Deep sequencing reveals potential antigenic variants at low frequency in influenza A-infected human

Importance paragraph from the paper: "Influenza vaccines must be frequently reformulated due to the virus’s rapid evolution rate. We know that influenza viruses exist within each infected host as a “swarm” of genetically distinct viruses, but the role of this within-host diversity in the antigenic evolution of influenza has been unclear. We characterized here the genetic and potential antigenic diversity of influenza viruses infecting humans, some of whom became infected despite recent vaccination. Influenza virus between- and within-host genetic diversity was not significantly different in nonvaccinated and vaccinated humans, suggesting that vaccine-induced immunity does not exert strong selective pressure on viruses replicating in individual people. We found low-frequency mutations, below the detection threshold of traditional surveillance methods, in nonvaccinated and vaccinated humans that were recently associated with antibody escape. Interestingly, these potential antigenic variants did not reach fixation in infected people, suggesting that other evolutionary factors may be hindering their emergence in individual humans."

该论文的重要段落：由于流感病毒进化速度极快，流感疫苗必须频繁更新配方。已知每一名感染宿主体内的流感病毒均以由遗传特性各异的病毒构成的"集群"形式存在，但宿主内病毒多样性在流感抗原进化中所发挥的作用始终不明。本研究对感染人类的流感病毒的遗传多样性与潜在抗原多样性进行了表征，其中部分感染者即便在近期接种过疫苗后仍发生了感染。未接种疫苗者与接种疫苗者体内的流感病毒，其宿主间与宿主内遗传多样性均无显著差异，这表明疫苗诱导的免疫并未对个体体内复制的病毒施加强烈的选择压力。我们在未接种疫苗者与接种疫苗者体内发现了低频突变，这类突变的检出水平低于传统监测方法的检测阈值，且近期相关研究表明这类突变与抗体逃逸存在关联。值得注意的是，这些潜在的抗原变异株并未在感染者体内达到固定频率，这提示或许存在其他进化因素阻碍了这类变异株在个体宿主内的出现。