Development of resistance to passive therapy with a potently neutralizing humanized monoclonal antibody against West Nile virus.
Previous studies have established the therapeutic efficacy of humanized E16 (hE16) monoclonal antibody against West Nile virus in animals. Here, we assess the potential for West Nile virus strains encoding mutations in the hE16 epitope to resist passive immunotherapy and for the selection of neutralization escape variants during hE16 treatment. Resistance to hE16 in vivo was less common than expected, because several mutations that affected neutralization in vitro did not significantly affect protection in mice. Moreover, the emergence of resistant variants after infection with fully sensitive virus occurred but was relatively rare, even in highly immunocompromised B and T cell-deficient RAG mice.
Zhang
Shuliu
S
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Vogt
Matthew R
MR
Oliphant
Theodore
T
Engle
Michael
M
Bovshik
Evgeniy I
EI
Diamond
Michael S
MS
Beasley
David W C
DW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D000939:Epitopes / Q000235:genetics; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D051379:Mice; D009154:Mutation; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism; D014901:West Nile Fever / Q000276:immunology / Q000628:therapy*; D014902:West Nile virus / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D000939:Epitopes; D014759:Viral Envelope Proteins