Human antibodies that neutralize respiratory droplet transmissible H5N1 influenza viruses
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.
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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Brief Report Immunology

Human antibodies that neutralize respiratory droplet transmissible H5N1 influenza viruses

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 2

Experimentally determined binding affinities compared with in silico–predicted binding energies of VN/1203 HA variants for each EM density fitting orientation.

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Experimentally determined binding affinities compared with in silico–pre...
Tighter binding is indicated by a more negative binding energy (y axis). The mutants were divided into binder, those with EC50 less than 1 μg/ml, and nonbinders, those with EC50 values greater than 10 μg/ml. The predicted binding energies of the binders did not differ significantly from nonbinders in orientation A (NS). The predicted binding energies of the binders did differ significantly from the nonbinders in orientation B. **P value between 0.001 and 0.1. WT or native VN/1203 binding is indicated in green. The bounds of the boxes indicate the 75th (top) and 25th (bottom) percentiles; the central lines within the boxes indicate the average value; the whiskers extend to the furthest value that extends 1.5 times the distance between the first and third quartiles; data points outside the whiskers indicate outlying values beyond the ×1.5 distance.