gp160质粒表达载体对接种和加强免疫动物后,我们在3只接种疫苗的动物中的2只中观察到针对两种不同HIV-1分离株的中和反应的诱导。在所有接种质粒的动物中也观察到对HIV抗原的T细胞增殖反应,并且在接种疫苗的动物中产生了特异性交叉反应性细胞毒性T淋巴细胞反应。本报告证实了DNA接种在非人灵长类动物中诱导细胞免疫反应的能力,并表明因此有必要对该技术在人类疫苗或免疫治疗开发方面进行进一步研究。

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