“…We found that multiple pre-existing (3C.2a.1, 3C.2a.2, 3C.2a.3) and emerging (putative 3C.2a.3a and 3C.2a.4) variants co-circulated, contributing to the summer influenza epidemic. Similar to what we have found in our clade 3C.2a.3 viruses, influenza A(H3N2) variants carrying N121K and S144K have been reported in the Denmark, Finland, Israel, Sweden and the UK, in 2016/17 [ 2 - 4 , 10 ]. In the report from the UK, clade 3C.2a.3 was further grouped into cluster I (carrying I58V and S219Y) and cluster II (N122D and S262N) [ 4 ].…”
Section: Discussionsupporting
confidence: 89%
“…The 3C.2a variants were reported possibly related to lower 2016/17 influenza VE against A(H3N2), but clinical details and outcomes of patients remain unknown [ 1 , 2 , 11 ]. We found that characteristics and case fatality rates of patients infected with different clades were similar.…”
We report a summer influenza epidemic caused by co-circulation of multiple influenza A(H3N2) variants in clade 3C.2a. Compared with other clades, a putative clade 3C.2a.3a was more commonly isolated from severely ill patients; 3C.2a.4 was more commonly isolated in outbreak cases. Time from vaccination to illness onset was significantly shorter in severely ill patients infected with clade 3C.2a.3; characteristics and outcomes of patients infected with different clades were similar. No resistance to antiviral medications was found.
“…We found that multiple pre-existing (3C.2a.1, 3C.2a.2, 3C.2a.3) and emerging (putative 3C.2a.3a and 3C.2a.4) variants co-circulated, contributing to the summer influenza epidemic. Similar to what we have found in our clade 3C.2a.3 viruses, influenza A(H3N2) variants carrying N121K and S144K have been reported in the Denmark, Finland, Israel, Sweden and the UK, in 2016/17 [ 2 - 4 , 10 ]. In the report from the UK, clade 3C.2a.3 was further grouped into cluster I (carrying I58V and S219Y) and cluster II (N122D and S262N) [ 4 ].…”
Section: Discussionsupporting
confidence: 89%
“…The 3C.2a variants were reported possibly related to lower 2016/17 influenza VE against A(H3N2), but clinical details and outcomes of patients remain unknown [ 1 , 2 , 11 ]. We found that characteristics and case fatality rates of patients infected with different clades were similar.…”
We report a summer influenza epidemic caused by co-circulation of multiple influenza A(H3N2) variants in clade 3C.2a. Compared with other clades, a putative clade 3C.2a.3a was more commonly isolated from severely ill patients; 3C.2a.4 was more commonly isolated in outbreak cases. Time from vaccination to illness onset was significantly shorter in severely ill patients infected with clade 3C.2a.3; characteristics and outcomes of patients infected with different clades were similar. No resistance to antiviral medications was found.
“…Group III strains (16/91) circulated between January and June 2017. Group IV strains (22/91) circulated between September 2016 and March 2017 and were most closely related to the A(H3N2) strains identified during 2016–2017 influenza season from several countries in the northern hemisphere (A/Denmark/107/2016, A/Israel/B6014/2016, and A/London/15/2017) [ 29 – 31 ]. Interestingly, several novel A(H3N2) strains (4/91) circulating between January and April 2017 possessed sufficient residue variations in addition to what were previously described to warrant a separate cluster (group V).…”
Influenza virus evolves rapidly due to the accumulated genetic variations on the viral sequence. Unlike in North America and Europe, influenza season in the tropical Southeast Asia spans both the rainy and cool seasons. Thus, influenza epidemiology and viral evolution sometimes differ from other regions, which affect the ever-changing efficacy of the vaccine. To monitor the current circulating influenza viruses in this region, we determined the predominant influenza virus strains circulating in Thailand between January 2016 and June 2017 by screening 7,228 samples from patients with influenza-like illness. During this time, influenza A(H3N2) virus was the predominant influenza virus detected. We then phylogenetically compared the hemagglutinin (HA) gene from a subset of these A(H3N2) strains (n = 62) to the reference sequences and evaluated amino acid changes in the dominant antigenic epitopes on the HA protein structure. The divergence of the circulating A(H3N2) from the A/Hong Kong/4801/2014 vaccine strain formed five genetic groups (designated I to V) within the 3C.2a clade. Our results suggest a marked drift of the current circulating A(H3N2) strains in Thailand, which collectively contributed to the declining predicted vaccine effectiveness (VE) from 74% in 2016 down to 48% in 2017.
“…Amino acid sequence data were downloaded from Global Initiative on Sharing All Influenza Data (GISAID) EpiFlu database (Supplementary Table 1 ) HA amino acid substitution 2014–2015 ( n = 51) 2016 ( n = 13) 2017 a ( n = 189) N121K 0 (0%) 1 (7.7%) 99 (52.4%) T135K 0 (0%) 0 (0%) 55 (29.1%) S144K 0 (0%) 0 (0%) 37 (19.6%) a Up to 13 December 2017 Fig. 2 Phylogenetic trees showing the relationship between influenza A(H3N2) viruses from Hong Kong in 2017, other representative A(H3N2) viruses, and recommended A(H3N2) viruses for influenza vaccines 12 , 13 . The phylogenetic tree was constructed using the Maximum Likelihood method based on the Hasegawa–Kishino–Yano model.…”
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.
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