Probing neutralizing-antibody responses against emerging measles viruses (MVs): immune selection of MV by H protein-specific antibodies?
Measles virus (MV) infection and vaccination induce long-lasting immunity and neutralizing-antibody responses that are directed against the MV haemagglutinin (H) and the fusion (F) protein. A new MV genotype, D7, emerged recently in western Germany and rapidly replaced the long-term endemically circulating genotypes C2 and D6. Analysis of the H gene of C2, D6, D7 and vaccine viruses revealed uniform sequences for each genotype. Interestingly, a consistent exchange of seven distinct amino acids in the D7 H was observed when compared with residues shared between C2, D6 and vaccine viruses, and one exchange (D416-->N) in the D7 H was associated with an additional N-linked glycosylation. In contrast, the F gene is highly conserved between MVs of these genotypes. To test whether the D7 H protein escapes from antibody responses that were raised against earlier circulating or vaccine viruses, the neutralizing capacity of mAbs recognizing seven distinct domains on the H of an Edmonston-related MV was compared. The mAbs revealed a selective and complete loss of two neutralizing epitopes on the D7 H when compared with C2, D6 and vaccine viruses. To assess whether these alterations of the D7 H affect the neutralizing capacity of polyclonal B-cell responses, genotype-specific antisera were produced in cotton rats. However, no significant genotype-dependent difference was found. Likewise, human sera obtained from vaccinees (n=7) and convalescents (n=6) did not distinguish between the MV genotypes. Although the hypothesis of selection of D7 viruses by pre-existing neutralizing antibodies is compatible with the differing pattern of neutralizing epitopes on the H protein, it was not confirmed by the results of MV neutralization with polyclonal sera.
Santibanez
Sabine
S
WHO Measles/Rubella European RRL and NRC Measles, Mumps, Rubella, Robert Koch-Institut, Nordufer 20, D-13353 Berlin, Germany.
Niewiesk
Stefan
S
Institut für Virologie und Immunbiologie, University of Würzburg, Würzburg, Germany.
Heider
Alla
A
WHO Measles/Rubella European RRL and NRC Measles, Mumps, Rubella, Robert Koch-Institut, Nordufer 20, D-13353 Berlin, Germany.
Schneider-Schaulies
Jürgen
J
Institut für Virologie und Immunbiologie, University of Würzburg, Würzburg, Germany.
Berbers
Guy A M
GAM
Rijksinstituut voor Volksgezondheid en Milieu, Bilthoven, The Netherlands.
Zimmermann
Albert
A
WHO Measles/Rubella European RRL and NRC Measles, Mumps, Rubella, Robert Koch-Institut, Nordufer 20, D-13353 Berlin, Germany.
Halenius
Anne
A
WHO Measles/Rubella European RRL and NRC Measles, Mumps, Rubella, Robert Koch-Institut, Nordufer 20, D-13353 Berlin, Germany.
Wolbert
Anne
A
WHO Measles/Rubella European RRL and NRC Measles, Mumps, Rubella, Robert Koch-Institut, Nordufer 20, D-13353 Berlin, Germany.
Deitemeier
Ingrid
I
WHO Measles/Rubella European RRL and NRC Measles, Mumps, Rubella, Robert Koch-Institut, Nordufer 20, D-13353 Berlin, Germany.
Tischer
Annedore
A
WHO Measles/Rubella European RRL and NRC Measles, Mumps, Rubella, Robert Koch-Institut, Nordufer 20, D-13353 Berlin, Germany.
Hengel
Hartmut
H
WHO Measles/Rubella European RRL and NRC Measles, Mumps, Rubella, Robert Koch-Institut, Nordufer 20, D-13353 Berlin, Germany.
D000293:Adolescent; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003289:Convalescence; D005838:Genotype; D005858:Germany; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007223:Infant; D008457:Measles / Q000276:immunology*; D008458:Measles Vaccine / Q000276:immunology; D008459:Measles virus / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D009500:Neutralization Tests; D051381:Rats; D014611:Vaccination; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D007106:Immune Sera; D008458:Measles Vaccine; D014760:Viral Fusion Proteins; D014764:Viral Proteins