Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1988 Aug;62(8):3032–3036. doi: 10.1128/jvi.62.8.3032-3036.1988

Vaccination against lethal coronavirus-induced encephalitis with a synthetic decapeptide homologous to a domain in the predicted peplomer stalk.

P J Talbot 1, G Dionne 1, M Lacroix 1
PMCID: PMC253743  PMID: 2455823

Abstract

A surface probability method was used to select a decapeptide homologous to residues 993 to 1002 of the peplomer protein E2 of murine hepatitis virus strain JHM, a neurotropic coronavirus. This sequence of amino acids corresponded to a minor peak on a hydrophilicity plot. Immunization of mice with the chemically synthesized peptide coupled to keyhole limpet hemocyanin elicited high levels of neutralizing antibody and protected against lethal virus challenge. Protection correlated with a critical level of antipeptide antibody, which could be reached after a single inoculation. These results suggest that an appropriate antibody response to a highly restricted, surface-exposed domain of this viral protein is critical in determining the outcome of infection of the central nervous system. This sequence is located in the C-terminal fifth of the E2 peplomers, between two predicted coiled-coil structures.

Full text

PDF
3032

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnon R., Sela M. Synthetic vaccines: present and future. Ann Inst Pasteur Immunol. 1985 Nov-Dec;136D(3):271–282. doi: 10.1016/s0769-2625(85)80112-4. [DOI] [PubMed] [Google Scholar]
  2. Bittle J. L., Houghten R. A., Alexander H., Shinnick T. M., Sutcliffe J. G., Lerner R. A., Rowlands D. J., Brown F. Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence. Nature. 1982 Jul 1;298(5869):30–33. doi: 10.1038/298030a0. [DOI] [PubMed] [Google Scholar]
  3. Buchmeier M. J., Lewicki H. A., Talbot P. J., Knobler R. L. Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody. Virology. 1984 Jan 30;132(2):261–270. doi: 10.1016/0042-6822(84)90033-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burks J. S., DeVald B. L., Jankovsky L. D., Gerdes J. C. Two coronaviruses isolated from central nervous system tissue of two multiple sclerosis patients. Science. 1980 Aug 22;209(4459):933–934. doi: 10.1126/science.7403860. [DOI] [PubMed] [Google Scholar]
  5. Bächi T., Gerhard W., Yewdell J. W. Monoclonal antibodies detect different forms of influenza virus hemagglutinin during viral penetration and biosynthesis. J Virol. 1985 Aug;55(2):307–313. doi: 10.1128/jvi.55.2.307-313.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chanh T. C., Kennedy R. C., Alderete B. E., Kanda P., Eichberg J. W., Dreesman G. R. Human immunodeficiency virus gp120 glycoprotein detected by a monoclonal antibody to a synthetic peptide. Eur J Immunol. 1986 Nov;16(11):1465–1468. doi: 10.1002/eji.1830161126. [DOI] [PubMed] [Google Scholar]
  7. Chiodi F., von Gegerfeldt A., Albert J., Fenyö E. M., Gaines H., von Sydow M., Biberfeld G., Parks E., Norrby E. Site-directed ELISA with synthetic peptides representing the HIV transmembrane glycoprotein. J Med Virol. 1987 Sep;23(1):1–9. doi: 10.1002/jmv.1890230102. [DOI] [PubMed] [Google Scholar]
  8. Chou P. Y., Fasman G. D. Prediction of protein conformation. Biochemistry. 1974 Jan 15;13(2):222–245. doi: 10.1021/bi00699a002. [DOI] [PubMed] [Google Scholar]
  9. Collins A. R., Knobler R. L., Powell H., Buchmeier M. J. Monoclonal antibodies to murine hepatitis virus-4 (strain JHM) define the viral glycoprotein responsible for attachment and cell--cell fusion. Virology. 1982 Jun;119(2):358–371. doi: 10.1016/0042-6822(82)90095-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dalziel R. G., Lampert P. W., Talbot P. J., Buchmeier M. J. Site-specific alteration of murine hepatitis virus type 4 peplomer glycoprotein E2 results in reduced neurovirulence. J Virol. 1986 Aug;59(2):463–471. doi: 10.1128/jvi.59.2.463-471.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Daniel C., Talbot P. J. Physico-chemical properties of murine hepatitis virus, strain A 59. Brief report. Arch Virol. 1987;96(3-4):241–248. doi: 10.1007/BF01320963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DeLisi C., Berzofsky J. A. T-cell antigenic sites tend to be amphipathic structures. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7048–7052. doi: 10.1073/pnas.82.20.7048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. DiMarchi R., Brooke G., Gale C., Cracknell V., Doel T., Mowat N. Protection of cattle against foot-and-mouth disease by a synthetic peptide. Science. 1986 May 2;232(4750):639–641. doi: 10.1126/science.3008333. [DOI] [PubMed] [Google Scholar]
