Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1991 Jun;65(6):3106–3113. doi: 10.1128/jvi.65.6.3106-3113.1991

Heterotypic passive protection induced by synthetic peptides corresponding to VP7 and VP4 of bovine rotavirus.

M K Ijaz 1, S K Attah-Poku 1, M J Redmond 1, M D Parker 1, M I Sabara 1, P Frenchick 1, L A Babiuk 1
PMCID: PMC240966  PMID: 1851871

Abstract

We have evaluated the potential of two peptides derived from highly conserved regions of rotavirus outer capsid proteins (VP7 and VP4) to act as a rotavirus vaccine. The capacity of peptides coupled to rotavirus VP6 spherical particles to provide passive protection in a murine model was compared with the protection induced by peptide-keyhole limpet hemocyanin (KLH) conjugates. Female mice were immunized a total of three times before and during pregnancy. Suckling mouse pups were challenged at 7 days of age with either homologous or heterologous rotavirus serotypes. The efficacy of vaccination was determined by analyzing the clinical symptoms and measuring xylose adsorption in the intestine. In this model the VP4 peptide-VP6 conjugate provided protection equal to that obtained using bovine rotavirus (BRV) as the immunogen. The VP7 peptide-VP6 conjugate provided slightly less protection than the VP4 peptide-VP6 conjugate. A mixture of the VP4 peptide-VP6 and VP7 peptide-VP6 conjugates provided better heterologous protection than immunization with BRV. In contrast, KLH-conjugated peptides provided only partial protection. The significance of a synthetic-peptide-based rotavirus vaccine in the prevention of rotavirus infections is discussed.

