The evolutionary footprint of influenza A subtype H3N2 strains in Bangladesh: implication of vaccine strain selection.

In February each year, World Health Organization (WHO) recommends candidate vaccine viruses for the forthcoming northern hemisphere (NH) season; however, the influenza season in the temperate zone of NH begins in October. During egg- or cell culture-propagation, the vaccine viruses become too old to confer the highest match with the latest strains, impacting vaccine effectiveness. Therefore, an alternative strategy like mRNA-based vaccine using the most recent strains should be considered. We analyzed influenza A subtype H3N2 strains circulating in NH during the last 10 years (2009-2020). Phylogenetic analysis revealed multiple clades of influenza strains circulating every season, which had substantial mismatches with WHO-recommended vaccine strains. The clustering pattern suggests that influenza A subtype H3N2 strains are not fixed to the specific geographical region but circulate globally in the same season. By analyzing 39 seasons from eight NH countries with the highest vaccine coverage, we also provide evidence that the influenza A, subtype H3N2 strains from South and Southeast Asia, including Bangladesh, had the highest genetic proximity to the NH strains. Furthermore, insilico analysis showed minimal effect on the Bangladeshi HA protein structure, indicating the stability of Bangladeshi strains. Therefore, we propose that Bangladeshi influenza strains represent genetic makeup that may better fit and serve as the most suitable candidate vaccine viruses for the forthcoming NH season.