  14. Dreesman G. R., Sanchez Y., Ionescu-Matiu I., Sparrow J. T., Six H. R., Peterson D. L., Hollinger F. B., Melnick J. L. Antibody to hepatitis B surface antigen after a single inoculation of uncoupled synthetic HBsAg peptides. Nature. 1982 Jan 14;295(5845):158–160. doi: 10.1038/295158a0. [DOI] [PubMed] [Google Scholar]
  15. Eisenberg R. J., Cerini C. P., Heilman C. J., Joseph A. D., Dietzschold B., Golub E., Long D., Ponce de Leon M., Cohen G. H. Synthetic glycoprotein D-related peptides protect mice against herpes simplex virus challenge. J Virol. 1985 Dec;56(3):1014–1017. doi: 10.1128/jvi.56.3.1014-1017.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Emini E. A., Hughes J. V., Perlow D. S., Boger J. Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide. J Virol. 1985 Sep;55(3):836–839. doi: 10.1128/jvi.55.3.836-839.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fleming J. O., Trousdale M. D., el-Zaatari F. A., Stohlman S. A., Weiner L. P. Pathogenicity of antigenic variants of murine coronavirus JHM selected with monoclonal antibodies. J Virol. 1986 Jun;58(3):869–875. doi: 10.1128/jvi.58.3.869-875.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gerin J. L., Alexander H., Shih J. W., Purcell R. H., Dapolito G., Engle R., Green N., Sutcliffe J. G., Shinnick T. M., Lerner R. A. Chemically synthesized peptides of hepatitis B surface antigen duplicate the d/y specificities and induce subtype-specific antibodies in chimpanzees. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2365–2369. doi: 10.1073/pnas.80.8.2365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gilmore W., Fleming J. O., Stohlman S. A., Weiner L. P. Characterization of the structural proteins of the murine coronavirus strain A59 using monoclonal antibodies. Proc Soc Exp Biol Med. 1987 Jun;185(2):177–186. doi: 10.3181/00379727-185-42532. [DOI] [PubMed] [Google Scholar]
  20. Gnann J. W., Jr, Schwimmbeck P. L., Nelson J. A., Truax A. B., Oldstone M. B. Diagnosis of AIDS by using a 12-amino acid peptide representing an immunodominant epitope of the human immunodeficiency virus. J Infect Dis. 1987 Aug;156(2):261–267. doi: 10.1093/infdis/156.2.261. [DOI] [PubMed] [Google Scholar]
  21. Gollins S. W., Porterfield J. S. A new mechanism for the neutralization of enveloped viruses by antiviral antibody. Nature. 1986 May 15;321(6067):244–246. doi: 10.1038/321244a0. [DOI] [PubMed] [Google Scholar]
  22. Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Janin J., Wodak S. Conformation of amino acid side-chains in proteins. J Mol Biol. 1978 Nov 5;125(3):357–386. doi: 10.1016/0022-2836(78)90408-4. [DOI] [PubMed] [Google Scholar]
  24. Kaiser E., Colescott R. L., Bossinger C. D., Cook P. I. Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal Biochem. 1970 Apr;34(2):595–598. doi: 10.1016/0003-2697(70)90146-6. [DOI] [PubMed] [Google Scholar]
  25. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  26. Liu F. T., Zinnecker M., Hamaoka T., Katz D. H. New procedures for preparation and isolation of conjugates of proteins and a synthetic copolymer of D-amino acids and immunochemical characterization of such conjugates. Biochemistry. 1979 Feb 20;18(4):690–693. doi: 10.1021/bi00571a022. [DOI] [PubMed] [Google Scholar]
  27. Luytjes W., Sturman L. S., Bredenbeek P. J., Charite J., van der Zeijst B. A., Horzinek M. C., Spaan W. J. Primary structure of the glycoprotein E2 of coronavirus MHV-A59 and identification of the trypsin cleavage site. Virology. 1987 Dec;161(2):479–487. doi: 10.1016/0042-6822(87)90142-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Macnaughton M. R. Occurrence and frequency of coronavirus infections in humans as determined by enzyme-linked immunosorbent assay. Infect Immun. 1982 Nov;38(2):419–423. doi: 10.1128/iai.38.2.419-423.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Makino S., Fleming J. O., Keck J. G., Stohlman S. A., Lai M. M. RNA recombination of coronaviruses: localization of neutralizing epitopes and neuropathogenic determinants on the carboxyl terminus of peplomers. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6567–6571. doi: 10.1073/pnas.84.18.6567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Milich D. R., McLachlan A., Chisari F. V., Thornton G. B. Nonoverlapping T and B cell determinants on an hepatitis B surface antigen pre-S(2) region synthetic peptide. J Exp Med. 1986 Aug 1;164(2):532–547. doi: 10.1084/jem.164.2.532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mitchison N. A. The carrier effect in the secondary response to hapten-protein conjugates. I. Measurement of the effect with transferred cells and objections to the local environment hypothesis. Eur J Immunol. 1971 Jan;1(1):10–17. doi: 10.1002/eji.1830010103. [DOI] [PubMed] [Google Scholar]
