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- Title
Structural basis for a human broadly neutralizing influenza A hemagglutinin stem-specific antibody including H17/18 subtypes.
- Authors
Chen, Yulu; Wang, Fei; Yin, Liwei; Jiang, Haihai; Lu, Xishan; Bi, Yuhai; Zhang, Wei; Shi, Yi; Burioni, Roberto; Tong, Zhou; Song, Hao; Qi, Jianxun; Gao, George F.
- Abstract
Influenza infection continues are a persistent threat to public health. The identification and characterization of human broadly neutralizing antibodies can facilitate the development of antibody drugs and the design of universal influenza vaccines. Here, we present structural information for the human antibody PN-SIA28's heterosubtypic binding of hemagglutinin (HA) from circulating and emerging potential influenza A viruses (IAVs). Aside from group 1 and 2 conventional IAV HAs, PN-SIA28 also inhibits membrane fusion mediated by bat-origin H17 and H18 HAs. Crystallographic analyses of Fab alone or in complex with H1, H14, and H18 HA proteins reveal that PN-SIA28 binds to a highly conserved epitope in the fusion domain of different HAs, with the same CDRHs but different CDRLs for different HAs tested, distinguishing it from other structurally characterized anti-stem antibodies. The binding characteristics of PN-SIA28 provides information to support the design of increasingly potent engineered antibodies, antiviral drugs, and/or universal influenza vaccines. Influenza continues to represent a major threat to public health, and the development of monoclonal antibodies (mAbs) that provide broad protection remains a key avenue for therapeutic development. Here, the authors demonstrate the molecular basis of neutralization for a human bnAb (PN-SIA28) against both endemic influenza A and emerging pathogens such as bat H17 and H18 viruses.
- Subjects
INFLUENZA; HEMAGGLUTININ; MONOCLONAL antibodies; MEMBRANE fusion; DRUG design; INFLUENZA vaccines
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-35236-y