MilliporeSigma
  • Cooperativity mediated by rationally selected combinations of human monoclonal antibodies targeting the henipavirus receptor binding protein.

Cooperativity mediated by rationally selected combinations of human monoclonal antibodies targeting the henipavirus receptor binding protein.

Cell reports (2021-09-02)
Michael P Doyle, Nurgun Kose, Viktoriya Borisevich, Elad Binshtein, Moushimi Amaya, Marcus Nagel, Edward J Annand, Erica Armstrong, Robin Bombardi, Jinhui Dong, Kevin L Schey, Christopher C Broder, Larry Zeitlin, Erin A Kuang, Zachary A Bornholdt, Brandyn R West, Thomas W Geisbert, Robert W Cross, James E Crowe
ABSTRACT

Hendra virus and Nipah virus (NiV), members of the Henipavirus (HNV) genus, are zoonotic paramyxoviruses known to cause severe disease across six mammalian orders, including humans. We isolated a panel of human monoclonal antibodies (mAbs) from the B cells of an individual with prior exposure to equine Hendra virus (HeV) vaccine, targeting distinct antigenic sites. The most potent class of cross-reactive antibodies achieves neutralization by blocking viral attachment to the host cell receptors ephrin-B2 and ephrin-B3, with a second class being enhanced by receptor binding. mAbs from both classes display synergistic activity in vitro. In a stringent hamster model of NiV Bangladesh (NiVB) infection, antibodies from both classes reduce morbidity and mortality and achieve synergistic protection in combination. These candidate mAbs might be suitable for use in a cocktail therapeutic approach to achieve synergistic potency and reduce the risk of virus escape.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Histopaque®-1077, sterile-filtered, density: 1.077 g/mL
Sigma-Aldrich
Ouabain octahydrate, ≥95% (HPLC), powder
Sigma-Aldrich
Cyclosporin A, from Tolypocladium inflatum, BioReagent, for molecular biology, ≥95%
Sigma-Aldrich
HT Media Supplement (50×) Hybri-Max, lyophilized powder, γ-irradiated, BioXtra, suitable for hybridoma
Sigma-Aldrich
HAT Media Supplement (50×) Hybri-Max, γ-irradiated, lyophilized powder, BioXtra, suitable for hybridoma
Sigma-Aldrich
Chk2 Inhibitor II hydrate, ≥98% (HPLC)