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

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article number109628
JournalCell Reports
Volume36
Issue number9
DOIs
StatePublished - Aug 31 2021

Keywords

  • B lymphocytes
  • Hendra virus
  • Nipah virus
  • antigen-antibody reactions
  • epitopes
  • henipavirus infections
  • monoclonal antibodies
  • therapy
  • viral antibodies

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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