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Broad neutralization of human immunodeficiency virus type 1 (HIV-1) elicited from human rhinoviruses that display the HIV-1 gp41 ELDKWA epitope.从展示HIV-1 gp41 ELDKWA表位的人鼻病毒中引发的对1型人类免疫缺陷病毒（HIV-1）的广泛中和作用。
J Virol. 2009 May;83(10):5087-100. doi: 10.1128/JVI.00184-09. Epub 2009 Mar 11.
2
Antigenic characteristics of rhinovirus chimeras designed in silico for enhanced presentation of HIV-1 gp41 epitopes [corrected].基于计算机设计增强 HIV-1 gp41 表位呈递的嵌合鼻病毒的抗原特性 [更正]。
J Mol Biol. 2010 Apr 2;397(3):752-66. doi: 10.1016/j.jmb.2010.01.064. Epub 2010 Feb 4.
3
In silico vaccine design based on molecular simulations of rhinovirus chimeras presenting HIV-1 gp41 epitopes.基于呈现HIV-1 gp41表位的鼻病毒嵌合体分子模拟的计算机疫苗设计。
J Mol Biol. 2009 Jan 16;385(2):675-91. doi: 10.1016/j.jmb.2008.10.089. Epub 2008 Nov 8.
4
ELNKWA-epitope specific antibodies induced by epitope-vaccine recognize ELDKWA- and other two neutralizing-resistant mutated epitopes on HIV-1 gp41.表位疫苗诱导产生的ELNKWA表位特异性抗体可识别HIV-1 gp41上的ELDKWA以及其他两个抗中和突变表位。
Immunol Lett. 2001 Jan 1;75(2):149-52. doi: 10.1016/s0165-2478(00)00298-4.
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Induction of high levels of antibodies recognizing the neutralizing epitope ELDKWA and the D- or K-position-mutated epitopes by candidate epitope vaccines against HIV-1.针对HIV-1的候选表位疫苗诱导产生高水平的可识别中和表位ELDKWA以及D或K位突变表位的抗体。
Int Arch Allergy Immunol. 2000 Aug;122(4):287-92. doi: 10.1159/000024411.
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Multiple antigen peptide mimetics containing gp41 membrane-proximal external region elicit broad neutralizing antibodies against human immunodeficiency virus type 1 in guinea pigs.含 gp41 膜近端外区的多种抗原肽模拟物在豚鼠中引发针对人类免疫缺陷病毒 1 的广泛中和抗体。
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Chimeric rhinoviruses displaying MPER epitopes elicit anti-HIV neutralizing responses.嵌合鼻病毒展示 MPER 表位可引发抗 HIV 中和反应。
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N-terminal residues of an HIV-1 gp41 membrane-proximal external region antigen influence broadly neutralizing 2F5-like antibodies.人类免疫缺陷病毒1型糖蛋白41膜近端外部区域抗原的N端残基影响广谱中和性2F5样抗体。
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Induction of HIV-1 broad neutralizing antibodies in 2F5 knock-in mice: selection against membrane proximal external region-associated autoreactivity limits T-dependent responses.2F5 基因敲入小鼠中 HIV-1 广谱中和抗体的诱导：针对膜近端外区相关自身反应性的选择限制了 T 依赖性反应。
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Multiepitope vaccines intensively increased levels of antibodies recognizing three neutralizing epitopes on human immunodeficiency virus-1 envelope protein.多表位疫苗显著提高了识别人类免疫缺陷病毒1型包膜蛋白上三个中和表位的抗体水平。
Scand J Immunol. 2000 May;51(5):497-501. doi: 10.1046/j.1365-3083.2000.00713.x.