  32. Müller G. M., Shapira M., Arnon R. Anti-influenza response achieved by immunization with a synthetic conjugate. Proc Natl Acad Sci U S A. 1982 Jan;79(2):569–573. doi: 10.1073/pnas.79.2.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Salmi A., Ziola B., Hovi T., Reunanen M. Antibodies to coronaviruses OC43 and 229E in multiple sclerosis patients. Neurology. 1982 Mar;32(3):292–295. doi: 10.1212/wnl.32.3.292. [DOI] [PubMed] [Google Scholar]
  34. Schmidt I., Skinner M., Siddell S. Nucleotide sequence of the gene encoding the surface projection glycoprotein of coronavirus MHV-JHM. J Gen Virol. 1987 Jan;68(Pt 1):47–56. doi: 10.1099/0022-1317-68-1-47. [DOI] [PubMed] [Google Scholar]
  35. Shapira M., Jibson M., Muller G., Arnon R. Immunity and protection against influenza virus by synthetic peptide corresponding to antigenic sites of hemagglutinin. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2461–2465. doi: 10.1073/pnas.81.8.2461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Shinnick T. M., Sutcliffe J. G., Green N., Lerner R. A. Synthetic peptide immunogens as vaccines. Annu Rev Microbiol. 1983;37:425–446. doi: 10.1146/annurev.mi.37.100183.002233. [DOI] [PubMed] [Google Scholar]
  37. Siddell S., Wege H., Ter Meulen V. The biology of coronaviruses. J Gen Virol. 1983 Apr;64(Pt 4):761–776. doi: 10.1099/0022-1317-64-4-761. [DOI] [PubMed] [Google Scholar]
  38. Sturman L. S., Ricard C. S., Holmes K. V. Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: activation of cell-fusing activity of virions by trypsin and separation of two different 90K cleavage fragments. J Virol. 1985 Dec;56(3):904–911. doi: 10.1128/jvi.56.3.904-911.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Talbot P. J., Buchmeier M. J. Antigenic variation among murine coronaviruses: evidence for polymorphism on the peplomer glycoprotein, E2. Virus Res. 1985 Jun;2(4):317–328. doi: 10.1016/0168-1702(85)90028-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Talbot P. J., Salmi A. A., Knobler R. L., Buchmeier M. J. Topographical mapping of epitopes on the glycoproteins of murine hepatitis virus-4 (strain JHM): correlation with biological activities. Virology. 1984 Jan 30;132(2):250–260. doi: 10.1016/0042-6822(84)90032-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tanaka R., Iwasaki Y., Koprowski H. Intracisternal virus-like particles in brain of a multiple sclerosis patient. J Neurol Sci. 1976 May;28(1):121–126. doi: 10.1016/0022-510X(76)90053-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Watari E., Dietzschold B., Szokan G., Heber-Katz E. A synthetic peptide induces long-term protection from lethal infection with herpes simplex virus 2. J Exp Med. 1987 Feb 1;165(2):459–470. doi: 10.1084/jem.165.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wege H., Dörries R., Wege H. Hybridoma antibodies to the murine coronavirus JHM: characterization of epitopes on the peplomer protein (E2). J Gen Virol. 1984 Nov;65(Pt 11):1931–1942. doi: 10.1099/0022-1317-65-11-1931. [DOI] [PubMed] [Google Scholar]
  44. Wege H., Siddell S., ter Meulen V. The biology and pathogenesis of coronaviruses. Curr Top Microbiol Immunol. 1982;99:165–200. doi: 10.1007/978-3-642-68528-6_5. [DOI] [PubMed] [Google Scholar]
  45. Wiley D. C., Wilson I. A., Skehel J. J. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature. 1981 Jan 29;289(5796):373–378. doi: 10.1038/289373a0. [DOI] [PubMed] [Google Scholar]
  46. de Groot R. J., Luytjes W., Horzinek M. C., van der Zeijst B. A., Spaan W. J., Lenstra J. A. Evidence for a coiled-coil structure in the spike proteins of coronaviruses. J Mol Biol. 1987 Aug 20;196(4):963–966. doi: 10.1016/0022-2836(87)90422-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES