Influenza vaccine effectiveness by A(H3N2) phylogenetic sub-cluster and prior vaccination history: 2016-17 and 2017-18 epidemics in Canada.

BACKGROUND: The influenza A(H3N2) vaccine was updated from clade 3C.3a in 2015-16 to a clade 3C.2a strain for both 2016-17 and 2017-18. Circulating 3C.2a viruses showed considerable diversity in the hemagglutinin glycoprotein and the egg-adapted vaccine strain also bore mutations, notably T160K loss-of-glycosylation. METHODS: Vaccine effectiveness (VE) in 2016-17 and 2017-18 was assessed by test-negative-design, explored by A(H3N2) phylogenetic sub-cluster and prior season's vaccination history. RESULTS: In 2016-17, A(H3N2) VE was 36%(95%CI=18-50%): comparable with (43%;95%CI=24-58%) or without (33%;95%CI=-16-64%) prior vaccination in 2015-16. In 2017-18,VE was 14%(95%CI=-8-31%):lower with (9%;95%CI=-18-30%) versus without (45%;95%CI=-7-71%) prior vaccination in 2016-17. CONCLUSIONS: Exploring VE by phylogenetic sub-cluster and prior vaccination history reveals informative heterogeneity, but requires enhanced sample-size. Pivotal mutations conferring loss-of-glycosylation, and repeat vaccination with unchanged antigen, may be associated with reduced VE.