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Human antibodies that neutralize respiratory droplet transmissible H5N1 influenza viruses
Natalie J. Thornburg, … , Jens Meiler, James E. Crowe Jr.
Natalie J. Thornburg, … , Jens Meiler, James E. Crowe Jr.
Published September 3, 2013
Citation Information: J Clin Invest. 2013;123(10):4405-4409. https://doi.org/10.1172/JCI69377.
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Brief Report Immunology

Human antibodies that neutralize respiratory droplet transmissible H5N1 influenza viruses

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Abstract

Recent studies described the experimental adaptation of influenza H5 HAs that confers respiratory droplet transmission (rdt) to influenza virus in ferrets. Acquisition of the ability to transmit via aerosol may lead to the development of a highly pathogenic pandemic H5 virus. Vaccines are predicted to play an important role in H5N1 control should the virus become readily transmissible between humans. We obtained PBMCs from patients who received an A/Vietnam/1203/2004 H5N1 subunit vaccine. Human hybridomas were then generated and characterized. We identified antibodies that bound the HA head domain and recognized both WT and rdt H5 HAs. We used a combination of structural techniques to define a mechanism of antibody recognition of an H5 HA receptor–binding site that neutralized H5N1 influenza viruses and pseudoviruses carrying the HA rdt variants that have mutations near the receptor-binding site. Incorporation or retention of this critical antigenic site should be considered in the design of novel H5 HA immunogens to protect against mammalian-adapted H5N1 mutants.

Authors

Natalie J. Thornburg, David P. Nannemann, David L. Blum, Jessica A. Belser, Terrence M. Tumpey, Shyam Deshpande, Gloria A. Fritz, Gopal Sapparapu, Jens C. Krause, Jeong Hyun Lee, Andrew B. Ward, David E. Lee, Sheng Li, Katie L. Winarski, Benjamin W. Spiller, Jens Meiler, James E. Crowe Jr.

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Figure 1

DXMS mapping of H5.3 epitope on VN/1203.

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DXMS mapping of H5.3 epitope on VN/1203.
(A) Ribbon map showing the infl...
(A) Ribbon map showing the influence of H5.3 on deuterium exchange of VN/1203 HA head domain. The top row shows the sequence of monomeric VN/1203 HA head domain protein. The second, third, and fourth row show protein dynamic features at different on-exchange time points. Blue suggests the regions that exchange more slowly upon H5.3 Fab binding; red suggests the regions that exchange more quickly upon binding. (B) Peptides that contain residues in the putative epitope mapped onto VN/1203 HA. Green indicates rdt mutations. Orange indicates receptor-binding site. Blue indicates peptides within the head domain of VN/1203 HA with altered deuterium exchange upon binding H5.3, with specific residues labeled in white.
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