Patrycja J Lech1, Roland Pappoe2, Takafumi Nakamura3, Gregory J Tobin, Peter L Nara, Stephen J Russell4. 1. Department of Molecular Medicine, 200 1st Street SW, Guggenheim Building 18, Mayo Clinic, Rochester, MN, USA. Electronic address: Lech.patrycja@mayo.edu. 2. Department of Molecular Medicine, 200 1st Street SW, Guggenheim Building 18, Mayo Clinic, Rochester, MN, USA; Buena Vista University, Storm Lake, IA, USA. Electronic address: PappRol@bvu.edu. 3. Department of Biomedical Sciences, Tottori University, Japan. Electronic address: taka@med.tottori-u.ac.jp. 4. Department of Molecular Medicine, 200 1st Street SW, Guggenheim Building 18, Mayo Clinic, Rochester, MN, USA. Electronic address: sjr@mayo.edu.
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.
The pecies">measles virus (n class="Species">MV) vacciical">ne liical">neage is a promising oical">ncolytic but prior exposure to the n class="Species">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.
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