Escape from monoclonal antibody neutralization affects henipavirus fitness in vitro and in vivo

Viktoriya Borisevich, Benhur Lee, Andrew Hickey, Blair Debuysscher, Christopher C. Broder, Heinz Feldmann, Barry Rockx

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Henipaviruses are zoonotic viruses that can cause severe and acute respiratory diseases and encephalitis in humans. To date, no vaccine or treatments are approved for human use. The presence of neutralizing antibodies is a strong correlate of protection against lethal disease in animals. However, since RNA viruses are prone to high mutation rates, the possibility that these viruses will escape neutralization remains a potential concern. In the present study, we generated neutralization-escape mutants, using 6 different monoclonal antibodies, and studied the effect of these neutralization-escape mutations on in vitro and in vivo fitness. These data provide a mechanism for overcoming neutralization escape by use of cocktails of cross-neutralizing monoclonal antibodies that recognize residues within the glycoprotein that are important for virus replication and virulence.

Original languageEnglish
Pages (from-to)448-455
Number of pages8
JournalJournal of Infectious Diseases
Volume213
Issue number3
DOIs
StatePublished - 1 Feb 2016

Keywords

  • henipavirus
  • monoclonal antibody
  • neutralization escape
  • neutralizing antibody

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