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Structure paper

TitleStructural basis for the broad antigenicity of the computationally optimized influenza hemagglutinin X6.
Journal, issue, pagesStructure, Vol. 32, Issue 8, Page 1079-11089.e6, Year 2024
Publish dateAug 8, 2024
AuthorsKaito A Nagashima / John V Dzimianski / Meng Yang / Jan Abendroth / Giuseppe A Sautto / Ted M Ross / Rebecca M DuBois / Thomas E Edwards / Jarrod J Mousa /
PubMed AbstractInfluenza causes significant morbidity and mortality. As an alternative approach to current seasonal vaccines, the computationally optimized broadly reactive antigen (COBRA) platform has been ...Influenza causes significant morbidity and mortality. As an alternative approach to current seasonal vaccines, the computationally optimized broadly reactive antigen (COBRA) platform has been previously applied to hemagglutinin (HA). This approach integrates wild-type HA sequences into a single immunogen to expand the breadth of accessible antibody epitopes. Adding to previous studies of H1, H3, and H5 COBRA HAs, we define the structural features of another H1 subtype COBRA, X6, that incorporates HA sequences from before and after the 2009 H1N1 influenza pandemic. We determined structures of this antigen alone and in complex with COBRA-specific as well as broadly reactive and functional antibodies, analyzing its antigenicity. We found that X6 possesses features representing both historic and recent H1 HA strains, enabling binding to both head- and stem-reactive antibodies. Overall, these data confirm the integrity of broadly reactive antibody epitopes of X6 and contribute to design efforts for a next-generation vaccine.
External linksStructure / PubMed:38810648 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.64 - 3.57 Å
Structure data

28833

8f38

EMDB-28833, PDB-8f38:
Cryo-EM structure of X6 COBRA (H1N1) hemagglutinin bound to CR6261 Fab
Method: EM (single particle) / Resolution: 2.64 Å

40046

8ghk

EMDB-40046, PDB-8ghk:
CryoEM structure of Influenza A virus A/Melbourner/1/1946 (H1N1) hemagglutinin bound to GS10-X6-BE4 Fab
Method: EM (single particle) / Resolution: 3.47 Å

43008

8v7o

EMDB-43008, PDB-8v7o:
Fab fragment of human mAb #58 in complex with computationally optimized broadly reactive H1 influenza hemagglutinin X6
Method: EM (single particle) / Resolution: 3.57 Å

PDB-8sj9:
Crystal structure of the H1 hemagglutinin COBRA X6
Method: X-RAY DIFFRACTION / Resolution: 3.25 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-HOH:
WATER

ChemComp-EDO:
1,2-ETHANEDIOL

ChemComp-GOL:
GLYCEROL

Source
  • homo sapiens (human)
  • synthetic construct (others)
  • influenza a virus
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / NIAID hemagglutinin stalk binding antibody / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / NIAID / hemagglutinin stalk binding antibody / hemagglutinin / receptor binding / virus entry / fusion / Complex / antibody

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