2. Academic Validation
  3. Structure of an influenza group 2-neutralizing antibody targeting the hemagglutinin stem supersite

Structure of an influenza group 2-neutralizing antibody targeting the hemagglutinin stem supersite

  • Structure. 2022 Jul 7;30(7):993-1003.e6. doi: 10.1016/j.str.2022.04.003.
Crystal Sao-Fong Cheung 1,  Jason Gorman 1,  Sarah F Andrews 1,  Reda Rawi 1,  Mateo Reveiz 1,  Chen-Hsiang Shen 1,  Yiran Wang 1,  Darcy R Harris 1,  Alexandra F Nazzari 1,  Adam S Olia 1,  Julie Raab 1,  I-Ting Teng 1,  Raffaello Verardi 1,  Shuishu Wang 1,  Yongping Yang 1,  Gwo-Yu Chuang 1,  Adrian B McDermott 1,  Tongqing Zhou 1,  Peter D Kwong 2
Affiliations

Affiliations

  • 1 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • 2 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].
PMID: 35489332 DOI: 10.1016/j.str.2022.04.003
Abstract

Several influenza antibodies with broad group 2 neutralization have recently been isolated. Here, we analyze the structure, class, and binding of one of these antibodies from an H7N9 vaccine trial, 315-19-1D12. The cryo-EM structure of 315-19-1D12 Fab in complex with the hemagglutinin (HA) trimer revealed the antibody to recognize the helix A region of the HA stem, at the supersite of vulnerability recognized by group 1-specific and by cross-group-neutralizing antibodies. 315-19-1D12 was derived from HV1-2 and KV2-28 genes and appeared to form a new antibody class. Bioinformatic analysis indicated its group 2 neutralization specificity to be a consequence of four key residue positions. We specifically tested the impact of the group 1-specific N33 glycan, which decreased but did not abolish group 2 binding of 315-19-1D12. Overall, this study highlights the recognition of a broad group 2-neutralizing antibody, revealing unexpected diversity in neutralization specificity for antibodies that recognize the HA stem supersite.

Keywords

antibody class; hemagglutinin; influenza; neutralizing antibodies; stem supersite.

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