کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6140446 | 1594251 | 2014 | 10 صفحه PDF | دانلود رایگان |
- We tested whether retargeted ligand-displaying MVs are resistant to Ab neutralization.
- MVs with HAALS mutations evade selected neutralizing mAbs targeting receptor-binding surface (RBS).
- Displayed ligands do not protect MV from Abs tested, nor from serum neutralization.
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.
Journal: Virology - Volumes 454â455, April 2014, Pages 237-246