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由HIV-1MN重组糖蛋白120疫苗增强的HIV-1MN重组糖蛋白160疫苗诱导的细胞免疫和体液免疫。美国国立过敏与传染病研究所艾滋病疫苗评估小组。

HIV-1MN recombinant glycoprotein 160 vaccine-induced cellular and humoral immunity boosted by HIV-1MN recombinant glycoprotein 120 vaccine. National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group.

作者信息

Gorse G J, Corey L, Patel G B, Mandava M, Hsieh R H, Matthews T J, Walker M C, McElrath M J, Berman P W, Eibl M M, Belshe R B

机构信息

St. Louis Department of Veterans Affairs, Medical Center, and Saint Louis University, School of Medicine, Missouri 63106, USA.

出版信息

AIDS Res Hum Retroviruses. 1999 Jan 20;15(2):115-32. doi: 10.1089/088922299311547.

Abstract

We evaluated prime-boost immunization with two recombinant envelope glycoprotein subunit vaccines (HIV-1MN recombinant gp160 vaccine in alum adjuvant [MN rgp160] and HIV-1MN recombinant gp120 vaccine in alum adjuvant [MN rgp120]) for safety and immunogenicity in healthy, HIV-1-uninfected adults. The rationale was to combine the helper T cell memory and binding antibody responses typically induced by rgp160 vaccines with the superior neutralizing antibody responses induced by rgp120 vaccines. In a double-blinded, controlled trial, volunteers were randomly assigned to receive MN rgp160 or adjuvant placebo, and a subset later received MN rgp120. The two vaccines were safe, but reactions to MN rgp160 and its adjuvant placebo exceeded those to MN rgp120. MN rgp160 induced IgG binding antibodies, including all IgG subclasses, to MN rgp160 in all vaccine recipients. HIV-1MN-neutralizing and anti-V3 MN peptide-binding antibodies were observed in a majority of volunteers after the fourth MN rgp160 immunization, but at lower levels compared with immunization with MN rgp120 in historical controls. HIV-1-binding, neutralizing, and fusion inhibition antibodies were boosted to the highest levels among MN rgp160 recipients after MN rgp120 booster injections. MN rgp120 boosting appeared to alter the distribution of MN rgp160 vaccine-induced, anti-MN rgp160 IgG subclass antibodies. MN rgp160 induced helper T cell memory, measured by lymphocyte proliferation, Thl and Th2 cytokine production, and skin testing. Strategies including both subunit vaccines may help maximize antibody and helper T cell memory responses to HIV-1 envelope glycoprotein.

摘要

我们评估了两种重组包膜糖蛋白亚单位疫苗(铝佐剂中的HIV-1MN重组gp160疫苗[MN rgp160]和铝佐剂中的HIV-1MN重组gp120疫苗[MN rgp120])在健康、未感染HIV-1的成年人中的初免-加强免疫接种的安全性和免疫原性。其基本原理是将通常由rgp160疫苗诱导的辅助性T细胞记忆和结合抗体反应与rgp120疫苗诱导的卓越中和抗体反应相结合。在一项双盲对照试验中,志愿者被随机分配接受MN rgp160或佐剂安慰剂,一部分志愿者随后接受MN rgp120。这两种疫苗是安全的,但MN rgp160及其佐剂安慰剂引起的反应超过了MN rgp120引起的反应。MN rgp160在所有疫苗接种者中诱导产生了针对MN rgp160的IgG结合抗体,包括所有IgG亚类。在第四次MN rgp160免疫接种后,大多数志愿者中观察到了HIV-1MN中和抗体和抗V3 MN肽结合抗体,但与历史对照中用MN rgp120免疫相比,水平较低。在MN rgp120加强注射后,MN rgp160接种者中的HIV-1结合、中和和融合抑制抗体被提升到最高水平。MN rgp120加强似乎改变了MN rgp160疫苗诱导的、抗MN rgp160 IgG亚类抗体的分布。MN rgp160通过淋巴细胞增殖、Th1和Th2细胞因子产生以及皮肤试验来测量,诱导了辅助性T细胞记忆。包括这两种亚单位疫苗的策略可能有助于使针对HIV-1包膜糖蛋白的抗体和辅助性T细胞记忆反应最大化。

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