Antibody neutralization of retargeted measles viruses

Patrycja J. Lech, Roland Pappoe, Takafumi Nakamura, Stephen J. Russell

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The measles virus (MV) vaccine lineage is a promising oncolytic but prior exposure to the measles vaccine or wild-type MV strains limits treatment utility due to the presence of anti-measles antibodies. MV entry can be redirected by displaying a polypeptide ligand on the Hemagglutinin (H) C-terminus. We hypothesized that retargeted MV would escape neutralization by monoclonal antibodies (mAbs) recognizing the H receptor-binding surface and be less susceptible to neutralization by human antisera. Using chimeric H proteins, with and without mutations that ablate MV receptor binding, we show that retargeted MVs escape mAbs that target the H receptor-binding surface by virtue of mutations that ablate infection via SLAM and CD46. However, C-terminally displayed domains do not mediate virus entry in the presence of human antibodies that bind to the underlying H domain. In conclusion, utility of retargeted oncolytic measles viruses does not extend to evasion of human serum neutralization.

Original languageEnglish (US)
Pages (from-to)237-246
Number of pages10
JournalVirology
Volume454-455
Issue number1
DOIs
StatePublished - Apr 2014

Keywords

  • Cancer
  • Human serum
  • Ligand display
  • Measles virus
  • Monoclonal antibodies
  • Neutralization
  • Oncolytic virotherapy
  • Scfv
  • Virus retargeting

ASJC Scopus subject areas

  • Virology

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