1887

Abstract

The sequence H379–410 of the measles virus haemagglutinin (MV-H) protein forms a surface-exposed loop and contains three cysteine residues (Cys-381, Cys-386 and Cys-394) which are conserved among all measles isolates. It comprises the minimal sequential B cell epitope (BCE) (H386–400) of the neutralizing and protective MAb BH6 that neutralizes all wild-type viruses tested. The aim of this study was to design synthetic peptides which induce neutralizing antibodies against MV wild-type isolates. Peptides containing one or two copies of T cell epitopes (TCE) and BCEs of different lengths (H386–400, B; H379–400, B), in different combinations and orientations were produced and iteratively optimized for inducing neutralizing antibodies. Peptides with the shorter BCE induced sera that cross-reacted with MV but did not neutralize. The longer BCE containing the three cysteines (B) and two homologous TCE were required for neutralization activity. These sera neutralized wild-type strains of different clades and geographic origins. Neutralizing serum was also obtained after immunization with human promiscuous TCEs. Furthermore B-based peptides were fully immunogenic even in the presence of pre-existing MV-specific antibodies. The results suggest that subunit vaccines based on such peptides could potentially be used to actively protect infants against wild-type viruses irrespective of persisting maternal antibodies.

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2000-03-01
2024-03-28
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References

