Unique structural solution from a VH3-30 antibody targeting the hemagglutinin stem of influenza A viruses

Harshbarger, Wayne D.; Deming, Derrick; Lockbaum, Gordon J.; Attatippaholkun, Nattapol; Kamkaew, Maliwan; Hou, Shurong; Somasundaran, Mohan; Wang, Jennifer P.; Finberg, Robert W.; Zhu, Quan Karen; Schiffer, Celia A.; Marasco, Wayne A.

doi:10.1038/s41467-020-20879-6

Title: Unique structural solution from a V_H3-30 antibody targeting the hemagglutinin stem of influenza A viruses

Journal Article · Mon Jan 25 00:00:00 EST 2021 · Nature Communications

DOI:https://doi.org/10.1038/s41467-020-20879-6· OSTI ID:1816205

Harshbarger, Wayne D. ^[1]; Deming, Derrick ^[1]; Lockbaum, Gordon J. ^[2];

^[1]; Kamkaew, Maliwan ^[1];

^[2]; Somasundaran, Mohan ^[2];

^[3]; Finberg, Robert W. ^[3];

^[1];

^[2];

^[4]

Dana-Farber Cancer Institute, Boston, MA (United States). Dept. of Cancer Immunology and Virology
Univ. of Massachusetts, Worcester, MA (United States). Medical School. Dept. of Biochemistry and Molecular Pharmacology
Univ. of Massachusetts, Worcester, MA (United States). Medical School. Dept. of Medicine
Dana-Farber Cancer Institute, Boston, MA (United States). Dept. of Cancer Immunology and Virology; Harvard Medical School, Boston, MA (United States). Dept. of Medicine

Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely amongV_H3-30derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection ofV_H3-30 antibodies and reveals that 3I14 represents a novel structural solution within theV_H3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1816205

Journal Information:: Nature Communications, Vol. 12, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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