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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.
Affiliation
  • Harshbarger WD; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Deming D; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Lockbaum GJ; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
  • Attatippaholkun N; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Kamkaew M; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Hou S; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
  • Somasundaran M; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
  • Wang JP; Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
  • Finberg RW; Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
  • Zhu QK; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Schiffer CA; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA. Celia.schiffer@umassmed.edu.
  • Marasco WA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. wayne_marasco@dfci.harvard.edu.
Nat Commun ; 12(1): 559, 2021 01 25.
Article in En | MEDLINE | ID: mdl-33495478
ABSTRACT
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 among VH3-30 derived 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 of VH3-30 antibodies and reveals that 3I14 represents a novel structural solution within the VH3-30 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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Influenza A virus / Hemagglutinin Glycoproteins, Influenza Virus / Antibodies, Neutralizing / Antibodies, Viral / Epitopes Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Influenza A virus / Hemagglutinin Glycoproteins, Influenza Virus / Antibodies, Neutralizing / Antibodies, Viral / Epitopes Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Document type: Article Affiliation country: