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. 1995 Mar;69(3):1420–1428. doi: 10.1128/jvi.69.3.1420-1428.1995

Protection against morbillivirus-induced encephalitis by immunization with a rationally designed synthetic peptide vaccine containing B- and T-cell epitopes from the fusion protein of measles virus.

O E Obeid 1, C D Partidos 1, C R Howard 1, M W Steward 1
PMCID: PMC188728  PMID: 7531779

Abstract

Synthetic peptides representing T- and B-cell epitopes from the fusion (F) protein of measles virus (MV) were tested for their ability to induce a protective immune response against intracerebral challenge with neuroadapted strains of MV and canine distemper virus (CDV) in mice. Of the panel of peptides tested, only a chimeric peptide consisting of two copies of a promiscuous T-cell epitope (representing residues 288 to 302 of MV F protein) synthesized at the amino terminus of a B-cell epitope (representing residues 404 to 414 of MV F protein) was able to induce a protective response against challenge with MV and CDV in inbred mice. The protective response induced by this peptide (TTB) was associated with a significant reduction in mortality, histological absence of acute encephalitis, and greatly reduced titers of virus in the brains of TTB-immune mice following challenge compared with the results for nonimmunized controls. A chimeric peptide comprising one copy of the T-cell epitope and one copy of the B-cell epitope (TB) did not induce a protective response. A comparison of the antibody responses induced by the two chimeras suggested that differences in protective efficacy following immunization may be a result of the higher affinity of the antibody induced by the TTB peptide than that of the antibody induced by the TB peptide. In addition, differences in the immunoglobulin G subclass of the antipeptide antibody responses were observed, and these may play a role in the differences in protection observed. These results indicate that appropriately designed synthetic peptides have potential as vaccines for the induction of cross-reactive protection against morbilliviruses.

