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. 1997 Oct;71(10):7240–7245. doi: 10.1128/jvi.71.10.7240-7245.1997

Identification of an immunodominant neutralizing and protective epitope from measles virus fusion protein by using human sera from acute infection.

S F Atabani 1, O E Obeid 1, D Chargelegue 1, P Aaby 1, H Whittle 1, M W Steward 1
PMCID: PMC192064  PMID: 9311797

Abstract

Polyclonal sera obtained from African children with acute measles were used to screen a panel of 15-mer overlapping peptides representing the sequence of measles virus (MV) fusion (F) protein. An immunodominant antigenic region from the F protein (p32; amino acids 388 to 402) was found to represent an amino acid sequence within the highly conserved cysteine-rich domain of the F protein of paramyxoviruses. Epitope mapping of this peptide indicated that the complete 15-amino-acid sequence was necessary for high-affinity interaction with anti-MV antibodies. Immunization of two strains of mice with the p32 peptide indicated that it was immunogenic and could induce antipeptide antibodies which cross-reacted with and neutralized MV infectivity in vitro. Moreover, passive transfer of antipeptide antibodies conferred significant protection against fatal rodent-adapted MV-induced encephalitis in susceptible mice. These results indicate that this epitope represents a candidate for inclusion in a future peptide vaccine for measles.

