Yang Zhi-Yong, Wei Chih-Jen, Kong Wing-Pui, Wu Lan, Xu Ling, Smith David F, Nabel Gary J
Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Building 40, Room 4502, Mailstop Code MSC-3005, 40 Convent Drive, Bethesda, MD 20892, USA.
Science. 2007 Aug 10;317(5839):825-8. doi: 10.1126/science.1135165.
Influenza virus entry is mediated by the receptor binding domain (RBD) of its spike, the hemagglutinin (HA). Adaptation of avian viruses to humans is associated with HA specificity for alpha2,6- rather than alpha2,3-linked sialic acid (SA) receptors. Here, we define mutations in influenza A subtype H5N1 (avian) HA that alter its specificity for SA either by decreasing alpha2,3- or increasing alpha2,6-SA recognition. RBD mutants were used to develop vaccines and monoclonal antibodies that neutralized new variants. Structure-based modification of HA specificity can guide the development of preemptive vaccines and therapeutic monoclonal antibodies that can be evaluated before the emergence of human-adapted H5N1 strains.
流感病毒的进入是由其刺突蛋白血凝素(HA)的受体结合域(RBD)介导的。禽流感病毒对人类的适应性与HA对α2,6-连接而非α2,3-连接的唾液酸(SA)受体的特异性有关。在这里,我们确定了甲型H5N1(禽流感)HA中的突变,这些突变通过降低对α2,3-连接SA的识别或增加对α2,6-连接SA的识别来改变其对SA的特异性。利用RBD突变体开发了可中和新变体的疫苗和单克隆抗体。基于结构对HA特异性进行修饰可指导预防性疫苗和治疗性单克隆抗体的开发,这些疫苗和抗体可在适应人类的H5N1毒株出现之前进行评估。