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来自马来西亚的跨中和 CRF01_AE 感染的血浆针对人类免疫缺陷病毒 1 包膜糖蛋白的 CD4 结合位点。

Cross-Neutralizing CRF01_AE-Infected Plasma from Malaysia Targets CD4-Binding Site of Human Immunodeficiency Virus Type-1 Envelope Glycoprotein.

机构信息

Department of Biological Sciences, Sunway University, Bandar Sunway, Malaysia.

Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

出版信息

AIDS Res Hum Retroviruses. 2022 Feb;38(2):162-172. doi: 10.1089/AID.2020.0299. Epub 2021 Jun 17.

Abstract

Human immunodeficiency virus type-1 (HIV-1) antigenic variation poses a great challenge for vaccine immunogen design to elicit broadly neutralizing antibodies (bNAbs). Over the last 10-15 years, great progress has been made to understand the conserved sites of sensitivity on HIV envelope glycoprotein spikes targeted by bNAbs. Plasma neutralization mapping and monoclonal antibody isolation efforts have revealed five major conserved epitope clusters. Most of this work has focused on subtype B and C-infected Caucasian or African donors. It is not clear if the same epitopes and epitope rank order preferences are also true in donors infected with different HIV-1 subtypes and with different racial backgrounds. To investigate this point, in this study we report the first attempt to profile the bNAb specificities of CRF01_AE-infected Malaysian plasmas. We first measured neutralization titers of 21 plasmas against a subtype A, B, and AE pseudovirus panel. This revealed that 14% (3 of 21) plasmas had cross-clade breadth. Focusing on the cross-neutralizing plasma P9, we used AE and JR-FL mutant pseudoviruses, gp120 monomer interference, and native polyacrylamide gel electrophoresis to better understand the neutralization specificity. P9 demonstrates CD4-binding-site specificity with trimer dependence and D368 independence.

摘要

人类免疫缺陷病毒 1 型(HIV-1)抗原变异性对疫苗免疫原设计提出了巨大挑战,难以诱导广泛中和抗体(bNAb)。在过去 10-15 年中,人们在理解 bNAb 靶向的 HIV 包膜糖蛋白刺突的保守敏感位点方面取得了重大进展。血浆中和映射和单克隆抗体分离工作揭示了五个主要的保守表位簇。这项工作大多集中在 B 亚型和 C 亚型感染的白种人和非洲供体上。尚不清楚相同的表位和表位排序偏好是否也适用于不同 HIV-1 亚型和不同种族背景感染的供体。为了研究这一点,在这项研究中,我们首次尝试分析 CRF01_AE 感染的马来西亚血浆中 bNAb 的特异性。我们首先测量了 21 种血浆对 A、B 和 AE 假病毒组的中和效价。这表明 14%(21 个中的 3 个)的血浆具有跨谱系广度。我们专注于交叉中和的血浆 P9,使用 AE 和 JR-FL 突变假病毒、gp120 单体干扰和天然聚丙烯酰胺凝胶电泳,以更好地了解中和特异性。P9 表现出 CD4 结合位点特异性,与三聚体依赖性和 D368 独立性无关。

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