@article{87e08f316225479b96bf54aa769ec2c3,
title = "Serotypic evolution of measles virus is constrained by multiple co-dominant B cell epitopes on its surface glycoproteins",
abstract = "After centuries of pestilence and decades of global vaccination, measles virus (MeV) genotypes capable of evading vaccine-induced immunity have not emerged. Here, by systematically building mutations into the hemagglutinin (H) glycoprotein of an attenuated measles virus strain and assaying for serum neutralization, we show that virus evolution is severely constrained by the existence of numerous co-dominant H glycoprotein antigenic sites, some critical for binding to the pathogenicity receptors SLAMF1 and nectin-4. We further demonstrate the existence in serum of protective neutralizing antibodies targeting co-dominant fusion (F) glycoprotein epitopes. Lack of a substantial reduction in serum neutralization of mutant measles viruses that retain even one of the co-dominant antigenic sites makes evolution of pathogenic measles viruses capable of escaping serum neutralization in vaccinated individuals extremely unlikely.",
keywords = "antibody escape, antigenic evolution, measles virus fusion, measles virus hemagglutinin",
author = "Mu{\~n}oz-Al{\'i}a, {Miguel {\'A}ngel} and Nace, {Rebecca A.} and Lianwen Zhang and Russell, {Stephen J.}",
note = "Funding Information: We sincerely thank Mark J. Federspiel, PhD, for mAb cl48; Patricia Devaux, PhD, for cl55; Ianko D. Iankov, MD, PhD, for mAb 20H6; Prof. Claude Muller, MD, for the remaining murine nAbs as well as discussions; Veronica von Messling, PhD, for the rabbit anti-F antibody for western blotting; Roberto Cattaneo, PhD, for Vero/dogSLAMtag, measles virus antigenome plasmids, and rabbit anti-MeV antibodies for Western blotting; Rik L. de Swart, PhD, for the Mel-JuSo cell lines, human serum samples, and antibodies C28-10-8 and F3-5; the Mayo Clinic Biobank for serum samples from the Minnesotan cohort; M. Cristine Charlesworth, PhD, and Benjamin J. Madden (Mayo Clinic Proteomics Core) for purification and mass spectrometry of soluble receptors-Fc; Zene Matzuda, MD, PhD, DSc, for the split luciferase plasmids; and Eugene Bah for assistance with the initial quantitative fusion assays and useful discussions. We also thank the Mayo Clinic Biosafety Committee and anonymous reviewers for critical reading of the manuscript and helpful discussions. This work was funded by grants from Al and Mary Agnes McQuinn and the Mayo Clinic . The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Funding Information: We sincerely thank Mark J. Federspiel, PhD, for mAb cl48; Patricia Devaux, PhD, for cl55; Ianko D. Iankov, MD, PhD, for mAb 20H6; Prof. Claude Muller, MD, for the remaining murine nAbs as well as discussions; Veronica von Messling, PhD, for the rabbit anti-F antibody for western blotting; Roberto Cattaneo, PhD, for Vero/dogSLAMtag, measles virus antigenome plasmids, and rabbit anti-MeV antibodies for Western blotting; Rik L. de Swart, PhD, for the Mel-JuSo cell lines, human serum samples, and antibodies C28-10-8 and F3-5; the Mayo Clinic Biobank for serum samples from the Minnesotan cohort; M. Cristine Charlesworth, PhD, and Benjamin J. Madden (Mayo Clinic Proteomics Core) for purification and mass spectrometry of soluble receptors-Fc; Zene Matzuda, MD, PhD, DSc, for the split luciferase plasmids; and Eugene Bah for assistance with the initial quantitative fusion assays and useful discussions. We also thank the Mayo Clinic Biosafety Committee and anonymous reviewers for critical reading of the manuscript and helpful discussions. This work was funded by grants from Al and Mary Agnes McQuinn and the Mayo Clinic. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Conceptualization, M.?.M.-A. and S.J.R.; methodology, M.?.M.-A. and S.J.R.; validation, M.?.M.-A. and S.J.R.; investigation: M.?.M.-A. R.A.N. and L.Z.; analysis, M.?.M.-A. and S.J.R.; resources, M.?.M.-A. and S.J.R.; writing, review, and editing, M.?.M.-A. and S.J.R.; funding acquisition, S.J.R.; approval of the final manuscript, all authors. M.?.M.-A. and S.J.R. are inventors in a patent application filed by the Mayo Clinic relating to the virus described in this report (WO2018212842A1) that has been out-licensed. S.J.R. is a founder and equity holder of Vyriad. We worked to ensure sex balance in the selection of non-human subjects. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = apr,
day = "20",
doi = "10.1016/j.xcrm.2021.100225",
language = "English (US)",
volume = "2",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "4",
}