title: Antibody neutralization of retargeted measles viruses.
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.
authors.affiliation: Department of Molecular Medicine, 200 1st Street SW, Guggenheim Building 18, Mayo Clinic, Rochester, MN, USA. Electronic address: Lech.patrycja@mayo.edu.
authors.forename: Patrycja J
authors.initials: PJ
authors.lastname: Lech
authors.affiliation: 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.
authors.forename: Roland
authors.initials: R
authors.lastname: Pappoe
authors.affiliation: Department of Biomedical Sciences, Tottori University, Japan. Electronic address: taka@med.tottori-u.ac.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tobin
authors.forename: Peter L
authors.initials: PL
authors.lastname: Nara
authors.affiliation: Department of Molecular Medicine, 200 1st Street SW, Guggenheim Building 18, Mayo Clinic, Rochester, MN, USA. Electronic address: sjr@mayo.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D006389:Hemagglutinins, Viral / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D008457:Measles / Q000276:immunology; D008458:Measles Vaccine / Q000276:immunology; D018103:Morbillivirus / Q000235:genetics* / Q000276:immunology*; D009500:Neutralization Tests
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C104413:H protein, Dolphin morbillivirus; D006389:Hemagglutinins, Viral; D008458:Measles Vaccine
keywords: Cancer; Human serum; Ligand display; Measles virus; Monoclonal antibodies; Neutralization; Oncolytic virotherapy; Virus retargeting; scfv
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