Beyond glycan barriers: non-cognate ligands and protein mimicry approaches to elicit broadly neutralizing antibodies for HIV-1.

IF 9 2区 医学 Q1 CELL BIOLOGY Journal of Biomedical Science Pub Date : 2024-08-21 DOI:10.1186/s12929-024-01073-y
Stephen Ian Walimbwa, Petr Maly, Leona Raskova Kafkova, Milan Raska
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Abstract

Human immunodeficiency virus type 1 (HIV-1) vaccine immunogens capable of inducing broadly neutralizing antibodies (bNAbs) remain obscure. HIV-1 evades immune responses through enormous diversity and hides its conserved vulnerable epitopes on the envelope glycoprotein (Env) by displaying an extensive immunodominant glycan shield. In elite HIV-1 viremic controllers, glycan-dependent bNAbs targeting conserved Env epitopes have been isolated and are utilized as vaccine design templates. However, immunological tolerance mechanisms limit the development of these antibodies in the general population. The well characterized bNAbs monoclonal variants frequently exhibit extensive levels of somatic hypermutation, a long third heavy chain complementary determining region, or a short third light chain complementarity determining region, and some exhibit poly-reactivity to autoantigens. This review elaborates on the obstacles to engaging and manipulating the Env glycoprotein as an effective immunogen and describes an alternative reverse vaccinology approach to develop a novel category of bNAb-epitope-derived non-cognate immunogens for HIV-1 vaccine design.

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超越糖屏障:非识别配体和蛋白质模拟方法诱导 HIV-1 广泛中和抗体。
能够诱导广泛中和抗体(bNAbs)的人类免疫缺陷病毒 1 型(HIV-1)疫苗免疫原仍不为人所知。HIV-1 通过巨大的多样性逃避免疫反应,并通过显示广泛的免疫显性聚糖屏蔽来隐藏其包膜糖蛋白(Env)上的保守脆弱表位。在精英 HIV-1 病毒携带者中,已经分离出针对保守 Env 表位的糖依赖性 bNAbs,并将其用作疫苗设计模板。然而,免疫耐受机制限制了这些抗体在普通人群中的发展。特征明显的 bNAbs 单克隆变体经常表现出大量的体细胞超突变、长的第三重链互补决定区或短的第三轻链互补决定区,有些还表现出对自身抗原的多反应性。这篇综述阐述了将 Env 糖蛋白作为有效免疫原并对其进行操作所面临的障碍,并介绍了一种可供选择的反向疫苗学方法,以开发一种新型的 bNAb 表位衍生非识别免疫原,用于 HIV-1 疫苗的设计。
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来源期刊
Journal of Biomedical Science
Journal of Biomedical Science 医学-医学:研究与实验
CiteScore
18.50
自引率
0.90%
发文量
95
审稿时长
1 months
期刊介绍: The Journal of Biomedical Science is an open access, peer-reviewed journal that focuses on fundamental and molecular aspects of basic medical sciences. It emphasizes molecular studies of biomedical problems and mechanisms. The National Science and Technology Council (NSTC), Taiwan supports the journal and covers the publication costs for accepted articles. The journal aims to provide an international platform for interdisciplinary discussions and contribute to the advancement of medicine. It benefits both readers and authors by accelerating the dissemination of research information and providing maximum access to scholarly communication. All articles published in the Journal of Biomedical Science are included in various databases such as Biological Abstracts, BIOSIS, CABI, CAS, Citebase, Current contents, DOAJ, Embase, EmBiology, and Global Health, among others.
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