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
Author Information
Viktoriya Borisevich: Department of Pathology Institute for Human Infections and Immunity.
Benhur Lee: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York.
Andrew Hickey: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland.
Blair DeBuysscher: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
Christopher C Broder: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland.
Heinz Feldmann: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
Barry Rockx: Department of Pathology Department of Microbiology and Immunology Institute for Human Infections and Immunity Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana Department of Rare and Emerging Viral Infections and Response, Center for Infectious Disease Control, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
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.