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Selected References

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  1. Arnon R., Horwitz R. J. Synthetic peptides as vaccines. Curr Opin Immunol. 1992 Aug;4(4):449–453. doi: 10.1016/s0952-7915(06)80037-3. [DOI] [PubMed] [Google Scholar]
  2. Baldridge J. R., Buchmeier M. J. Mechanisms of antibody-mediated protection against lymphocytic choriomeningitis virus infection: mother-to-baby transfer of humoral protection. J Virol. 1992 Jul;66(7):4252–4257. doi: 10.1128/jvi.66.7.4252-4257.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barrett T., Clarke D. K., Evans S. A., Rima B. K. The nucleotide sequence of the gene encoding the F protein of canine distemper virus: a comparison of the deduced amino acid sequence with other paramyxoviruses. Virus Res. 1987 Nov;8(4):373–386. doi: 10.1016/0168-1702(87)90009-8. [DOI] [PubMed] [Google Scholar]
  4. Borras-Cuesta F., Petit-Camurdan A., Fedon Y. Engineering of immunogenic peptides by co-linear synthesis of determinants recognized by B and T cells. Eur J Immunol. 1987 Aug;17(8):1213–1215. doi: 10.1002/eji.1830170820. [DOI] [PubMed] [Google Scholar]
  5. Delgado V., McLaren D. J. Evidence for enhancement of IgG1 subclass expression in mice polyvaccinated with radiation-attenuated cercariae of Schistosoma mansoni and the role of this isotype in serum-transferred immunity. Parasite Immunol. 1990 Jan;12(1):15–32. doi: 10.1111/j.1365-3024.1990.tb00933.x. [DOI] [PubMed] [Google Scholar]
  6. Giraudon P., Wild T. F. Correlation between epitopes on hemagglutinin of measles virus and biological activities: passive protection by monoclonal antibodies is related to their hemagglutination inhibiting activity. Virology. 1985 Jul 15;144(1):46–58. doi: 10.1016/0042-6822(85)90303-4. [DOI] [PubMed] [Google Scholar]
  7. Giraudon P., Wild T. F. Monoclonal antibodies against measles virus. J Gen Virol. 1981 Jun;54(Pt 2):325–332. doi: 10.1099/0022-1317-54-2-325. [DOI] [PubMed] [Google Scholar]
  8. Good M. F., Maloy W. L., Lunde M. N., Margalit H., Cornette J. L., Smith G. L., Moss B., Miller L. H., Berzofsky J. A. Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protein. Science. 1987 Feb 27;235(4792):1059–1062. doi: 10.1126/science.2434994. [DOI] [PubMed] [Google Scholar]
  9. Liebert U. G., Linington C., ter Meulen V. Induction of autoimmune reactions to myelin basic protein in measles virus encephalitis in Lewis rats. J Neuroimmunol. 1988 Jan;17(2):103–118. doi: 10.1016/0165-5728(88)90018-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Liebert U. G., ter Meulen V. Virological aspects of measles virus-induced encephalomyelitis in Lewis and BN rats. J Gen Virol. 1987 Jun;68(Pt 6):1715–1722. doi: 10.1099/0022-1317-68-6-1715. [DOI] [PubMed] [Google Scholar]
  11. Malvoisin E., Wild F. Contribution of measles virus fusion protein in protective immunity: anti-F monoclonal antibodies neutralize virus infectivity and protect mice against challenge. J Virol. 1990 Oct;64(10):5160–5162. doi: 10.1128/jvi.64.10.5160-5162.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Milich D. R. Synthetic T and B cell recognition sites: implications for vaccine development. Adv Immunol. 1989;45:195–282. doi: 10.1016/s0065-2776(08)60694-x. [DOI] [PubMed] [Google Scholar]
  13. Mitchison N. A. The carrier effect in the secondary response to hapten-protein conjugates. II. Cellular cooperation. Eur J Immunol. 1971 Jan;1(1):18–27. doi: 10.1002/eji.1830010104. [DOI] [PubMed] [Google Scholar]
  14. Norrby E., Enders-Ruckle G., Meulen V. Differences in the appearance of antibodies to structural components of measles virus after immunization with inactivated and live virus. J Infect Dis. 1975 Sep;132(3):262–269. doi: 10.1093/infdis/132.3.262. [DOI] [PubMed] [Google Scholar]
  15. Partidos C. D., Stanley C. M., Steward M. W. Immune responses in mice following immunization with chimeric synthetic peptides representing B and T cell epitopes of measles virus proteins. J Gen Virol. 1991 Jun;72(Pt 6):1293–1299. doi: 10.1099/0022-1317-72-6-1293. [DOI] [PubMed] [Google Scholar]
  16. Partidos C. D., Steward M. W. Prediction and identification of a T cell epitope in the fusion protein of measles virus immunodominant in mice and humans. J Gen Virol. 1990 Sep;71(Pt 9):2099–2105. doi: 10.1099/0022-1317-71-9-2099. [DOI] [PubMed] [Google Scholar]
  17. Partidos C. D., Steward M. W. 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. J Gen Virol. 1992 Aug;73(Pt 8):1987–1994. doi: 10.1099/0022-1317-73-8-1987. [DOI] [PubMed] [Google Scholar]
  18. Partidos C., Stanley C., Steward M. The effect of orientation of epitopes on the immunogenicity of chimeric synthetic peptides representing measles virus protein sequences. Mol Immunol. 1992 May;29(5):651–658. doi: 10.1016/0161-5890(92)90202-9. [DOI] [PubMed] [Google Scholar]
  19. Partidos C., Stanley C., Steward M. The influence of orientation and number of copies of T and B cell epitopes on the specificity and affinity of antibodies induced by chimeric peptides. Eur J Immunol. 1992 Oct;22(10):2675–2680. doi: 10.1002/eji.1830221030. [DOI] [PubMed] [Google Scholar]
  20. Portner A., Scroggs R. A., Naeve C. W. The fusion glycoprotein of Sendai virus: sequence analysis of an epitope involved in fusion and virus neutralization. Virology. 1987 Apr;157(2):556–559. doi: 10.1016/0042-6822(87)90301-1. [DOI] [PubMed] [Google Scholar]
  21. Shaw D. M., Stanley C. M., Partidos C. D., Steward M. W. Influence of the T-helper epitope on the titre and affinity of antibodies to B-cell epitopes after co-immunization. Mol Immunol. 1993 Aug;30(11):961–968. doi: 10.1016/0161-5890(93)90121-q. [DOI] [PubMed] [Google Scholar]
  22. Steward M. W., Stanley C. M., Dimarchi R., Mulcahy G., Doel T. R. High-affinity antibody induced by immunization with a synthetic peptide is associated with protection of cattle against foot-and-mouth disease. Immunology. 1991 Jan;72(1):99–103. [PMC free article] [PubMed] [Google Scholar]
  23. Taylor J., Pincus S., Tartaglia J., Richardson C., Alkhatib G., Briedis D., Appel M., Norton E., Paoletti E. Vaccinia virus recombinants expressing either the measles virus fusion or hemagglutinin glycoprotein protect dogs against canine distemper virus challenge. J Virol. 1991 Aug;65(8):4263–4274. doi: 10.1128/jvi.65.8.4263-4274.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wild T. F., Bernard A., Spehner D., Villeval D., Drillien R. Vaccination of mice against canine distemper virus-induced encephalitis with vaccinia virus recombinants encoding measles or canine distemper virus antigens. Vaccine. 1993;11(4):438–444. doi: 10.1016/0264-410x(93)90285-6. [DOI] [PubMed] [Google Scholar]

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