Differences in the Hemagglutinin Amino Acids of Japanese and US Influenza A/H3N2 Viral Isolates and their Relationship with Vaccine Strain Differences

Abstract

The effects of vaccination on the dynamics of influenza virus remain largely unknown. Different A/H3N2 vaccine strains were used in Japan and the United States (US) in the 2014-2015 season. To examine how different vaccine strains affect the selection of surviving variants, we compared hemagglutinin (HA) sequences in Japan with those in the US. A total of 85 A/H3N2 samples from 38 vaccinated and 47 unvaccinated Japanese patients (33 from the 2013-2014 and 52 from the 2014-2015 Japanese seasons) were isolated and genetically analyzed using a nextgeneration sequencer for comparison with 113 US isolates (30 from the 2013-2014 season and 83 from the 2014-2015 season) referenced from the GenBank database. HA1 amino acid (AA) differences between Japan and the US for the 2014-2015 vaccine strains were found at sites 128 (epitope B), 142 (A), 145 (A) and 198 (B). 145S and 198S in Japanese isolates, which matched with those of the 2014-2015 vaccine strain, significantly decreased between the two seasons, contrary to the full maintenance of US isolates (57.6% vs. 5.8% for 145S, P<0.0001; 100.0% vs. 75.0% for 198S, P=0.0012). The predominance of 128A and 142G was also lost in Japanese isolates, as observed while matching these AAs with those of the 2014-2015 vaccine strain (72.7% vs. 19.2% for 128A, P<0.0001; 75.8% vs. 15.4% for 142G, P<0.0001). Our data suggest that vaccine selection might be associated with the emergence of influenza variants genetically distant from vaccine strains.