Potent monoclonal antibody-mediated neutralization of a divergent Hendra virus variant.

Publication Type:

Journal Article

Authors:

Wang, Zhaoqian; Dang, Ha V; Amaya, Moushimi; Xu, Yan; Yin, Randy; Yan, Lianying; Hickey, Andrew C; Annand, Edward J; Horsburgh, Bethany A; Reid, Peter A; Smith, Ina; Eden, John-Sebastian; Xu, Kai; Broder, Christopher C; Veesler, David

Source:

Proc Natl Acad Sci U S A, Volume 119, Issue 22, p.e2122769119 (2022)

Keywords:

Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Crystallography, X-Ray, Epitopes, Hendra Virus, Humans, Immunoglobulin Fab Fragments, Neutralization Tests, Post-Exposure Prophylaxis, Protein Domains, Viral Envelope Proteins

Abstract:

<p>SignificanceA new Hendra virus variant (HeV-g2) has been recently identified in two independent studies, increasing the concern of HeV spillover. Here, we show that HeV-g2 utilizes the same host receptor as HeV and that a panel of previously described HeV neutralizing antibodies cross-neutralizes HeV-g2 potently. Furthermore, we describe a monoclonal antibody (hAH1.3) neutralizing HeV and HeV-g2 and reveal its epitope using X-ray crystallography. We show that targeting four nonoverlapping epitopes on the HeV attachment protein simultaneously leads to potent HeV and HeV-g2 neutralization, supporting the development of a tetravalent monoclonal antibody cocktail. Collectively, our data provide a comprehensive assessment of available countermeasures against this newly described HeV-g2 variant and delineate multiple strategies for pandemic preparedness.</p>

PDB: 
7SYY, 7SYZ
Detector: 
PILATUS
EIGER2
Beamline: 
24-ID-C