Full text

PDF
3106

Images in this article

Selected References

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

  1. Aha P. M., Sabara M. I. Development of a rotavirus plaque assay using Sephadex G-75. J Virol Methods. 1990 Apr;28(1):25–31. doi: 10.1016/0166-0934(90)90084-s. [DOI] [PubMed] [Google Scholar]
  2. Arias C. F., Lizano M., López S. Synthesis in Escherichia coli and immunological characterization of a polypeptide containing the cleavage sites associated with trypsin enhancement of rotavirus SA11 infectivity. J Gen Virol. 1987 Mar;68(Pt 3):633–642. doi: 10.1099/0022-1317-68-3-633. [DOI] [PubMed] [Google Scholar]
  3. Babiuk L. A., Mohammed K., Spence L., Fauvel M., Petro R. Rotavirus isolation and cultivation in the presence of trypsin. J Clin Microbiol. 1977 Dec;6(6):610–617. doi: 10.1128/jcm.6.6.610-617.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Braun D. K., Pereira L., Norrild B., Roizman B. Application of denatured, electrophoretically separated, and immobilized lysates of herpes simplex virus-infected cells for detection of monoclonal antibodies and for studies of the properties of viral proteins. J Virol. 1983 Apr;46(1):103–112. doi: 10.1128/jvi.46.1.103-112.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bridger J. C., Oldham G. Avirulent rotavirus infections protect calves from disease with and without inducing high levels of neutralizing antibody. J Gen Virol. 1987 Sep;68(Pt 9):2311–2317. doi: 10.1099/0022-1317-68-9-2311. [DOI] [PubMed] [Google Scholar]
  6. Dharakul T., Rott L., Greenberg H. B. Recovery from chronic rotavirus infection in mice with severe combined immunodeficiency: virus clearance mediated by adoptive transfer of immune CD8+ T lymphocytes. J Virol. 1990 Sep;64(9):4375–4382. doi: 10.1128/jvi.64.9.4375-4382.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dyrberg T., Oldstone M. B. Peptides as antigens. Importance of orientation. J Exp Med. 1986 Oct 1;164(4):1344–1349. doi: 10.1084/jem.164.4.1344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eldridge J. H., Gilley R. M., Staas J. K., Moldoveanu Z., Meulbroek J. A., Tice T. R. Biodegradable microspheres: vaccine delivery system for oral immunization. Curr Top Microbiol Immunol. 1989;146:59–66. doi: 10.1007/978-3-642-74529-4_6. [DOI] [PubMed] [Google Scholar]
  9. Estes M. K., Cohen J. Rotavirus gene structure and function. Microbiol Rev. 1989 Dec;53(4):410–449. doi: 10.1128/mr.53.4.410-449.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Estes M. K., Crawford S. E., Penaranda M. E., Petrie B. L., Burns J. W., Chan W. K., Ericson B., Smith G. E., Summers M. D. Synthesis and immunogenicity of the rotavirus major capsid antigen using a baculovirus expression system. J Virol. 1987 May;61(5):1488–1494. doi: 10.1128/jvi.61.5.1488-1494.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fukuhara N., Yoshie O., Kitaoka S., Konno T. Role of VP3 in human rotavirus internalization after target cell attachment via VP7. J Virol. 1988 Jul;62(7):2209–2218. doi: 10.1128/jvi.62.7.2209-2218.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Green N., Alexander H., Olson A., Alexander S., Shinnick T. M., Sutcliffe J. G., Lerner R. A. Immunogenic structure of the influenza virus hemagglutinin. Cell. 1982 Mar;28(3):477–487. doi: 10.1016/0092-8674(82)90202-1. [DOI] [PubMed] [Google Scholar]
  13. Gunn P. R., Sato F., Powell K. F., Bellamy A. R., Napier J. R., Harding D. R., Hancock W. S., Siegman L. J., Both G. W. Rotavirus neutralizing protein VP7: antigenic determinants investigated by sequence analysis and peptide synthesis. J Virol. 1985 Jun;54(3):791–797. doi: 10.1128/jvi.54.3.791-797.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Herzenberg L. A., Tokuhisa T., Herzenberg L. A. Carrier-priming leads to hapten-specific suppression. Nature. 1980 Jun 26;285(5767):664–667. doi: 10.1038/285664a0. [DOI] [PubMed] [Google Scholar]
  15. Ho M. S., Glass R. I., Pinsky P. F., Young-Okoh N. C., Sappenfield W. M., Buehler J. W., Gunter N., Anderson L. J. Diarrheal deaths in American children. Are they preventable? JAMA. 1988 Dec 9;260(22):3281–3285. [PubMed] [Google Scholar]
  16. Ijaz M. K., Dent D., Babiuk L. A. Neuroimmunomodulation of in vivo anti-rotavirus humoral immune response. J Neuroimmunol. 1990 Feb;26(2):159–171. doi: 10.1016/0165-5728(90)90087-4. [DOI] [PubMed] [Google Scholar]
  17. Ijaz M. K., Dent D., Haines D., Babiuk L. A. Development of a murine model to study the pathogenesis of rotavirus infection. Exp Mol Pathol. 1989 Oct;51(2):186–204. doi: 10.1016/0014-4800(89)90019-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ijaz M. K., Sabara M. I., Frenchick P. J., Babiuk L. A. Assessment of intestinal damage in rotavirus infected neonatal mice by a D-xylose absorption test. J Virol Methods. 1987 Nov;18(2-3):153–157. doi: 10.1016/0166-0934(87)90120-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jackson S., Mestecky J., Childers N. K., Michalek S. M. Liposomes containing anti-idiotypic antibodies: an oral vaccine to induce protective secretory immune responses specific for pathogens of mucosal surfaces. Infect Immun. 1990 Jun;58(6):1932–1936. doi: 10.1128/iai.58.6.1932-1936.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  21. Lowell G. H., Ballou W. R., Smith L. F., Wirtz R. A., Zollinger W. D., Hockmeyer W. T. Proteosome-lipopeptide vaccines: enhancement of immunogenicity for malaria CS peptides. Science. 1988 May 6;240(4853):800–802. doi: 10.1126/science.2452484. [DOI] [PubMed] [Google Scholar]
