Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains

• DOI: 10.1073/pnas.1712377114
• Publication Date: 2017-11-06T20:21:45Z
• Authors: Seth J. Zost; Kaela Parkhouse; Megan E. Gumina; Kangchon Kim; Sebastian Diaz Perez; Patrick C. Wilson; John J. Treanor; Andrea J. Sant; Sarah Cobey; Scott E. Hensley
• Keywords: 0303 health sciences; Glycosylation; Influenza A Virus, H3N2 Subtype; Ferrets; Hemagglutinin Glycoproteins, Influenza Virus; Biological Sciences; Antibodies, Viral; 3. Good health; 03 medical and health sciences; Immunogenicity, Vaccine; Influenza Vaccines; Neutralization Tests; Influenza, Human; Mutation; Animals; Humans; Antigens, Viral; Chickens; Ovum

Significance The majority of influenza vaccine antigens are prepared in chicken eggs. Human vaccine strains grown in eggs often possess adaptive mutations that increase viral attachment to chicken cells. Most of these adaptive mutations are in the hemagglutinin protein, which functions as a viral attachment factor. Here, we identify a hemagglutinin mutation in the current egg-adapted H3N2 vaccine strain that alters antigenicity. We show that ferrets and humans exposed to the current egg-adapted H3N2 vaccine strain produce antibodies that poorly neutralize H3N2 viruses that circulated during the 2016–2017 influenza season. These studies highlight the challenges associated with producing influenza vaccine antigens in eggs, while offering a potential explanation of why there was only moderate vaccine effectiveness during the 2016–2017 influenza season.