  1. Albrecht, P., Ennis, F. A., Saltzman, E. J. & Krugman, S. (1977). Persistence of maternal antibody in infants beyond 12 months: mechanism of measles vaccine failure. Journal of Pediatrics 91, 715-718.[CrossRef] [Google Scholar]
  2. Alkhatib, G. & Briedis, D. J. (1986). The predicted primary structure of the measles virus hemagglutinin. Virology 150, 479-490.[CrossRef] [Google Scholar]
  3. Benjamin, D. C., Berzofsky, J. A., East, I. J., Gurd, F. R., Hannum, C., Leach, S. J., Margoliash, E., Michael, J. G., Miller, A. & Prager, E. M. (1984). The antigenic structure of proteins: a reappraisal. Annual Review of Immunology 2, 67-101.[CrossRef] [Google Scholar]
  4. Demotz, S., Lanzavecchia, A., Eisel, U., Niemann, H., Widmann, C. & Corradin, G. (1989). Delineation of several DR-restricted tetanus toxin T cell epitopes. Journal of Immunology 142, 394-402. [Google Scholar]
  5. El Kasmi, K. C., Theisen, D., Brons, N. H. & Muller, C. P. (1998). The molecular basis of virus crossreactivity and neutralisation after immunisation with optimised chimeric peptides mimicking a putative helical epitope of the measles virus hemagglutinin protein. Molecular Immunology 35, 905-918.[CrossRef] [Google Scholar]
  6. El Kasmi, K. C., Theisen, D., Brons, N. H., Ammerlaan, W., Klingele, M., Truong, A. T. & Muller, C. P. (1999). A hemagglutinin-derived peptide-vaccine ignored by virus-neutralising passive antibodies, protects against murine measles encephalitis. Vaccine 17, 2436-2445.[CrossRef] [Google Scholar]
  7. Fournier, P., Brons, N. H. C., Berbers, G. A. M., Wiesmüller, K.-H., Fleckenstein, B. T., Schneider, F., Jung, G. & Muller, C. P. (1997). Antibodies to a new linear site at the topographical or functional interface between the haemagglutinin and fusion proteins protect against measles encephalitis. Journal of General Virology 78, 1295-1302. [Google Scholar]
  8. Giraudon, P. & Wild, T. F. (1985). Correlation between epitopes on hemagglutinin of measles virus and biological activities: passive protection by monoclonal antibodies is related to their hemagglutination inhibiting activity. Virology 144, 46-58.[CrossRef] [Google Scholar]
  9. Hu, A. & Norrby, E. (1994). Role of individual cysteine residues in the processing and antigenicity of the measles virus haemagglutinin protein. Journal of General Virology 75, 2173-2181.[CrossRef] [Google Scholar]
  10. Huiss, S., Damien, B., Schneider, F. & Muller, C. P. (1997). Characteristics of asymptomatic secondary immune responses to measles virus in late convalescent donors. Clinical Experimental Immunology 109, 416-420.[CrossRef] [Google Scholar]
  11. Levely, M. E., Mitchell, M. A. & Nicholas, J. A. (1990). Synthetic immunogens constructed from T-cell and B-cell stimulating peptides (T:B chimeras): preferential stimulation of unique T- and B-cell specificities is influenced by immunogen configuration. Cellular Immunology 125, 65-78.[CrossRef] [Google Scholar]
  12. Martineau, P., Leclerc, C. & Hofnung, M. (1996). Modulating the immunological properties of a linear B-cell epitope by insertion into permissive sites of the MalE protein. Molecular Immunology 33, 1345-1358.[CrossRef] [Google Scholar]
  13. Muller, C. P., Bunder, R., Mayser, H., Ammon, S., Weinmann, M., Brons, N. H., Schneider, F., Jung, G. & Wiesmuller, K. H. (1995a). Intramolecular immunodominance and intermolecular selection of H2d-restricted peptides define the same immunodominant region of the measles virus fusion protein. Molecular Immunology 32, 37-47.[CrossRef] [Google Scholar]
  14. Muller, C. P., Beauverger, P., Schneider, F., Jung, G. & Brons, N. H. C. (1995b). Cholera toxin B stimulates systemic neutralizing antibodies after intranasal co-immunization with measles virus. Journal of General Virology 76, 1371-1380.[CrossRef] [Google Scholar]
  15. Niewiesk, S. (1999). Cotton rats (Sigmodon hispidus): an animal model to study the pathogenesis of measles virus infection. Immunology Letters 65, 47-50.[CrossRef] [Google Scholar]
  16. Norrby, E. & Hammarskjold, B. (1972). Structural components of measles virus. Microbios 5, 17-29. [Google Scholar]
  17. Obeid, O. E., Partidos, C. D., Howard, C. R. & Steward, M. W. (1995). Protection against morbillivirus-induced encephalitis by immunisation with a rationally designed synthetic peptide vaccine containing B- and T-cell epitopes from the fusion protein of measles virus. Journal of Virology 69, 1420-1428. [Google Scholar]
  18. Partidos, C. D. & Steward, M. W. (1990). Prediction and identification of a T cell epitope in the fusion protein of measles virus immunodominant in mice and humans. Journal of General Virology 71, 2099-2105.[CrossRef] [Google Scholar]
  19. Partidos, C. D. & Steward, M. W. (1992). The effects of a flanking sequence on the immune response to a B and a T cell epitope from the fusion protein of measles virus. Journal of General Virology 73, 1987-1994.[CrossRef] [Google Scholar]
  20. Partidos, C. D., Ripley, J., Delmas, A., Obeid, O. E., Denbury, A. & Steward, M. W. (1997). Fine specificity of the antibody response to a synthetic peptide from the fusion protein and protection against measles virus-induced encephalitis in a mouse model. Journal of General Virology 78, 3227-3232. [Google Scholar]
  21. Rehe, G. T., Katona, I. M., Brunswick, M., Wahl, L. M., June, C. H. & Mond, J. J. (1990). Activation of human B lymphocytes by nanogram concentrations of anti-IgM-dextran conjugates. European Journal of Immunology 20, 1837-1842.[CrossRef] [Google Scholar]
  22. Sabin, A. B. (1992). My last will and testament on rapid elimination and ultimate global eradication of poliomyelitis and measles. Pediatrics 90, 162-169. [Google Scholar]
  23. Vacchio, M. S., Berzofsky, J. A., Krzych, U., Smith, J. A., Hodes, R. J. & Finnegan, A. (1989). Sequences outside a minimal immunodominant site exert negative effects on recognition by staphylococcal nuclease-specific T cell clones. Journal of Immunology 143, 2814-2819. [Google Scholar]
  24. Varsanyi, T. M., Utter, G. & Norrby, E. (1984). Purification, morphology and antigenic characterization of measles virus envelope components. Journal of General Virology 65, 355-366.[CrossRef] [Google Scholar]
  25. Wiesmüller, K.-H., Spahn, G., Handtmann, D., Schneider, F., Jung, G. & Muller, C. P. (1992). Heterogeneity of linear B cell epitopes of the measles virus fusion protein reacting with late convalescent sera. Journal of General Virology 73, 2211-2216.[CrossRef] [Google Scholar]
  26. World Health Report (1996).Fighting Disease, Fostering Development. Geneva, Switzerland: WHO.
  27. Wortis, H. H., Teutsch, M., Higer, M., Zheng, J. & Parker, D. C. (1995). B-cell activation by crosslinking of surface IgM or ligation of CD40 involves alternative signal pathways and results in different B-cell phenotypes. Proceedings of the National Academy of Sciences, USA 92, 3348-3352.[CrossRef] [Google Scholar]
  28. Ziegler, D., Fournier, P., Berbers, G. A. H., Steuer, H., Wiesmüller, K.-H., Fleckenstein, B., Schneider, F., Jung, G., King, C.-C. & Muller, C. P. (1996). Protection against measles virus encephalitis by monoclonal antibodies binding to a cystine loop domain of the H protein mimicked by peptides which are not recognized by maternal antibodies. Journal of General Virology 77, 2479-2489.[CrossRef] [Google Scholar]
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