Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cell Rep. 2017 Sep 19;20(12):2935-2943. doi: 10.1016/j.celrep.2017.08.084.
Antibodies that target both group 1 and group 2 influenza A viruses are valuable for therapeutic and vaccine development, but only a few have been reported to date. Here, we describe a new V1-69 antibody 27F3 that broadly recognizes heterosubtypic hemagglutinins (HAs) from both group 1 and group 2 influenza A viruses. Structural characterization of 27F3 Fab with A/California/04/2009 (H1N1) hemagglutinin illustrates that 27F3 shares the key binding features observed in other V1-69 antibodies to the HA stem. Compared to other V1-69 antibodies, the 27F3 V domain interacts with the HA stem in a distinct orientation, which alters its epitope and may have influenced its breadth. The diverse rotations of V1-69 antibodies on the HA stem epitope highlight the different ways that this antibody family can evolve to broadly neutralize influenza A viruses. These results have important implications for understanding how to elicit broad antibody responses against influenza virus.
针对 1 型和 2 型流感 A 病毒的抗体对于治疗和疫苗开发非常有价值，但迄今为止仅报道了少数几种。在这里，我们描述了一种新的 V1-69 抗体 27F3，它可以广泛识别来自 1 型和 2 型流感 A 病毒的异源血凝素 (HA)。用 A/加利福尼亚/04/2009（H1N1）血凝素对 27F3 Fab 的结构特征进行了描述，表明 27F3 与其他 V1-69 抗体到 HA 茎的关键结合特征共享。与其他 V1-69 抗体相比，27F3 V 结构域以独特的取向与 HA 茎相互作用，这改变了其表位，可能影响了其广谱性。V1-69 抗体在 HA 茎表位上的多样化旋转突出了该抗体家族能够广泛中和流感 A 病毒的不同方式。这些结果对于理解如何引发针对流感病毒的广泛抗体反应具有重要意义。
