TY - JOUR
T1 - Escape from monoclonal antibody neutralization affects henipavirus fitness in vitro and in vivo
AU - Borisevich, Viktoriya
AU - Lee, Benhur
AU - Hickey, Andrew
AU - Debuysscher, Blair
AU - Broder, Christopher C.
AU - Feldmann, Heinz
AU - Rockx, Barry
N1 - Publisher Copyright:
© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - henipavirus
KW - monoclonal antibody
KW - neutralization escape
KW - neutralizing antibody
UR - http://www.scopus.com/inward/record.url?scp=84960389039&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiv449
DO - 10.1093/infdis/jiv449
M3 - Article
C2 - 26357909
AN - SCOPUS:84960389039
SN - 0022-1899
VL - 213
SP - 448
EP - 455
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -