Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.
Nat Microbiol. 2016 May 23;1(6):16058. doi: 10.1038/nmicrobiol.2016.58.
Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses. Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014-2015. This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature.
流感病毒经常发生突变，因此需要不断更新疫苗病毒。为了建立可能补充当前疫苗株选择过程的实验方法，我们通过与人或雪貂恢复期血清孵育，从具有血凝素蛋白（包括抗原位点）球状头部随机突变的人 H1N1 和 H3N2 流感病毒文库中选择抗原变体。我们还从用恢复期血清处理的人源病毒和已针对人源流感病毒免疫的小鼠中选择抗原逃逸变体。我们对过去流感病毒的初步研究确定了与自然界中出现的变体具有相似抗原性的逃逸突变体，证实了我们方法的可行性。我们对当代人源流感病毒的研究在 2014-2015 年大流行之前确定了逃逸突变体。这种方法可能有助于预测潜在的抗原逃逸变体，并在它们在自然界中广泛传播之前选择未来的疫苗候选物。
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