TY - JOUR
T1 - Development of resistance to passive therapy with a potently neutralizing humanized monoclonal antibody against West Nile virus
AU - Zhang, Shuliu
AU - Vogt, Matthew R.
AU - Oliphant, Theodore
AU - Engle, Michael
AU - Bovshik, Evgeniy I.
AU - Diamond, Michael S.
AU - Beasley, David W.C.
N1 - Funding Information:
Received 17 December 2008; accepted 5 February 2009; electronically published 15 June 2009. Potential conflicts of interest: M.S.D. is a consultant for MacroGenics, Inc., which has licensed the E16 antibody from Washington University for potential clinical use. All other authors report no potential conflicts. Financial support: National Institute of Allergy and Infectious Diseases (grant R21 AI063468 to D.W.C.B. and grant U01-AI061373 and contract HHSN266200600013C to M.S.D.); Institute for Human Infections and Immunity at the University of Texas Medical Branch (to D.W.C.B.). a S.Z. and M.R.V. contributed equally to the study. Reprints or correspondence: Dr. David W. C. Beasley, Dept. of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX ([email protected]).
PY - 2009/7/15
Y1 - 2009/7/15
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/67650697066
UR - https://www.scopus.com/pages/publications/67650697066#tab=citedBy
U2 - 10.1086/599794
DO - 10.1086/599794
M3 - Article
C2 - 19527169
AN - SCOPUS:67650697066
SN - 0022-1899
VL - 200
SP - 202
EP - 205
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -