Measles viruses of genotype H1 evade recognition by vaccine-induced neutralizing antibodies targeting the linear haemagglutinin noose epitope

Abstract

The linear haemagglutinin noose epitope (HNE; aa 379-410) is a protective B-cell epitope and considered to be highly conserved in both the vaccine and the wild-type measles virus (MeV) haemagglutinin (H) proteins. Vaccine virus-derived monoclonal antibodies (mAbs) BH6 and BH216, which target the HNE, neutralized MeVs of genotypes B3, C2, D4, D5, D6, D7 and D8, and the vaccine strain Edmonston Zagreb. In the case of genotype H1, only strain Berlin.DEU/ 44.01 was neutralized by these mAbs, whereas strains Shenyang.CHN/22.99 and Sofia.BGR/ 19.05 were not. The H gene sequences of these two strains showed an exchange of proline 397 (P397) to leucine (L397). Mutated H proteins, with P397 exchanged to L and vice versa, were compared with original H proteins by indirect fluorescence assay. H proteins exhibiting P397 but not those with L397 were recognized by BH6 and BH216. This indicates that L397 leads to the loss of the neutralizing HNE. In contrast, human sera obtained from vaccinees (n510) did not discriminate between genotype H1 variants P397 and L397. This concurs with the epidemiological observation that the live-attenuated vaccine protects against both H1 variants. Furthermore, we demonstrated that MeVs of genotype H1 also lack the neutralizing epitopes defined by the vaccine virus-induced mAbs BH15, BH125 and BH47. The loss of several neutralizing epitopes, as shown for H1 viruses currently circulating endemically in Asia, implies that epitope monitoring should be considered to be included in measles surveillance.

Measles incidence rate and a phylogenetic study of contemporary genotype H1 measles strains in China: is an improved measles vaccine needed?

“…Other investigators have also noted antigenic difference between vaccine strains and H1 genotype viruses; our data are consistent with a previous observation that some H1 MV isolates lacking neutralizing epitopes, could escape neutralization in the presence of monoclonal antibodies that bind the native epitope [34].…”

Functional and Structural Characterization of Neutralizing Epitopes of Measles Virus Hemagglutinin Protein

“…Consequently, based on these observations, there is no evidence to suggest that MV undergoes a major antigenic drift. Nevertheless, several studies have suggested that currently circulating MV strains show antigenic variations, which could potentially affect the efficacy of vaccination (4,(13)(14)(15)(16)(17). Many amino acid residues have been documented to constitute a portion of an epitope.…”

Molecular Characterization of Wild Type Measles Virus from Adult Patients in Northern China, 2014

“…30,42 We also showed that 36 of the 42 virus strains carried a P397L substitution in the HNE region, which was previously shown to cause the loss of recognition of some monoclonal antibodies directed against HNE. 43 However, this substitution did not influence the neutralization by serum from vaccinated individuals. 44 Interestingly, we showed that the 7 cysteine residues which were important for the antigenic characterization of H protein were highly conserved in all the wild type strains.…”