Lin Ting-Hui, Lee Chang-Chun David, Fernández-Quintero Monica L, Ferguson James A, Han Julianna, Zhu Xueyong, Yu Wenli, Guthmiller Jenna J, Krammer Florian, Wilson Patrick C, Ward Andrew B, Wilson Ian A
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Nat Commun. 2025 Feb 2;16(1):1268. doi: 10.1038/s41467-025-56496-4.
H1N1 influenza viruses are responsible for both seasonal and pandemic influenza. The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnAbs elicited in natural infection and immunization to influenza virus hemagglutinin (HA) can provide insights for development of a universal influenza vaccine. Here, we structurally and biophysically characterize four antibodies that bind to a conserved region on the HA membrane-proximal region known as the anchor epitope. Despite some diversity in their V and V genes, the antibodies interact with the HA through germline-encoded residues in HCDR2 and LCDR3. Somatic mutations on HCDR3 also contribute hydrophobic interactions with the conserved HA epitope. This convergent binding mode provides extensive neutralization breadth against H1N1 viruses and suggests possible countermeasures against H1N1 viruses.
甲型H1N1流感病毒引发季节性流感和大流行性流感。这些病毒持续的抗原转变和漂移凸显了研发通用流感疫苗以引发广泛中和抗体（bnAbs）的迫切需求。对自然感染和流感病毒血凝素（HA）免疫中产生的bnAbs进行鉴定和表征可为通用流感疫苗的研发提供思路。在此，我们从结构和生物物理角度表征了四种与HA膜近端区域一个被称为锚定表位的保守区域结合的抗体。尽管它们的V和V基因存在一些差异，但这些抗体通过HCDR2和LCDR3中种系编码的残基与HA相互作用。HCDR3上的体细胞突变也有助于与保守的HA表位形成疏水相互作用。这种趋同的结合模式提供了针对甲型H1N1流感病毒的广泛中和广度，并提示了针对甲型H1N1流感病毒的可能对策。
