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 language | English (US) |
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Pages (from-to) | 237-246 |
Number of pages | 10 |
Journal | Virology |
Volume | 454-455 |
Issue number | 1 |
DOIs | |
State | Published - Apr 2014 |
Keywords
- Cancer
- Human serum
- Ligand display
- Measles virus
- Monoclonal antibodies
- Neutralization
- Oncolytic virotherapy
- Scfv
- Virus retargeting
ASJC Scopus subject areas
- Virology