The hemagglutinin (HA) stem region is a major target of universal influenza vaccine efforts owing to the presence of highly conserved epitopes across multiple influenza A virus (IAV) strains and subtypes. To explore the potential impact of vaccine-induced immunity targeting the HA stem, we examined the fitness effects of viral escape from stem-binding broadly neutralizing antibodies (stem-bnAbs). Recombinant viruses containing each individual antibody escape substitution showed diminished replication compared to wild-type virus, indicating that stem-bnAb escape incurred fitness costs. A second-site mutation in the HA head domain (N129D; H1 numbering) reduced the fitness effects observed in primary cell cultures and likely enabled the selection of escape mutations. Functionally, this putative permissive mutation increased HA avidity for its receptor. These results suggest a mechanism of epistasis in IAV, wherein modulating the efficiency of attachment eases evolutionary constraints imposed by the requirement for membrane fusion. Taken together, the data indicate that viral escape from stem-bnAbs is costly but highlights the potential for epistatic interactions to enable evolution within the functionally constrained HA stem domain.

Objective: Seasonal influenza is a preventable disease that may cause high morbidity and mortality. In the USA, the 2020 influenza season overlapped with the first wave of coronavirus disease 2019 (COVID-19) pandemic. There is a dearth of research on understanding influenza vaccination uptake and attitudes towards the vaccine among marginalised communities in the USA. The aim of this study was to examine general knowledge, misconceptions about, and barriers to influenza vaccination and determine if flu education delivered via trusted messengers improved knowledge among Asian Americans. Design: Quantitative prospective pre- and post-test design. Setting: Asian American communities in Metro Detroit area, Hamtramck, and Kent County in Michigan. Method: The study started with a training event in which 26 community leaders were trained to become trusted messengers to disseminate flu education. A total of 260 Asian American participants subsequently completed pre- and post-education surveys. Results: Asian Americans in the study reported low flu vaccination rate (48.5%). Reasons varied but included access-related issues (e.g. no access and no insurance) and health literacy (did not know they needed it). After education by trusted messengers, the paired t tests measuring improvement between pre- and post-survey scores showed a significant improvement ( p < .05) for all of the knowledge items. Conclusion: Educational campaigns using targeted messages to address specific barriers and acknowledge individuals’ concerns regarding misconceptions while providing equitable vaccine access can be key for the successful implementation of vaccination programmes.