Nath Neerukonda Sabari, Vassell Russell, Weiss Carol D
Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
Vaccines (Basel). 2020 Jul 12;8(3):382. doi: 10.3390/vaccines8030382.
Influenza continues to be a public health threat despite the availability of annual vaccines. While vaccines are generally effective at inducing strain-specific immunity, they are sub-optimal or ineffective when drifted or novel pandemic strains arise due to sequence changes in the major surface glycoprotein hemagglutinin (HA). The discovery of a large number of antibodies targeting the highly conserved stem region of HAs that are capable of potently neutralizing a broad range of virus strains and subtypes suggests new ways to protect against influenza. The structural characterization of HA stem epitopes and broadly neutralizing antibody paratopes has enabled the design of novel proteins, mini-proteins, and peptides targeting the HA stem, thus providing a foundation for the design of new vaccines. In this narrative, we comprehensively review the current knowledge about stem-directed broadly neutralizing antibodies and the structural features contributing to virus neutralization.
尽管每年都有流感疫苗可用，但流感仍然是一种公共卫生威胁。虽然疫苗通常能有效诱导针对特定毒株的免疫力，但当主要表面糖蛋白血凝素（HA）因序列变化出现抗原漂移或新型大流行毒株时，疫苗的效果就会欠佳或无效。大量靶向HA高度保守茎区的抗体能够有效中和多种病毒毒株和亚型，这一发现为预防流感提供了新途径。HA茎区表位和广泛中和性抗体互补位的结构特征，使得针对HA茎区的新型蛋白质、微型蛋白质和肽得以设计，从而为新型疫苗的设计奠定了基础。在本综述中，我们全面回顾了目前关于靶向茎区的广泛中和性抗体以及有助于病毒中和的结构特征的知识。
