美国斯克里普斯研究所Ian A. Wilson团队取得最新进展。他们发现H3和H1流感病毒对HA茎抗体抵抗力的不同遗传障碍。2020年6月19日出版的《科学》杂志发表了这一成果。

使用集中于表位残基的深度突变扫描，他们发现，由于流感血凝素（HA）茎的结构差异，H3亚型对茎广泛中和的人抗体（bnAbs）抗性的遗传障碍较低，而H1亚型则显著较高。

在自然循环菌株中可以观察到H3中的几个强抗性突变，并且不会降低体外病毒适应性和体内致病性。这项研究突出了开发真正通用的流感疫苗的潜在挑战。

据悉，针对HA高度保守的茎干区域的bnAbs的发现和表征，已经为考虑通用流感疫苗做出了贡献。但是，还需要更彻底地评估对茎bnAb的抗性潜力。

附：英文原文

Title: Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses

Author: Nicholas C. Wu, Andrew J. Thompson, Juhye M. Lee, Wen Su, Britni M. Arlian, Jia Xie, Richard A. Lerner, Hui-Ling Yen, Jesse D. Bloom, Ian A. Wilson

Issue&Volume: 2020/06/19

Abstract: The discovery and characterization of broadly neutralizing human antibodies (bnAbs) to the highly conserved stem region of influenza hemagglutinin (HA) have contributed to considerations of a universal influenza vaccine. However, the potential for resistance to stem bnAbs also needs to be more thoroughly evaluated. Using deep mutational scanning, with a focus on epitope residues, we found that the genetic barrier to resistance to stem bnAbs is low for the H3 subtype but substantially higher for the H1 subtype owing to structural differences in the HA stem. Several strong resistance mutations in H3 can be observed in naturally circulating strains and do not reduce in vitro viral fitness and in vivo pathogenicity. This study highlights a potential challenge for development of a truly universal influenza vaccine.

DOI: 10.1126/science.aaz5143

Source: https://science.sciencemag.org/content/368/6497/1335