Low population serum microneutralization antibody titer against the predominating influenza A(H3N2) N121K virus during the severe influenza summer peak of Hong Kong in 2017

The 2017 Hong Kong influenza A(H3N2) summer season was unexpectedly severe. However, antigenic characterization of the 2017 circulating A(H3N2) viruses using ferret antisera did not show significant antigenic drift. We analyzed the hemagglutinin amino acid sequences of A(H3N2) virus circulating in Hong Kong in 2017, and found that viruses with hemagglutinin N121K substitution, which was rare before 2017, emerged rapidly and dominated in 2017 (52.4% of A[H3N2] virus in 2017 contains N121K substitution). Microneutralization assay using archived human sera collected from mid-2017 showed that the geometric mean microneutralization titer was 3.6-fold lower against a 2017 cell culture-grown circulating A(H3N2)-N121K virus (3391/2017 virus) than that against the cell culture-grown 2016–2017 A(H3N2) seasonal influenza vaccine-like vaccine virus (4801/2014 virus) (13.4 vs 41.8, P < 0.0001). Significantly fewer serum specimens had a microneutralization titer of 40 or above against 3391/2017 virus than that against 4801/2014 virus (26.4% vs 60.0%, P < 0.0001). Conversely, the geometric mean hemagglutination inhibition titer was slightly higher against 3391/2017 virus than that against the 4801/2014 virus (96.9 vs 55.4, P < 0.0001). Moreover, 59.1% of specimens had a significantly lower microneutralization antibody titer (≥4-fold) against 3391/2017 virus than that against 4801/2014 virus, but none for hemagglutination titer (P < 0.0001). Similar results of microneutralization and hemagglutination titers were observed for day 21-post-vaccination sera. Hence, the 2017 A(H3N2) summer peak in Hong Kong was associated with a low-microneutralization titer against the circulating virus. Our results support the use of microneutralization assay with human serum in assessing population susceptibility and antigenic changes of A(H3N2) virus. Novel and available immunization approach, such as topical imiquimod followed by intradermal vaccination, to broaden the neutralizing antibody response of influenza vaccine should be considered.