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靶向 10E8 HIV-1 广谱中和抗体模拟表位的肌抑素支架变体，并在小鼠中引发 HIV-1 病毒中和血清。

Myomedin scaffold variants targeted to 10E8 HIV-1 broadly neutralizing antibody mimic gp41 epitope and elicit HIV-1 virus-neutralizing sera in mice.

机构信息

Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Vestec, Czech Republic.

Department of Immunology, Palacký University Olomouc, Olomouc, Czech Republic.

出版信息

Virulence. 2021 Dec;12(1):1271-1287. doi: 10.1080/21505594.2021.1920251.

DOI:10.1080/21505594.2021.1920251
PMID:33993840
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8128222/
Abstract

One of the proposed strategies for the development of a more efficient HIV-1 vaccine is based on the identification of proteins binding to a paratope of chosen broadly neutralizing antibody (bNAb) that will mimic cognate HIV-1 Env (glyco)protein epitope and could be used as potent immunogens for induction of protective virus-neutralizing antibodies in the immunized individuals. To verify this "non-cognate ligand" concept, we developed a highly complex combinatorial library designed on a scaffold of human myomesin-1 protein domain and selected proteins called Myomedins specifically binding to variable regions of HIV-1 broadly neutralizing antibody 10E8. Immunization of mice with these Myomedin variants elicited the production of HIV-1 Env-specific antibodies. Hyperimmune sera bound to Env pseudotyped viruses and weakly/moderately neutralized 54% of tested clade A, B, C, and AE pseudotyped viruses variants . These results demonstrate that Myomedin variants have the potential to mimic Env epitopes and could be used as potential HIV-1 vaccine components.

摘要

开发更有效的 HIV-1 疫苗的一种提出的策略基于鉴定与所选广泛中和抗体 (bNAb) 的结合表位的蛋白质，该蛋白质将模拟同源 HIV-1 Env（糖）蛋白表位，并可作为诱导免疫个体中保护性病毒中和抗体的有效免疫原。为了验证这一“非同源配体”概念，我们开发了一种高度复杂的组合文库，该文库设计在人肌联蛋白-1 蛋白结构域的支架上，并选择了专门与 HIV-1 广泛中和抗体 10E8 的可变区结合的蛋白质，称为肌联蛋白。用这些肌联蛋白变体免疫小鼠会引发 HIV-1 Env 特异性抗体的产生。高免疫血清与包膜假型病毒结合，并能轻微/中度中和 54% 的测试的 A、B、C 和 AE 包膜假型病毒变体。这些结果表明肌联蛋白变体有可能模拟 Env 表位，可作为潜在的 HIV-1 疫苗成分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/c466c3585e1a/KVIR_A_1920251_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/cecc2a94295f/KVIR_A_1920251_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/2c05724ee508/KVIR_A_1920251_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/2e5fa462be5b/KVIR_A_1920251_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/34d10d7b7f0e/KVIR_A_1920251_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/4e52d3cda9d8/KVIR_A_1920251_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/c466c3585e1a/KVIR_A_1920251_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/cecc2a94295f/KVIR_A_1920251_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/2c05724ee508/KVIR_A_1920251_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/2e5fa462be5b/KVIR_A_1920251_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/34d10d7b7f0e/KVIR_A_1920251_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/4e52d3cda9d8/KVIR_A_1920251_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd3/8128222/c466c3585e1a/KVIR_A_1920251_F0006_OC.jpg

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