Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 213, Issue 3, Pages 448-455Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiv449
Keywords
henipavirus; neutralizing antibody; monoclonal antibody; neutralization escape
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Funding
- Department of Pathology and Institute for Human Infections and Immunity, University of Texas Medical Branch
- Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH)
- NIH, Department of Health and Human Services [AI054715]
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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.
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