Investigation of intrahost diversity by vaccine status and antibody titer

While influenza virus diversity and antigenic drift have been well characterized on a global scale, the factors that influence the virus’ rapid evolution within and between human hosts are less clear. Given the modest effectiveness of seasonal vaccination, vaccine-induced antibody responses could serve as a potent selective pressure for novel influenza variants at the individual or community level. We used next generation sequencing of patient-derived viruses from a randomized, placebo-controlled trial of vaccine efficacy to characterize the diversity influenza A virus and to define the impact of vaccine-induced immunity on within host populations. In our study population, we found that most intrahost single nucleotide variants were rare and that very few were shared by multiple individuals. Contrary to what has been suggested, we did not observe an association between either vaccination status or serological immunity on viral escape, the emergence of antigenic variants, or altered intrahost population diversity.

尽管流感病毒的多样性与抗原漂移（antigenic drift）已在全球范围内得到充分解析，但影响该病毒在人类宿主内部及宿主间快速演化的相关因素仍不甚明确。鉴于季节性疫苗接种的保护效力有限，疫苗诱导的抗体应答可在个体或社区层面成为新型流感变异株的强效选择压力。本研究借助一项疫苗效力随机安慰剂对照试验中获取的患者来源病毒的下一代测序（next generation sequencing）数据，对甲型流感病毒（Influenza A virus）的多样性进行解析，并明确疫苗诱导免疫对宿主内部病毒种群的影响。在本研究的受试人群中，我们发现绝大多数宿主内单核苷酸变异（intrahost single nucleotide variants）均为低频变异，仅有极少部分变异可在多个个体间共享。与此前的研究推测相悖，本研究未发现疫苗接种状态或血清学免疫与病毒逃逸、抗原变异株出现或宿主内种群多样性改变存在关联。