5V2A

Crystal structure of Fab H7.167 in complex with influenza virus hemagglutinin from A/Shanghai/02/2013 (H7N9)

Replaces:  5F45

Summary for 5V2A

• Entry DOI: 10.2210/pdb5v2a/pdb
• Descriptor: Hemagglutinin, Light chain (kappa) of H7.167 antibody, Heavy chain of H7.167 antibody, ... (6 entities in total)
• Functional Keywords: hemagglutinin, receptor-binding site, human antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus (A/chicken/Henan/109/2013(H7N9)); More
• Total number of polymer chains: 4
• Total formula weight: 104929.01

Authors

Zhang, H.,Zhu, X.,Wilson, I.A. (deposition date: 2017-03-03, release date: 2017-04-05, Last modification date: 2023-10-04)

Primary citation

Thornburg, N.J.,Zhang, H.,Bangaru, S.,Sapparapu, G.,Kose, N.,Lampley, R.M.,Bombardi, R.G.,Yu, Y.,Graham, S.,Branchizio, A.,Yoder, S.M.,Rock, M.T.,Creech, C.B.,Edwards, K.M.,Lee, D.,Li, S.,Wilson, I.A.,Garcia-Sastre, A.,Albrecht, R.A.,Crowe, J.E.
H7N9 influenza virus neutralizing antibodies that possess few somatic mutations.
J. Clin. Invest., 126:1482-1494, 2016

PubMed Abstract: Avian H7N9 influenza viruses are group 2 influenza A viruses that have been identified as the etiologic agent for a current major outbreak that began in China in 2013 and may pose a pandemic threat. Here, we examined the human H7-reactive antibody response in 75 recipients of a monovalent inactivated A/Shanghai/02/2013 H7N9 vaccine. After 2 doses of vaccine, the majority of donors had memory B cells that secreted IgGs specific for H7 HA, with dominant responses against single HA subtypes, although frequencies of H7-reactive B cells ranged widely between donors. We isolated 12 naturally occurring mAbs with low half-maximal effective concentrations for binding, 5 of which possessed neutralizing and HA-inhibiting activities. The 5 neutralizing mAbs exhibited narrow breadth of reactivity with influenza H7 strains. Epitope-mapping studies using neutralization escape mutant analysis, deuterium exchange mass spectrometry, and x-ray crystallography revealed that these neutralizing mAbs bind near the receptor-binding pocket on HA. All 5 neutralizing mAbs possessed low numbers of somatic mutations, suggesting the clones arose from naive B cells. The most potent mAb, H7.167, was tested as a prophylactic treatment in a mouse intranasal virus challenge study, and systemic administration of the mAb markedly reduced viral lung titers.

PubMed: 26950424
DOI: 10.1172/JCI85317

Experimental method

X-RAY DIFFRACTION (4.656 Å)