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一种2型艾滋病毒DNA疫苗可诱导针对2型艾滋病毒和猴免疫缺陷病毒的交叉反应性免疫应答。

An HIV type 2 DNA vaccine induces cross-reactive immune responses against HIV type 2 and SIV.

作者信息

Agadjanyan M G, Trivedi N N, Kudchodkar S, Bennett M, Levine W, Lin A, Boyer J, Levy D, Ugen K E, Kim J J, Weiner D B

机构信息

Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6100, USA.

出版信息

AIDS Res Hum Retroviruses. 1997 Dec 10;13(18):1561-72. doi: 10.1089/aid.1997.13.1561.

Abstract

We have previously reported on the generation of specific functional immune responses after inoculation of animals with expression vectors encoding HIV-1 genes. This article provides the details of the first application of this new technology to induce immune responses against HIV-2. This virus is molecularly and serologically distinct from HIV-1 and is in fact more closely related to the simian immunodeficiency virus (SIV). Anti-HIV-2 and SIV antibodies were induced in mice of three different haplotypes following a single intramuscular inoculation with an HIV-2/ROD envelope glycoprotein expression vector (pcEnv-2). Boosting of animals with pcEnv-2 induced both anti-HIV-2 neutralizing antibodies and T cell-proliferative responses against HIV-2 and SIVmac proteins. We compared the humoral and cellular immune responses of mice injected with pcEnv-2 and then boosted with either the homologous DNA construct or a recombinant Env protein. Animals boosted with pcEnv-2 generated B and T cell immune responses as strong as those of mice boosted with recombinant gp140 protein in adjuvant. Finally, cellular immune responses were significantly increased with the coadministration of pcEnv-2 and a plasmid expressing interleukin 12. We therefore conclude that DNA plasmid inoculation induces cross-reactive anti-HIV-2 and anti-SIVmac immune responses in mice. This technology should be further investigated as a potential vaccine component for this human pathogen.

摘要

我们之前报道过,在用编码HIV-1基因的表达载体接种动物后可产生特定的功能性免疫反应。本文详细介绍了这项新技术首次应用于诱导针对HIV-2的免疫反应的情况。这种病毒在分子和血清学上与HIV-1不同,实际上与猿猴免疫缺陷病毒(SIV)关系更为密切。在用HIV-2/ROD包膜糖蛋白表达载体(pcEnv-2)进行单次肌肉注射后,三种不同单倍型的小鼠体内诱导出了抗HIV-2和抗SIV抗体。用pcEnv-2对动物进行加强免疫,诱导出了抗HIV-2中和抗体以及针对HIV-2和SIVmac蛋白的T细胞增殖反应。我们比较了注射pcEnv-2后再用同源DNA构建体或重组Env蛋白进行加强免疫的小鼠的体液免疫和细胞免疫反应。用pcEnv-2进行加强免疫的动物产生的B细胞和T细胞免疫反应与用佐剂中的重组gp140蛋白进行加强免疫的小鼠一样强烈。最后,pcEnv-2与表达白细胞介素12的质粒共同给药可显著增强细胞免疫反应。因此,我们得出结论,DNA质粒接种可在小鼠体内诱导出交叉反应性抗HIV-2和抗SIVmac免疫反应。作为这种人类病原体的潜在疫苗成分,这项技术应进一步研究。

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