美国麻省理工学院Daniel Lingwood小组在研究中取得进展。他们报道了通过接种疫苗引起单个氨基酸的变化，可产生针对1组和2组甲型流感病毒的抗体保护。该项研究成果发表在2024年4月25日出版的《免疫》上。

课题组研究人员应用生发株结合的纳米颗粒免疫原，在人源化小鼠模型中从生理前体频率诱导出一类跨组保护性的广泛中和抗体。跨组保护依赖于B细胞库中人广泛中和抗体前体的存在，以及疫苗扩增抗体在CDRH2环中富集N55T替代，这是广泛中和抗体的标志。

在结构上，这种单一突变引入了一个灵活的支点来适应糖基化差异，并且可以单独实现跨组保护。因此，广泛的甲型流感病毒免疫可以通过最小的抗原输入，和非常简单的抗体开发途径从种系库中扩展出来。

研究人员表示，针对甲型流感病毒 (IAVs)的血凝素(HA)茎的广泛中和抗体(bnAbs)，往往对1组或2组病毒多样性有效。在更罕见的情况下，人体抗体抗原表位可以生成跨组保护性的双特异性抗体，这些抗体可以容纳1组和2组干细胞之间的保守聚糖差异。

附：英文原文

Title: Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses

Author: Rashmi Ray, Faez Amokrane Nait Mohamed, Daniel P. Maurer, Jiachen Huang, Berk A. Alpay, Larance Ronsard, Zhenfei Xie, Julianna Han, Monica Fernandez-Quintero, Quynh Anh Phan, Rebecca L. Ursin, Mya Vu, Kathrin H. Kirsch, Thavaleak Prum, Victoria C. Rosado, Thalia Bracamonte-Moreno, Vintus Okonkwo, Julia Bals, Caitlin McCarthy, Usha Nair, Masaru Kanekiyo, Andrew B. Ward, Aaron G. Schmidt, Facundo D. Batista, Daniel Lingwood

Issue&Volume: 2024-04-25

Abstract: Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.

DOI: 10.1016/j.immuni.2024.03.022

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00143-2