Antibody neutralization of retargeted measles viruses

作者：Lech Patrycja J^*; Pappoe Roland; Nakamura Takafumi; Russell Stephen J

来源：Virology, 2014, 454: 237-246.

DOI：10.1016/j.virol.2014.01.027

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

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.

• 出版日期2014-4