Cell-Adapted Mutations and Antigenic Diversity of Influenza B Viruses in Missouri, 2019–2020 Season

Abstract

Influenza B viruses (IBVs) are causing an increasing burden of morbidity and mortality, yet the prevalence of culture-adapted mutations in human seasonal IBVs are unclear. We collected 368 clinical samples from patients with influenza-like illness in Missouri during the 2019–2020 influenza season and recovered 146 influenza isolates including 38 IBV isolates. Of MDCK-CCL34, MDCK-Siat1, and humanized MDCK (hCK), hCK showed the highest virus recovery efficiency. All Missourian IBVs belonged to the Victoria V1A.3 lineage, all of which contained a three-amino acid deletion on the HA protein and were antigenically distant from the Victoria lineage IBV vaccine strain used during that season. By comparing genomic sequences of these IBVs in 31 paired samples, eight cell-adapted nonsynonymous mutations were identified, with the majority in the RNA polymerase. Analyses of IBV clinical sample–isolate pairs from public databases further showed that cell- and egg-adapted mutations occurred more widely in viral proteins, including the receptor and antibody binding sites on HA. Our study suggests that hCK is an effective platform for IBV isolation and that culture-adapted mutations may occur during IBV isolation. As culture-adapted mutations may affect subsequent virus studies and vaccine development, the knowledge from this study may help optimize strategies for influenza surveillance, vaccine strain selection, and vaccine development.

Seasonal influenza vaccine performance and the potential benefits of mRNA vaccines

“…However, it is also possible for mutations in viruses to occur during cell culture propagation, which has been demonstrated for A/H3N2 and B strains. 111 , 112 A literature analysis of the antigenic similarity of egg-propagated and cell culture-propagated influenza viruses to worldwide circulating viruses for influenza seasons 2008 to 2018 found high antigenic similarity between both cell culture- and egg-propagated viruses with circulating A/H1N1 strains and B/Yamagata strains. 113 However, from 2012 to 2018, a substantially higher proportion of circulating A/H3N2 and B/Victoria strains were antigenically similar to cell culture-propagated viruses than egg-propagated viruses.…”

MAIVeSS: streamlined selection of antigenically matched, high-yield viruses for seasonal influenza vaccine production

“…Both approaches may take up to 6 months as well as have limitations. Egg or cell adaptation can result in undesired antigenic changes due to additional mutations in HA and reassortment strategies do not always lead to substantial improvements in yield 8 – 11 . Therefore, identifying influenza vaccine viruses with high-yield phenotypes directly from sequences obtained from clinical samples would be ideal and could potentially accelerate vaccine production timelines.…”