Abstract
Egg-adaptive mutations in influenza hemagglutinin (HA) often emerge during the production of egg-based seasonal influenza vaccines, which contribute to the largest share in the global influenza vaccine market. While some egg-adaptive mutations have minimal impact on the HA antigenicity (e.g. G186V), others can alter it (e.g. L194P). Here, we show that the preference of egg-adaptive mutation in human H3N2 HA is strain-dependent. In particular, Thr160 and Asn190, which are found in many recent H3N2 strains, restrict the emergence of L194P but not G186V. Our results further suggest that natural amino acid variants at other HA residues also play a role in determining the preference of egg-adaptive mutation. Consistently, recent human H3N2 strains from different clades acquire different mutations during egg passaging. Overall, these results demonstrate that natural mutations in human H3N2 HA can influence the preference of egg-adaptation mutation, which has important implications in seed strain selection for egg-based influenza vaccine.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acids / genetics
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Animals
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Chickens
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Eggs
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Evolution, Molecular
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Hemagglutinin Glycoproteins, Influenza Virus
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Hemagglutinins
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Humans
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Influenza A Virus, H3N2 Subtype / genetics
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Influenza Vaccines* / genetics
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Influenza, Human*
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Mutation
Substances
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Amino Acids
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Hemagglutinin Glycoproteins, Influenza Virus
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Hemagglutinins
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Influenza Vaccines
Grants and funding
This work was supported by a fellowship from the Pasteur Foundation Asia (W.L.), the Calmette and Yersin scholarship from the Pasteur International Network Association (H.L.), the funding from Centre for Immunology & Infection, InnoHK, an initiative of the Innovation and Technology Commission, the Government of the Hong Kong SAR (R.B.), the startup fund from the University of Illinois at Urbana-Champaign (N.C.W.), the Health and Medical Research Fund (no.19180932) (C.K.P.M), the National Research Foundation of Korea (NRF) grant funded through the Korea government (NRF-2018M3A9H4055203) (C.K.P.M.), Guangdong-Hong Kong-Macau Joint Laboratory of Respiratory Infectious Disease (20191205) (C.K.P.M.) and the visiting scientist scheme from Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore (C.K.P.M.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.