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Front Immunol. 2022 Sep 8;13:871463. doi: 10.3389/fimmu.2022.871463. eCollection 2022.
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J Virol. 2016 Nov 28;90(24):10993-11006. doi: 10.1128/JVI.01403-16. Print 2016 Dec 15.
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mSphere. 2016 May 18;1(3). doi: 10.1128/mSphere.00086-16. eCollection 2016 May-Jun.
6
Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure.通过破坏六螺旋束结构来调节HIV-1 gp41膜近端外部区域的免疫原性特性。
Virology. 2016 Mar;490:17-26. doi: 10.1016/j.virol.2016.01.002. Epub 2016 Jan 21.
7
Virus-based nanoparticles as platform technologies for modern vaccines.基于病毒的纳米颗粒作为现代疫苗的平台技术。
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2016 Jul;8(4):554-78. doi: 10.1002/wnan.1383. Epub 2016 Jan 19.
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Immunogenic properties of a trimeric gp41-based immunogen containing an exposed membrane-proximal external region.一种包含暴露的膜近端外部区域的三聚体gp41免疫原的免疫原性特性。
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Emerging Vaccine Technologies.新兴疫苗技术
Vaccines (Basel). 2015 May 26;3(2):429-47. doi: 10.3390/vaccines3020429.
10
Human Rhinovirus Presenting 4E10 Epitope of HIV-1 MPER Elicits Neutralizing Antibodies in Human ICAM-1 Transgenic Mice.呈现HIV-1膜近端外部区域（MPER）4E10表位的人鼻病毒在人细胞间黏附分子-1（ICAM-1）转基因小鼠中引发中和抗体。
Mol Ther. 2015 Oct;23(10):1663-70. doi: 10.1038/mt.2015.107. Epub 2015 Jun 10.

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Lipid binding properties of 4E10, 2F5, and WR304 monoclonal antibodies that neutralize HIV-1.中和HIV-1的4E10、2F5和WR304单克隆抗体的脂质结合特性
Biochim Biophys Acta. 2009 Mar;1788(3):660-5. doi: 10.1016/j.bbamem.2008.11.015. Epub 2008 Dec 3.
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In silico vaccine design based on molecular simulations of rhinovirus chimeras presenting HIV-1 gp41 epitopes.基于呈现HIV-1 gp41表位的鼻病毒嵌合体分子模拟的计算机疫苗设计。
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Analysis of the human immunodeficiency virus type 1 gp41 membrane proximal external region arrayed on hepatitis B surface antigen particles.1型人类免疫缺陷病毒gp41膜近端外部区域排列在乙型肝炎表面抗原颗粒上的分析。
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从展示HIV-1 gp41 ELDKWA表位的人鼻病毒中引发的对1型人类免疫缺陷病毒（HIV-1）的广泛中和作用。

Broad neutralization of human immunodeficiency virus type 1 (HIV-1) elicited from human rhinoviruses that display the HIV-1 gp41 ELDKWA epitope.

作者信息

Arnold Gail Ferstandig, Velasco Paola K, Holmes Andrew K, Wrin Terri, Geisler Sheila C, Phung Pham, Tian Yu, Resnick Dawn A, Ma Xuejun, Mariano Thomas M, Petropoulos Christos J, Taylor John W, Katinger Hermann, Arnold Eddy

机构信息

Center for Advanced Biotechnology and Medicine, 679 Hoes Lane, Piscataway, NJ 08854-5638, USA.

出版信息

J Virol. 2009 May;83(10):5087-100. doi: 10.1128/JVI.00184-09. Epub 2009 Mar 11.

DOI:10.1128/JVI.00184-09
PMID:19279101
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2682058/
Abstract

In efforts to develop AIDS vaccine components, we generated combinatorial libraries of recombinant human rhinoviruses that display the well-conserved ELDKWA epitope of the membrane-proximal external region of human immunodeficiency virus type 1 (HIV-1) gp41. The broadly neutralizing human monoclonal antibody 2F5 was used to select for viruses whose ELDKWA conformations resemble those of HIV. Immunization of guinea pigs with different chimeras, some boosted with ELDKWA-based peptides, elicited antibodies capable of neutralizing HIV-1 pseudoviruses of diverse subtypes and coreceptor usages. These recombinant immunogens are the first reported that elicit broad, albeit modest, neutralization of HIV-1 using an ELDKWA-based epitope and are among the few reported that elicit broad neutralization directed against any recombinant HIV epitope, providing a critical advance in developing effective AIDS vaccine components.

摘要

为了开发艾滋病疫苗成分，我们构建了重组人鼻病毒组合文库，这些文库展示了人类免疫缺陷病毒1型（HIV-1）gp41膜近端外部区域高度保守的ELDKWA表位。使用具有广泛中和作用的人单克隆抗体2F5来筛选其ELDKWA构象类似于HIV构象的病毒。用不同的嵌合体免疫豚鼠，其中一些用基于ELDKWA的肽进行加强免疫，可诱导出能够中和多种亚型和共受体使用情况的HIV-1假病毒的抗体。这些重组免疫原是首次报道的使用基于ELDKWA的表位诱导对HIV-1产生广泛（尽管程度有限）中和作用的免疫原，也是少数报道的诱导针对任何重组HIV表位产生广泛中和作用的免疫原之一，为开发有效的艾滋病疫苗成分提供了关键进展。