Background: Although ferret antisera used in influenza surveillance did not detect antigenic drift of A(H1N1)pdm09 viruses during 2015-16 season, low vaccine effectiveness was reported in adults. We investigated the immune basis of low responses to circulating A(H1N1)pdm09 viruses following vaccination.
Methods: Over 300 paired adult (18-49 yrs) pre and post-vaccination sera collected in 6 seasons (2010-11 to 2015-16) were analyzed by hemagglutination inhibition assays to evaluate the antibody responses to thirteen A(H1N1) viruses circulated from 1977 to 2016. Microneutralization and serum adsorption assays were used to verify 163K- and 223R-specificity of antibodies.
Results: Individual antibody profiles to A(H1N1) viruses revealed three priming patterns: USSR/77-, TW/86- or NC/99-priming. Over 20% of adults had reduced titers to cell-propagated circulating 6B.1 and 6B.2 A(H1N1)pdm09 viruses compared to the A/California/07/2009 vaccine virus X-179A. Significantly reduced antibody reactivity to circulating viruses bearing K163Q was only observed in USSR/77-primed cohort, whereas significantly lower reactivity caused by egg-adapted Q223R change was detected across all 3 cohorts.
Conclusion: Both 163K-specificity driven by immune priming and 223R-specificity from egg-adapted changes in the vaccine contributed to low responses to circulating A(H1N1)pdm09 viruses following vaccination. Our study highlights the need to incorporate human serology in influenza surveillance and vaccine strain selection.