RT Journal Article SR Electronic T1 An egg-derived sulfated N-Acetyllactosamine glycan is an antigenic decoy of influenza virus vaccines JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.16.435673 DO 10.1101/2021.03.16.435673 A1 Jenna J. Guthmiller A1 Henry A. Utset A1 Carole Henry A1 Lei Li A1 Nai-Ying Zheng A1 Weina Sun A1 Marcos Costa Vieira A1 Seth Zost A1 Min Huang A1 Scott E. Hensley A1 Sarah Cobey A1 Peter Palese A1 Patrick C. Wilson YR 2021 UL http://biorxiv.org/content/early/2021/03/16/2021.03.16.435673.abstract AB Influenza viruses grown in eggs for the purposes of vaccine generation often acquire mutations during egg adaptation or possess differential glycosylation patterns than viruses circulating amongst humans. Here, we report that seasonal influenza virus vaccines possess an egg-derived sulfated N-acetyllactosamine (LacNAc) that is an antigenic decoy. Half of subjects that received an egg-grown vaccine mounted an antibody response against this egg-derived antigen. Egg-binding monoclonal antibodies specifically bind viruses grown in eggs, but not viruses grown in other chicken derived cells, suggesting only egg-grown vaccines can induce anti-LacNAc antibodies. Notably, antibodies against the sulfated LacNAc utilized a restricted antibody repertoire and possessed features of natural antibodies, as most antibodies were IgM and have simple heavy chain complementarity determining region 3. By analyzing a public dataset of influenza virus vaccine induced plasmablasts, we discovered egg-binding public clonotypes that were shared across studies. Together, this study shows that egg-grown vaccines can induce antibodies against an egg-associated glycan, which may divert the host immune response away from protective epitopes.Competing Interest StatementThe authors have declared no competing interest.