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.