Anti–influenza H7 human antibody targets antigenic site in hemagglutinin head domain interface
Jinhui Dong, Iuliia Gilchuk, Sheng Li, Ryan Irving, Matthew T. Goff, Hannah L. Turner, Andrew B. Ward, Robert H. Carnahan, James E. Crowe Jr.
Jinhui Dong, Iuliia Gilchuk, Sheng Li, Ryan Irving, Matthew T. Goff, Hannah L. Turner, Andrew B. Ward, Robert H. Carnahan, James E. Crowe Jr.
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Concise Communication Immunology Infectious disease

Anti–influenza H7 human antibody targets antigenic site in hemagglutinin head domain interface

Abstract

Although broadly protective, stem-targeted Abs against the influenza A virus hemagglutinin (HA) have been well studied, very limited information is available on Abs that broadly recognize the head domain. We determined the crystal structure of the HA protein of the avian H7N9 influenza virus in complex with a pan-H7, non-neutralizing, protective human Ab. The structure revealed a B cell epitope in the HA head domain trimer interface (TI). This discovery of a second major protective TI epitope supports a model in which uncleaved HA trimers exist on the surface of infected cells in a highly dynamic state that exposes hidden HA head domain features.

Authors

Jinhui Dong, Iuliia Gilchuk, Sheng Li, Ryan Irving, Matthew T. Goff, Hannah L. Turner, Andrew B. Ward, Robert H. Carnahan, James E. Crowe Jr.

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Figure 2

Protective efficacy of H7-200 mAb in mice.

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Protective efficacy of H7-200 mAb in mice. Female BALB/c mice weighing 1...
Female BALB/c mice weighing 18–20 g were inoculated intraperitoneally with a 200-μg dose of H7-200 or a control Ab (DENV 2D22 as a negative control or rCR9114 as a positive control). Twenty-four hours after mAb treatment, anesthetized mice were inoculated intranasally with 104 focus-forming units of H7N9 SH13 (IDCDC-RG32A) virus in 50 μL sterile PBS. Mice were weighed and monitored daily for BW change and signs of disease for 14 days. Clinical scores were as follows: 1 = slight fur ruffling and/or back arching; 2 = extensive fur ruffling and hunched posture; 3 = minimal mobility, lethargy; 4 = found dead. Mice losing over 30% of their initial BW were euthanized humanely according to IACUC requirements. Data points indicate the mean values, and error bars indicate the SEM. n = 10 mice per group.