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

Abstract

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.

Figure 1

The time-scaled phylogenetic tree of HA gene from globally circulating influenza A subtype H3N2 strains, including WHO-recommended vaccine strains (indicated by green arrow). Different branch colours indicated strains location. The right colour ribbon indicates the year of sample collection.

Figure 2

Genetic proximity of selected potential vaccine (p-vac) and WHO-recommended vaccine strain with circulating strains from consecutive seasons. Mean genetic distance (p-distance) of vaccine and p-vac strains in each season are shown separately as Box-plot graph. The number of analyzed sequences from a season were denoted with (n).

Figure 3

Amino acid changes in epitope site of global hemagglutinin protein (HA) sequences. The red bar indicates the percent of changes compared with the WHO-recommended vaccine, while others indicate p-vac. The green down-arrow indicates the site where p-vac (any of the four) showed higher proximity with global strains than the vaccine. The purple up-arrow indicates the site where the vaccine showed higher proximity than all p-vac.

Figure 4

(A) 3D structure of hemagglutinin protein (HA) indicating diversifying epitope sites for Bangladeshi strain; (B) changes in host receptor binding affinity for alterations in the amino acid, at the positions of diversifying epitope sites.