Serotypic evolution of measles virus is constrained by multiple co-dominant B cell epitopes on its surface glycoproteins

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.

Automated summary

This study demonstrates that the evolution of measles virus is severely constrained by the existence of multiple co-dominant antigenic sites on the H glycoprotein, some of which are critical for binding to pathogenicity receptors. Protective neutralizing antibodies targeting co-dominant epitopes on the F glycoprotein have been identified in serum. Mutant measles viruses retaining even one co-dominant antigenic site are unlikely to escape serum neutralization in vaccinated individuals.