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

¹ National Reference Centre Measles, Mumps, Rubella, Division of Viral Infections (FG12), Robert Koch-Institute, Nordufer 20, 13353 Berlin, Germany
² Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain

Correspondence
Sabine Santibanez
santibanezs{at}rki.de

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 (n=10) 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.

The GenBank/EMBL/DDBJ accession numbers for the measles virus isolates sequenced in this study are FJ865561 [GenBank] , FJ865562 [GenBank] , GQ331933 [GenBank] , FJ869874 [GenBank] –FJ869876 [GenBank] , GQ121274 [GenBank] , FJ808736 [GenBank] –FJ808738 [GenBank] and GQ338160 [GenBank] (full details in Table 1).