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TitleIsolation of human antibodies against influenza B neuraminidase and mechanisms of protection at the airway interface.
Journal, issue, pagesImmunity, Vol. 57, Issue 6, Page 1413-11427.e9, Year 2024
Publish dateJun 11, 2024
AuthorsRachael M Wolters / James A Ferguson / Ivette A Nuñez / Elaine E Chen / Ty Sornberger / Luke Myers / Svearike Oeverdieck / Sai Sundar Rajan Raghavan / Chandrahaas Kona / Laura S Handal / Trevor E Esilu / Edgar Davidson / Benjamin J Doranz / Taylor B Engdahl / Nurgun Kose / Lauren E Williamson / C Buddy Creech / Katherine N Gibson-Corley / Andrew B Ward / James E Crowe /
PubMed AbstractInfluenza B viruses (IBVs) comprise a substantial portion of the circulating seasonal human influenza viruses. Here, we describe the isolation of human monoclonal antibodies (mAbs) that recognized ...Influenza B viruses (IBVs) comprise a substantial portion of the circulating seasonal human influenza viruses. Here, we describe the isolation of human monoclonal antibodies (mAbs) that recognized the IBV neuraminidase (NA) glycoprotein from an individual following seasonal vaccination. Competition-binding experiments suggested the antibodies recognized two major antigenic sites. One group, which included mAb FluB-393, broadly inhibited IBV NA sialidase activity, protected prophylactically in vivo, and bound to the lateral corner of NA. The second group contained an active site mAb, FluB-400, that broadly inhibited IBV NA sialidase activity and virus replication in vitro in primary human respiratory epithelial cell cultures and protected against IBV in vivo when administered systemically or intranasally. Overall, the findings described here shape our mechanistic understanding of the human immune response to the IBV NA glycoprotein through the demonstration of two mAb delivery routes for protection against IBV and the identification of potential IBV therapeutic candidates.
External linksImmunity / PubMed:38823390 / PubMed Central
MethodsEM (single particle)
Resolution2.89 - 3.36 Å
Structure data

41809

8u1c

EMDB-41809, PDB-8u1c:
A mechanistic understanding of protective influenza B neuraminidase mAbs at the airway interface
Method: EM (single particle) / Resolution: 2.89 Å

41824

8u1q

EMDB-41824, PDB-8u1q:
A mechanistic understanding of protective influenza B neuraminidase mAbs at the airway interface
Method: EM (single particle) / Resolution: 3.36 Å

41826

8u1s

EMDB-41826, PDB-8u1s:
A mechanistic understanding of protective influenza B neuraminidase mAbs at the airway interface
Method: EM (single particle) / Resolution: 3.21 Å

Chemicals

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

Source
  • homo sapiens (human)
  • influenza b virus (b/iowa/06/2017)
KeywordsHYDROLASE / Neuraminidase Sialidase

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