Pathogenic measles viruses cannot evolve to bypass vaccine-induced neutralizing antibodies

After centuries of pestilence and decades of global vaccination, measles serotypes capable of evading vaccine-induced immunity have not emerged. Here, by systematically building mutations into the H-glycoprotein of an attenuated measles strain and assaying for serum neutralization, we show that virus evolution is severely constrained by the existence of numerous codominant H-glycoprotein antigenic sites, some critical for binding to pathogenicity receptors SLAMF1 and Nectin-4. We further demonstrate the existence in serum of protective neutralizing antibodies targeting codominant F-glycoprotein epitopes. Calculations suggest that evolution of pathogenic measles viruses capable of escaping serum neutralization in vaccinated individuals is a near-zero probability scenario.