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. 2009 Jul 15;200(2):202-5.
doi: 10.1086/599794.

Development of resistance to passive therapy with a potently neutralizing humanized monoclonal antibody against West Nile virus

Shuliu Zhang  1 , Matthew R Vogt, Theodore Oliphant, Michael Engle, Evgeniy I Bovshik, Michael S Diamond, David W C Beasley
Affiliations

Development of resistance to passive therapy with a potently neutralizing humanized monoclonal antibody against West Nile virus

Shuliu Zhang et al. J Infect Dis. .

Abstract

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.

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Conflict of interest statement

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 have no conflicts of interest.

Figures

Figure 1
Figure 1
Neutralization by mAb hE16 of: (a) lineage 1 WNV strain NY99ic and K307R, T330I and T332A/K/M variants; (b) lineage 2 WNV strain SA58 and K332T variant; and (c) K307E escape variants selected in vivo from hE16-treated RAG mice. The data are an average of two to four independent experiments performed in triplicate on (a, b) Vero or (c) BHK21–15 cells.
See this image and copyright information in PMC

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