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J Gen Virol 86 (2005), 365-374; DOI 10.1099/vir.0.80467-0

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© 2005 Society for General Microbiology

Probing neutralizing-antibody responses against emerging measles viruses (MVs): immune selection of MV by H protein-specific antibodies?

Sabine Santibanez1, Stefan Niewiesk2,{dagger}, Alla Heider1, Jürgen Schneider-Schaulies2, Guy A. M. Berbers3, Albert Zimmermann1,{ddagger}, Anne Halenius1, Anne Wolbert1, Ingrid Deitemeier1, Annedore Tischer1 and Hartmut Hengel1,{ddagger}

1 WHO Measles/Rubella European RRL and NRC Measles, Mumps, Rubella, Robert Koch-Institut, Nordufer 20, D-13353 Berlin, Germany
2 Institut für Virologie und Immunbiologie, University of Würzburg, Würzburg, Germany
3 Rijksinstituut voor Volksgezondheid en Milieu, Bilthoven, The Netherlands

Correspondence
Sabine Santibanez
SantibanezS{at}rki.de

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.

{dagger}Present address: College of Veterinary Medicine, Ohio State University, Columbus, OH, USA.

{ddagger}Present address: Institute for Virology, University of Düsseldorf, Düsseldorf, Germany.




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