Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1990 Dec;64(12):6090–6100. doi: 10.1128/jvi.64.12.6090-6100.1990

Structural factors modulate the activity of antigenic poliovirus sequences expressed on hybrid hepatitis B surface antigen particles.

F Delpeyroux 1, E Van Wezel 1, B Blondel 1, R Crainic 1
PMCID: PMC248783  PMID: 2173781

Abstract

We have studied the functional expression of antigenic poliovirus fragments carried by various hybrid hepatitis B surface antigen (HBsAg) particles. Several constructions were made by using two different insertion sites in the HBsAg molecule (amino acid positions 50 and 113) and two different sequences, one derived from poliovirus type 1 (PV-1) and the other from PV-2. The inserted fragments each encompassed residues 93 to 103 of the capsid protein VP1, a segment which includes the linear part of the neutralization antigenic site 1 of the poliovirus. The antigenicity and immunogenicity of the hybrid particles were evaluated and compared in terms of poliovirus neutralization. A high level of antigenic and immunogenic activity of the PV-1 fragment was obtained by insertion at position 113 but not at position 50 of HBsAg. However, a cooperative effect was observed when two PV-1 fragments were inserted at both positions of the same HBsAg molecule. Antibodies elicited by the PV-2 fragment inserted at amino acid position 113 did not bind or neutralize the corresponding poliovirus strain. They did, however, bind a chimeric poliovirus in which the homologous antigenic fragment of PV-1 had been replaced by that of PV-2. The only virions that were neutralized by these antibodies were certain mutants carrying amino acid substitutions within the PV-2 fragment. These results show that position, constraints from the carrier protein, and nature of the inserted sequences are critically important in favoring or limiting the expression of antigenic fragments as viral neutralization immunogens.

