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Journal of General Virology header logo Journal of General Virology

Volume 106, Issue 7

Glycan site loss in two egg-adapted live attenuated influenza vaccine strains does not cause antigenic mismatches Open Access

Abstract

The haemagglutinin (HA) proteins of contemporary human H3N2 influenza viruses are heavily glycosylated. Glycans influence the protein’s receptor-binding properties and antigenic profile and can be lost when candidate influenza vaccine strains are propagated in embryonated chicken eggs. Glycan changes in egg-derived vaccine strains have been linked to reduced vaccine effectiveness in inactivated influenza vaccines due to changes in antigenicity, but this has not been investigated in live attenuated influenza vaccines (LAIVs). Here, we determined the impact of egg-adaptive glycosylation changes on the antigenicity of two H3N2 LAIV strains which lost an N-linked glycan site due to egg adaptation: A/New Caledonia/71/2014 (LAIV strain for the 2016–18 influenza seasons) and A/Kansas/14/2017 (LAIV strain for the 2019–20 influenza season). Glycosylation of these egg-adapted HA proteins, along with cell-adapted HA proteins from the same strains, was characterized using nano-liquid chromatography-MS, and their antigenic profiles were assessed with microneutralization assays. We found that the absent glycan sites in the egg-adapted strains were present and occupied by a glycan in the respective cell-adapted strains. Despite this, ferret sera raised against the egg-adapted A/New Caledonia/71/2014 strain were still able to effectively neutralize its glycosylated, cell-adapted counterpart and could also neutralize representatives of most circulating clades from 2016 to 2018. Sera raised against egg-adapted A/Kansas/71/2014 showed reduced cross-reactivity to its cell-adapted counterpart, but this effect was primarily driven by a separate egg adaptation, D190N, rather than the glycosylation change. These data show that glycan loss in LAIV HA proteins due to egg adaptation does not necessarily result in antigenic changes relative to cell-derived viruses.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): egg adaptation , glycosylation , influenza and live attenuated influenza vaccine (LAIV)
Funding
This study was supported by the:
  • AstraZeneca
    • Principal Award Recipient: NotApplicable
© 2025 AstraZeneca
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2025-07-03
2026-04-14

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Glycan site loss in two egg-adapted live attenuated influenza vaccine strains does not cause antigenic mismatches
J. Gen. Virol. 106, 002122 (2025); https://doi.org/10.1099/jgv.0.002122
/content/journal/jgv/10.1099/jgv.0.002122
/content/journal/jgv/10.1099/jgv.0.002122
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