title: Escape From Monoclonal Antibody Neutralization Affects Henipavirus Fitness In Vitro and In Vivo.
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.
authors.affiliation: Department of Pathology Institute for Human Infections and Immunity.
authors.forename: Viktoriya
authors.initials: V
authors.lastname: Borisevich
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Benhur
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hickey
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Blair
authors.initials: B
authors.lastname: DeBuysscher
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Broder
authors.affiliation: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.affiliation: 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.
authors.forename: Barry
authors.initials: B
authors.lastname: Rockx
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000276:immunology; D006224:Cricetinae; D005260:Female; D056084:Genetic Fitness; D045403:Henipavirus / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D045464:Henipavirus Infections / Q000276:immunology / Q000821:virology*; D006801:Humans; D008647:Mesocricetus; D051379:Mice; D009154:Mutation; D009500:Neutralization Tests
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral
keywords: henipavirus; monoclonal antibody; neutralization escape; neutralizing antibody