Glyco-engineered MDCK cells display preferred receptors of H3N2 influenza absent in eggs used for vaccines

• Published in: Nature communications Vol. 14; no. 1; pp. 6178 - 13
• Main Authors: Kikuchi, Chika, Antonopoulos, Aristotelis, Wang, Shengyang, Maemura, Tadashi, Karamanska, Rositsa, Lee, Chiara, Thompson, Andrew J., Dell, Anne, Kawaoka, Yoshihiro, Haslam, Stuart M., Paulson, James C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.10.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 101/58; 13/106; 13/109; 13/31; 631/326/596/1578; 631/45/1268; 631/45/221; 692/699/255/1578; 82/83; Animals; Binding; Cell lines; Dogs; Eggs; Evolution; Glycan; Hemagglutination; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins; Humanities and Social Sciences; Humans; Influenza; Influenza A Virus, H3N2 Subtype; Influenza Vaccines; Influenza, Human - prevention & control; Madin Darby Canine Kidney Cells; multidisciplinary; Polysaccharides - metabolism; Receptors; Science; Science (multidisciplinary); Vaccines; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-41908-0

Evolution of human H3N2 influenza viruses driven by immune selection has narrowed the receptor specificity of the hemagglutinin (HA) to a restricted subset of human-type (Neu5Acα2-6 Gal) glycan receptors that have extended poly-LacNAc (Galβ1-4GlcNAc) repeats. This altered specificity has presented challenges for hemagglutination assays, growth in laboratory hosts, and vaccine production in eggs. To assess the impact of extended glycan receptors on virus binding, infection, and growth, we have engineered N-glycan extended (NExt) cell lines by overexpressing β3-Ν-acetylglucosaminyltransferase 2 in MDCK, SIAT, and hCK cell lines. Of these, SIAT-NExt cells exhibit markedly increased binding of H3 HAs and susceptibility to infection by recent H3N2 virus strains, but without impacting final virus titers. Glycome analysis of these cell lines and allantoic and amniotic egg membranes provide insights into the importance of extended glycan receptors for growth of recent H3N2 viruses and relevance to their production for cell- and egg-based vaccines. Evolution of human H3N2 influenza has limited the specificity of hemagglutinin to a subset of glycan receptors, which brings challenges. By glyco-engineering cell lines, authors show the importance of extended glycan receptors for growth of recent H3N2 viruses and relevance to their production for vaccines.