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科学家开发出靶向血凝素锚定表位的广泛中和抗体
作者:小柯机器人 发布时间:2021/12/26 14:40:32

美国威尔·康奈尔医学Patrick C. Wilson等研究人员合作开发出靶向血凝素锚定表位的广泛中和抗体。这一研究成果于2021年12月23日在线发表在国际学术期刊《自然》上。

研究人员表示,针对流感病毒血凝素(HA)表位的广义中和抗体(bnAb)有可能对流感病毒感染提供几乎普遍的保护。然而,已经有报道可以逃避bnAb的病毒突变体。识别能够中和病毒逃逸突变体的bnAb类别对于通用流感病毒疫苗的设计至关重要。

研究人员报告了一类独特的bnAb,其靶标是HA柄结构的一个离散的膜近端锚定表位。锚状表位靶向抗体对H1病毒具有广泛的中和作用,并能与具有大流行威胁的H2和H5病毒发生交叉反应。靶向该锚定表位的抗体利用一个高度受限的组合,与融合肽中的保守残基进行广泛接触。此外,锚定表位靶向B细胞在人类记忆B细胞(MBC)库中很常见,并被水包油佐剂嵌合HA(cHA)疫苗捕获,这是一种潜在的通用流感病毒疫苗。为了最大限度地保护人们免受季节性和大流行性流感病毒的侵害,疫苗应促进这一先前未开发的、在人类MBC库中广泛存在的bnAb来源。

附:英文原文

Title: Broadly neutralizing antibodies target a hemagglutinin anchor epitope

Author: Guthmiller, Jenna J., Han, Julianna, Utset, Henry A., Li, Lei, Lan, Linda Yu-Ling, Henry, Carole, Stamper, Christopher T., McMahon, Meagan, ODell, George, Fernndez-Quintero, Monica L., Freyn, Alec W., Amanat, Fatima, Stovicek, Olivia, Gentles, Lauren, Richey, Sara T., de la Pea, Alba Torrents, Rosado, Victoria, Dugan, Haley L., Zheng, Nai-Ying, Tepora, Micah E., Bitar, Dalia J., Changrob, Siriruk, Strohmeier, Shirin, Huang, Min, Garca-Sastre, Adolfo, Liedl, Klaus R., Bloom, Jesse D., Nachbagauer, Raffael, Palese, Peter, Krammer, Florian, Coughlan, Lynda, Ward, Andrew B., Wilson, Patrick C.

Issue&Volume: 2021-12-23

Abstract: Broadly neutralizing antibodies (bnAbs) targeting epitopes of the influenza virus hemagglutinin (HA) have the potential to provide near universal protection against influenza virus infection1. However, viral mutants that escape bnAbs have been reported2,3. The identification of bnAb classes that can neutralize viral escape mutants is critical for universal influenza virus vaccine design. Here, we report a distinct class of bnAbs targeting a discrete membrane-proximal anchor epitope of the HA stalk domain. Anchor epitope-targeting antibodies are broadly neutralizing across H1 viruses and can cross-react with pandemic-threat H2 and H5 viruses. Antibodies targeting this anchor epitope utilize a highly restricted repertoire, which encodes for two public binding motifs that make extensive contacts with conserved residues in the fusion peptide. Moreover, anchor epitope-targeting B cells are common in the human memory B cell (MBC) repertoire and were recalled in humans by an oil-in-water adjuvanted chimeric HA (cHA) vaccine4,5, a potential universal influenza virus vaccine. To maximize protection against seasonal and pandemic influenza viruses, vaccines should aim to boost this previously untapped source of bnAbs that are widespread in the human MBC pool.

DOI: 10.1038/s41586-021-04356-8

Source: https://www.nature.com/articles/s41586-021-04356-8

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html