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Selected References

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  1. Aaby P., Bukh J., Kronborg D., Lisse I. M., da Silva M. C. Delayed excess mortality after exposure to measles during the first six months of life. Am J Epidemiol. 1990 Aug;132(2):211–219. doi: 10.1093/oxfordjournals.aje.a115650. [DOI] [PubMed] [Google Scholar]
  2. Albrecht P., Herrmann K., Burns G. R. Role of virus strain in conventional and enhanced measles plaque neutralization test. J Virol Methods. 1981 Dec;3(5):251–260. doi: 10.1016/0166-0934(81)90062-8. [DOI] [PubMed] [Google Scholar]
  3. Buckland R., Gerald C., Barker R., Wild T. F. Fusion glycoprotein of measles virus: nucleotide sequence of the gene and comparison with other paramyxoviruses. J Gen Virol. 1987 Jun;68(Pt 6):1695–1703. doi: 10.1099/0022-1317-68-6-1695. [DOI] [PubMed] [Google Scholar]
  4. Choppin P. W., Richardson C. D., Merz D. C., Hall W. W., Scheid A. The functions and inhibition of the membrane glycoproteins of paramyxoviruses and myxoviruses and the role of the measles virus M protein in subacute sclerosing panencephalitis. J Infect Dis. 1981 Mar;143(3):352–363. doi: 10.1093/infdis/143.3.352. [DOI] [PubMed] [Google Scholar]
  5. Crowe J. E., Jr, Bui P. T., Siber G. R., Elkins W. R., Chanock R. M., Murphy B. R. Cold-passaged, temperature-sensitive mutants of human respiratory syncytial virus (RSV) are highly attenuated, immunogenic, and protective in seronegative chimpanzees, even when RSV antibodies are infused shortly before immunization. Vaccine. 1995 Jun;13(9):847–855. doi: 10.1016/0264-410x(94)00074-w. [DOI] [PubMed] [Google Scholar]
  6. Curran M. D., Lü Y. J., Rima B. K. The fusion protein gene of phocine distemper virus: nucleotide and deduced amino acid sequences and a comparison of morbillivirus fusion proteins. Arch Virol. 1992;126(1-4):159–169. doi: 10.1007/BF01309692. [DOI] [PubMed] [Google Scholar]
  7. Drillien R., Spehner D., Kirn A., Giraudon P., Buckland R., Wild F., Lecocq J. P. Protection of mice from fatal measles encephalitis by vaccination with vaccinia virus recombinants encoding either the hemagglutinin or the fusion protein. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1252–1256. doi: 10.1073/pnas.85.4.1252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Francis M. J., Fry C. M., Rowlands D. J., Bittle J. L., Houghten R. A., Lerner R. A., Brown F. Immune response to uncoupled peptides of foot-and-mouth disease virus. Immunology. 1987 May;61(1):1–6. [PMC free article] [PubMed] [Google Scholar]
  9. Francis M. J., Hastings G. Z., Sangar D. V., Clark R. P., Syred A., Clarke B. E., Rowlands D. J., Brown F. A synthetic peptide which elicits neutralizing antibody against human rhinovirus type 2. J Gen Virol. 1987 Oct;68(Pt 10):2687–2691. doi: 10.1099/0022-1317-68-10-2687. [DOI] [PubMed] [Google Scholar]
  10. Gnann J. W., Jr, Nelson J. A., Oldstone M. B. Fine mapping of an immunodominant domain in the transmembrane glycoprotein of human immunodeficiency virus. J Virol. 1987 Aug;61(8):2639–2641. doi: 10.1128/jvi.61.8.2639-2641.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hull J. D., Krah D. L., Choppin P. W. Resistance of a measles virus mutant to fusion inhibitory oligopeptides is not associated with mutations in the fusion peptide. Virology. 1987 Aug;159(2):368–372. doi: 10.1016/0042-6822(87)90475-2. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Muller C. P., Handtmann D., Brons N. H., Weinmann M., Wiesmüller K. H., Spahn G., Wiesneth M., Schneider F., Jung G. Analysis of antibody response to the measles virus using synthetic peptides of the fusion protein. Evidence of non-random pairing of T and B cell epitopes. Virus Res. 1993 Dec;30(3):271–280. doi: 10.1016/0168-1702(93)90095-5. [DOI] [PubMed] [Google Scholar]
  14. Norrby E., Gollmar Y. Appearance and persistence of antibodies against different virus components after regular measles infections. Infect Immun. 1972 Sep;6(3):240–247. doi: 10.1128/iai.6.3.240-247.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Obeid O. E., Partidos C. D., Howard C. R., Steward M. W. 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. J Virol. 1995 Mar;69(3):1420–1428. doi: 10.1128/jvi.69.3.1420-1428.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Obeid O. E., Partidos C. D., Steward M. W. Analysis of the antigenic profile of measles virus haemagglutinin in mice and humans using overlapping synthetic peptides. Virus Res. 1994 Apr;32(1):69–84. doi: 10.1016/0168-1702(94)90062-0. [DOI] [PubMed] [Google Scholar]
  17. Palker T. J., Matthews T. J., Langlois A., Tanner M. E., Martin M. E., Scearce R. M., Kim J. E., Berzofsky J. A., Bolognesi D. P., Haynes B. F. Polyvalent human immunodeficiency virus synthetic immunogen comprised of envelope gp120 T helper cell sites and B cell neutralization epitopes. J Immunol. 1989 May 15;142(10):3612–3619. [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Rath S., Stanley C. M., Steward M. W. An inhibition enzyme immunoassay for estimating relative antibody affinity and affinity heterogeneity. J Immunol Methods. 1988 Feb 10;106(2):245–249. doi: 10.1016/0022-1759(88)90204-9. [DOI] [PubMed] [Google Scholar]
  21. Richardson C., Hull D., Greer P., Hasel K., Berkovich A., Englund G., Bellini W., Rima B., Lazzarini R. The nucleotide sequence of the mRNA encoding the fusion protein of measles virus (Edmonston strain): a comparison of fusion proteins from several different paramyxoviruses. Virology. 1986 Dec;155(2):508–523. doi: 10.1016/0042-6822(86)90212-6. [DOI] [PubMed] [Google Scholar]
  22. Schneider-Schaulies J., Dunster L. M., Schwartz-Albiez R., Krohne G., ter Meulen V. Physical association of moesin and CD46 as a receptor complex for measles virus. J Virol. 1995 Apr;69(4):2248–2256. doi: 10.1128/jvi.69.4.2248-2256.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Steward M. W., Petty R. E. The use of ammonium sulphate globulin precipitation for determination of affinity of anti-protein antibodies in mouse serum. Immunology. 1972 May;22(5):747–756. [PMC free article] [PubMed] [Google Scholar]
  24. Steward M. W., Stanley C. M., Obeid O. E. A mimotope from a solid-phase peptide library induces a measles virus-neutralizing and protective antibody response. J Virol. 1995 Dec;69(12):7668–7673. doi: 10.1128/jvi.69.12.7668-7673.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Toyoda T., Gotoh B., Sakaguchi T., Kida H., Nagai Y. Identification of amino acids relevant to three antigenic determinants on the fusion protein of Newcastle disease virus that are involved in fusion inhibition and neutralization. J Virol. 1988 Nov;62(11):4427–4430. doi: 10.1128/jvi.62.11.4427-4430.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Whittle H., Hanlon P., O'Neill K., Hanlon L., Marsh V., Jupp E., Aaby P. Trial of high-dose Edmonston-Zagreb measles vaccine in the Gambia: antibody response and side-effects. Lancet. 1988 Oct 8;2(8615):811–814. doi: 10.1016/s0140-6736(88)92781-x. [DOI] [PubMed] [Google Scholar]
  27. Wiesmüller K. H., Spahn G., Handtmann D., Schneider F., Jung G., Muller C. P. Heterogeneity of linear B cell epitopes of the measles virus fusion protein reacting with late convalescent sera. J Gen Virol. 1992 Sep;73(Pt 9):2211–2216. doi: 10.1099/0022-1317-73-9-2211. [DOI] [PubMed] [Google Scholar]
  28. Wild T. F., Buckland R. Inhibition of measles virus infection and fusion with peptides corresponding to the leucine zipper region of the fusion protein. J Gen Virol. 1997 Jan;78(Pt 1):107–111. doi: 10.1099/0022-1317-78-1-107. [DOI] [PubMed] [Google Scholar]
  29. Wild T. F., Fayolle J., Beauverger P., Buckland R. Measles virus fusion: role of the cysteine-rich region of the fusion glycoprotein. J Virol. 1994 Nov;68(11):7546–7548. doi: 10.1128/jvi.68.11.7546-7548.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yilma T., Hsu D., Jones L., Owens S., Grubman M., Mebus C., Yamanaka M., Dale B. Protection of cattle against rinderpest with vaccinia virus recombinants expressing the HA or F gene. Science. 1988 Nov 18;242(4881):1058–1061. doi: 10.1126/science.3194758. [DOI] [PubMed] [Google Scholar]

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