Speaker
Description
Background: Previous work from our group identified a tight bottleneck for influenza A virus (IAV) that restricts the transmission of genetic diversity. The impact of viral (subtype and strain) and host (age, vaccination status) factors on bottleneck size are unclear. The 2021/2022 H3N2 season was characterized by strains that were antigenically drifted and exhibited a high household secondary attack rate, reflective of elevated transmission intensity between individuals.
Methods: Nasal swabs were collected daily from IAV infected individuals in two case-ascertained household studies, FluTES (2017/2018 through 2019/2020 seasons) and RVTN (2021/2022). Viruses were sequenced in duplicate, and intrahost single nucleotide variants (iSNV) were identified at a 0.5% frequency threshold using a benchmarked pipeline with >99.99% specificity for mutations present in both replicates. Transmission pairs were defined based on co-residence, test date, and genetic distance. For each possible transmission pair, the bottleneck was estimated using a beta binomial model.
Results: We successfully sequenced specimens from 109 individuals across the four influenza seasons. There were 2 H1N1 transmission pairs in 2017/2018, 33 H3N2 and 1 H1N1 in 2018/2019, 22 H1N1 in 2019/2020, and 25 H3N2 and 0 H1N1 in 2021/2022. The transmission bottleneck was 2 virions (CI 2, 2) for H3N2 and 6 (CI 5, 6) for H1N1. The H3N2 bottleneck was 2 (CI 2, 2) over the 2017/2018 through 2019/2020 seasons and 2 (CI 2, 2) during the 2021/2022 season, when a higher secondary attack rate (50 vs. 20.1%) was observed. There were no differences in the estimated bottleneck based on donor or recipient age or vaccination status.
Conclusions: IAV is subject to a tight bottleneck during transmission, which limits the onward propagation of newly arising variants. Tight bottlenecks may be intrinsic to the transmission process, as host and viral factors we evaluated did not strongly impact its size.