  22. Mackow E. R., Shaw R. D., Matsui S. M., Vo P. T., Dang M. N., Greenberg H. B. The rhesus rotavirus gene encoding protein VP3: location of amino acids involved in homologous and heterologous rotavirus neutralization and identification of a putative fusion region. Proc Natl Acad Sci U S A. 1988 Feb;85(3):645–649. doi: 10.1073/pnas.85.3.645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mackow E. R., Vo P. T., Broome R., Bass D., Greenberg H. B. Immunization with baculovirus-expressed VP4 protein passively protects against simian and murine rotavirus challenge. J Virol. 1990 Apr;64(4):1698–1703. doi: 10.1128/jvi.64.4.1698-1703.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Matsuno S., Inouye S. Purification of an outer capsid glycoprotein of neonatal calf diarrhea virus and preparation of its antisera. Infect Immun. 1983 Jan;39(1):155–158. doi: 10.1128/iai.39.1.155-158.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Morein B. The iscom antigen-presenting system. Nature. 1988 Mar 17;332(6161):287–288. doi: 10.1038/332287a0. [DOI] [PubMed] [Google Scholar]
  26. O'Hagan D. T., Palin K., Davis S. S., Artursson P., Sjöholm I. Microparticles as potentially orally active immunological adjuvants. Vaccine. 1989 Oct;7(5):421–424. doi: 10.1016/0264-410x(89)90156-4. [DOI] [PubMed] [Google Scholar]
  27. Offit P. A., Dudzik K. I. Rotavirus-specific cytotoxic T lymphocytes passively protect against gastroenteritis in suckling mice. J Virol. 1990 Dec;64(12):6325–6328. doi: 10.1128/jvi.64.12.6325-6328.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Petrov R. V., Khaitov R. M., Zhdanov V. M., Sinyakov M. S., Norimov A. Sh, Nekrasov A. V., Podchernyaeva RYa, Kharitonenkov I. G., Shchipanova M. V. Influenza virus antigens conjugated with a synthetic polyelectrolyte: a novel model of vaccines. Vaccine. 1985 Dec;3(5):392–400. doi: 10.1016/0264-410x(85)90130-6. [DOI] [PubMed] [Google Scholar]
  29. Potter A. A., Cox G., Parker M., Babiuk L. A. The complete nucleotide sequence of bovine rotavirus C486 gene 4 cDNA. Nucleic Acids Res. 1987 May 26;15(10):4361–4361. doi: 10.1093/nar/15.10.4361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Prasad B. V., Burns J. W., Marietta E., Estes M. K., Chiu W. Localization of VP4 neutralization sites in rotavirus by three-dimensional cryo-electron microscopy. Nature. 1990 Feb 1;343(6257):476–479. doi: 10.1038/343476a0. [DOI] [PubMed] [Google Scholar]
  31. Ready K. F., Sabara M. In vitro assembly of bovine rotavirus nucleocapsid protein. Virology. 1987 Mar;157(1):189–198. doi: 10.1016/0042-6822(87)90328-x. [DOI] [PubMed] [Google Scholar]
  32. Sabara M., Gilchrist J. E., Hudson G. R., Babiuk L. A. Preliminary characterization of an epitope involved in neutralization and cell attachment that is located on the major bovine rotavirus glycoprotein. J Virol. 1985 Jan;53(1):58–66. doi: 10.1128/jvi.53.1.58-66.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sabara M., Ready K. F., Frenchick P. J., Babiuk L. A. Biochemical evidence for the oligomeric arrangement of bovine rotavirus nucleocapsid protein and its possible significance in the immunogenicity of this protein. J Gen Virol. 1987 Jan;68(Pt 1):123–133. doi: 10.1099/0022-1317-68-1-123. [DOI] [PubMed] [Google Scholar]
  34. Schaaper W. M., Lankhof H., Puijk W. C., Meloen R. H. Manipulation of antipeptide immune response by varying the coupling of the peptide with the carrier protein. Mol Immunol. 1989 Jan;26(1):81–85. doi: 10.1016/0161-5890(89)90023-0. [DOI] [PubMed] [Google Scholar]
  35. Schutze M. P., Leclerc C., Jolivet M., Audibert F., Chedid L. Carrier-induced epitopic suppression, a major issue for future synthetic vaccines. J Immunol. 1985 Oct;135(4):2319–2322. [PubMed] [Google Scholar]
  36. Shaw R. D., Fong K. J., Losonsky G. A., Levine M. M., Maldonado Y., Yolken R., Flores J., Kapikian A. Z., Vo P. T., Greenberg H. B. Epitope-specific immune responses to rotavirus vaccination. Gastroenterology. 1987 Nov;93(5):941–950. doi: 10.1016/0016-5085(87)90555-5. [DOI] [PubMed] [Google Scholar]
  37. Taniguchi K., Maloy W. L., Nishikawa K., Green K. Y., Hoshino Y., Urasawa S., Kapikian A. Z., Chanock R. M., Gorziglia M. Identification of cross-reactive and serotype 2-specific neutralization epitopes on VP3 of human rotavirus. J Virol. 1988 Jul;62(7):2421–2426. doi: 10.1128/jvi.62.7.2421-2426.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ward R. L., Knowlton D. R., Schiff G. M., Hoshino Y., Greenberg H. B. Relative concentrations of serum neutralizing antibody to VP3 and VP7 proteins in adults infected with a human rotavirus. J Virol. 1988 May;62(5):1543–1549. doi: 10.1128/jvi.62.5.1543-1549.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Woode G. N., Zheng S. L., Rosen B. I., Knight N., Gourley N. E., Ramig R. F. Protection between different serotypes of bovine rotavirus in gnotobiotic calves: specificity of serum antibody and coproantibody responses. J Clin Microbiol. 1987 Jun;25(6):1052–1058. doi: 10.1128/jcm.25.6.1052-1058.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES