Antibodies against egg- and cell-grown influenza A(H3N2) viruses in adults hospitalized during the 2017-2018 season

Abstract

BackgroundThe 2017-2018 US influenza season was severe with low vaccine effectiveness. Circulating A(H3N2) viruses from multiple genetic groups were antigenically similar to cell-grown vaccine strains. However, most influenza vaccines are egg-propagated.MethodsSerum was collected shortly after illness onset from 15 PCR confirmed A(H3N2) infected cases and 15 uninfected (controls) hospitalized adults enrolled in an influenza vaccine effectiveness study.Geometric mean titers against egg- and cell-grown A/Hong Kong/4801/2014 A(H3N2) vaccine strains and representative circulating viruses (including A/Washington/16/2017) were determined by microneutralization (MN) assays. Independent effects of strain-specific titers on susceptibility were estimated by logistic regression.ResultsMN titers against egg-A/Hong Kong were significantly higher among those who were vaccinated (MN GMT: 173 vs 41; P = 0.01). However, antibody titers to cell-grown viruses were much lower in all individuals (P>0.05) regardless of vaccination. In unadjusted models, a 2-fold increase in MN titers against egg-A/Hong Kong was not significantly protective against infection (29% reduction; p=0.09), but a similar increase in cell-A/Washington titer (3C.2a2) was protective (60% reduction; p=0.02). A similar increase in egg-A/Hong Kong titer was not significantly associated with odds of infection when adjusting for MN titers against A/Washington (15% reduction; P=0.61). A 54% reduction of odds of infection was observed with a 2-fold increase in A/Washington (not significant; P=0.07), adjusted for egg-A/Hong Kong titer.ConclusionAlthough individuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain, antibody responses to cell-grown circulating viruses may not be sufficient to provide protection, likely due to egg-adaptation in the vaccine.

Middle-aged individuals may be in a perpetual state of H3N2 influenza virus susceptibility

“…Our findings might shed light on the relatively low effectiveness of 3c2.A H3N2-based vaccines over the past 3 years 17 – 19 . Low effectiveness of 3c2.A H3N2-based vaccines is partially due to the inherent difficulties of preparing egg-based 3c2.A H3N2 antigens 20 . 3c2.A H3N2 viruses cannot grow in fertilized chicken eggs without first acquiring an amino acid substitution that abrogates a key glycosylation site in HA antigenic site B, and this egg-adaptation can dramatically alter antigenicity 8 , 21 .…”