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

• Published in: Journal of general virology Vol. 86; no. 2; pp. 365 - 374
• Main Authors: Santibanez, Sabine, Niewiesk, Stefan, Heider, Alla, Schneider-Schaulies, Jurgen, Berbers, Guy A. M, Zimmermann, Albert, Halenius, Anne, Wolbert, Anne, Deitemeier, Ingrid, Tischer, Annedore, Hengel, Hartmut
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.02.2005; Society for General Microbiology
• Subjects: Adolescent; Adult; Animals; Antibodies, Viral - immunology; Biological and medical sciences; Child; Child, Preschool; Convalescence; Fundamental and applied biological sciences. Psychology; Genotype; Germany; Human viral diseases; Humans; Immune Sera - immunology; Infant; Infectious diseases; Measles - immunology; Measles Vaccine - immunology; Measles virus; Measles virus - genetics; Measles virus - immunology; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Neutralization Tests; Rats; Vaccination; Viral diseases; Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye; Viral Fusion Proteins - genetics; Viral Fusion Proteins - immunology; Viral Proteins - immunology; Virology; Germany; Infection; Microbiology; Viral disease; Emerging disease; Measles; Neutralizing antibody; Humoral immunity; Protein; Neutralization; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.80467-0

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. Present address: College of Veterinary Medicine, Ohio State University, Columbus, OH, USA. Present address: Institute for Virology, University of Düsseldorf, Düsseldorf, Germany.