Full text

PDF
6090

Images in this article

6092Image
on p.6092
6093Image
on p.6093
6093Image
on p.6093
6096Image
on p.6096

Selected References

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

  1. Acharya R., Fry E., Stuart D., Fox G., Rowlands D., Brown F. The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution. Nature. 1989 Feb 23;337(6209):709–716. doi: 10.1038/337709a0. [DOI] [PubMed] [Google Scholar]
  2. Adams S. E., Dawson K. M., Gull K., Kingsman S. M., Kingsman A. J. The expression of hybrid HIV:Ty virus-like particles in yeast. Nature. 1987 Sep 3;329(6134):68–70. doi: 10.1038/329068a0. [DOI] [PubMed] [Google Scholar]
  3. Berzofsky J. A. Intrinsic and extrinsic factors in protein antigenic structure. Science. 1985 Sep 6;229(4717):932–940. doi: 10.1126/science.2410982. [DOI] [PubMed] [Google Scholar]
  4. Blondel B., Crainic R., Fichot O., Dufraisse G., Candrea A., Diamond D., Girard M., Horaud F. Mutations conferring resistance to neutralization with monoclonal antibodies in type 1 poliovirus can be located outside or inside the antibody-binding site. J Virol. 1986 Jan;57(1):81–90. doi: 10.1128/jvi.57.1.81-90.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown S. E., Howard C. R., Zuckerman A. J., Steward M. W. Affinity of antibody responses in man to hepatitis B vaccine determined with synthetic peptides. Lancet. 1984 Jul 28;2(8396):184–187. doi: 10.1016/s0140-6736(84)90479-3. [DOI] [PubMed] [Google Scholar]
  6. Charbit A., Van der Werf S., Mimic V., Boulain J. C., Girard M., Hofnung M. Expression of a poliovirus neutralization epitope at the surface of recombinant bacteria: first immunization results. Ann Inst Pasteur Microbiol. 1988 Jan-Feb;139(1):45–58. doi: 10.1016/0769-2609(88)90096-8. [DOI] [PubMed] [Google Scholar]
  7. Chow M., Yabrov R., Bittle J., Hogle J., Baltimore D. Synthetic peptides from four separate regions of the poliovirus type 1 capsid protein VP1 induce neutralizing antibodies. Proc Natl Acad Sci U S A. 1985 Feb;82(3):910–914. doi: 10.1073/pnas.82.3.910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clarke B. E., Newton S. E., Carroll A. R., Francis M. J., Appleyard G., Syred A. D., Highfield P. E., Rowlands D. J., Brown F. Improved immunogenicity of a peptide epitope after fusion to hepatitis B core protein. 1987 Nov 26-Dec 2Nature. 330(6146):381–384. doi: 10.1038/330381a0. [DOI] [PubMed] [Google Scholar]
  9. Colbère-Garapin F., Christodoulou C., Crainic R., Garapin A. C., Candrea A. Addition of a foreign oligopeptide to the major capsid protein of poliovirus. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8668–8672. doi: 10.1073/pnas.85.22.8668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Colbère-Garapin F., Horodniceanu F., Kourilsky P., Garapin A. C. A new dominant hybrid selective marker for higher eukaryotic cells. J Mol Biol. 1981 Jul 25;150(1):1–14. doi: 10.1016/0022-2836(81)90321-1. [DOI] [PubMed] [Google Scholar]
  11. Crainic R., Couillin P., Blondel B., Cabau N., Boué A., Horodniceanu F. Natural variation of poliovirus neutralization epitopes. Infect Immun. 1983 Sep;41(3):1217–1225. doi: 10.1128/iai.41.3.1217-1225.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Delpeyroux F., Chenciner N., Lim A., Lambert M., Malpièce Y., Streeck R. E. Insertions in the hepatitis B surface antigen. Effect on assembly and secretion of 22-nm particles from mammalian cells. J Mol Biol. 1987 May 20;195(2):343–350. doi: 10.1016/0022-2836(87)90655-3. [DOI] [PubMed] [Google Scholar]
  13. Delpeyroux F., Chenciner N., Lim A., Malpièce Y., Blondel B., Crainic R., van der Werf S., Streeck R. E. A poliovirus neutralization epitope expressed on hybrid hepatitis B surface antigen particles. Science. 1986 Jul 25;233(4762):472–475. doi: 10.1126/science.2425433. [DOI] [PubMed] [Google Scholar]
  14. Delpeyroux F., Crainic R., Blondel B., Horaud F., Van der Werf S., Girard M., Lagarde D., Mazert M. C., Streeck R. E. Construction and characterization of hybrid hepatitis B antigen particles carrying a poliovirus immunogen. Biochimie. 1988 Aug;70(8):1065–1073. doi: 10.1016/0300-9084(88)90269-6. [DOI] [PubMed] [Google Scholar]
  15. Delpeyroux F., Peillon N., Blondel B., Crainic R., Streeck R. E. Presentation and immunogenicity of the hepatitis B surface antigen and a poliovirus neutralization antigen on mixed empty envelope particles. J Virol. 1988 May;62(5):1836–1839. doi: 10.1128/jvi.62.5.1836-1839.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Emini E. A., Jameson B. A., Wimmer E. Priming for and induction of anti-poliovirus neutralizing antibodies by synthetic peptides. Nature. 1983 Aug 25;304(5928):699–703. doi: 10.1038/304699a0. [DOI] [PubMed] [Google Scholar]
  18. Evans D. J., McKeating J., Meredith J. M., Burke K. L., Katrak K., John A., Ferguson M., Minor P. D., Weiss R. A., Almond J. W. An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies. Nature. 1989 Jun 1;339(6223):385-8, 340. doi: 10.1038/339385a0. [DOI] [PubMed] [Google Scholar]
  19. Ferguson M., Evans D. M., Magrath D. I., Minor P. D., Almond J. W., Schild G. C. Induction by synthetic peptides of broadly reactive, type-specific neutralizing antibody to poliovirus type 3. Virology. 1985 Jun;143(2):505–515. doi: 10.1016/0042-6822(85)90389-7. [DOI] [PubMed] [Google Scholar]
  20. Geysen H. M., Barteling S. J., Meloen R. H. Small peptides induce antibodies with a sequence and structural requirement for binding antigen comparable to antibodies raised against the native protein. Proc Natl Acad Sci U S A. 1985 Jan;82(1):178–182. doi: 10.1073/pnas.82.1.178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Geysen H. M., Tainer J. A., Rodda S. J., Mason T. J., Alexander H., Getzoff E. D., Lerner R. A. Chemistry of antibody binding to a protein. Science. 1987 Mar 6;235(4793):1184–1190. doi: 10.1126/science.3823878. [DOI] [PubMed] [Google Scholar]
  22. Hogle J. M., Chow M., Filman D. J. Three-dimensional structure of poliovirus at 2.9 A resolution. Science. 1985 Sep 27;229(4720):1358–1365. doi: 10.1126/science.2994218. [DOI] [PubMed] [Google Scholar]
  23. Horaud F., Crainic R., Van der Werf S., Blondel B., Wichowski C., Akacem O., Bruneau P., Couillin P., Siffert O., Girard M. Identification and characterization of a continuous neutralization epitope (C3) present on type 1 poliovirus. Prog Med Virol. 1987;34:129–155. [PubMed] [Google Scholar]
  24. Kingsman S. M., Kingsman A. J. Polyvalent recombinant antigens: a new vaccine strategy. Vaccine. 1988 Aug;6(4):304–306. doi: 10.1016/0264-410x(88)90174-0. [DOI] [PubMed] [Google Scholar]
  25. La Monica N., Kupsky W. J., Racaniello V. R. Reduced mouse neurovirulence of poliovirus type 2 Lansing antigenic variants selected with monoclonal antibodies. Virology. 1987 Dec;161(2):429–437. doi: 10.1016/0042-6822(87)90136-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. LeClerc C., Martineau P., Van der Werf S., Deriaud E., Duplay P., Hofnung M. Induction of virus-neutralizing antibodies by bacteria expressing the C3 poliovirus epitope in the periplasm. The route of immunization influences the isotypic distribution and the biologic activity of the antipoliovirus antibodies. J Immunol. 1990 Apr 15;144(8):3174–3182. [PubMed] [Google Scholar]
  27. Martin A., Wychowski C., Couderc T., Crainic R., Hogle J., Girard M. Engineering a poliovirus type 2 antigenic site on a type 1 capsid results in a chimaeric virus which is neurovirulent for mice. EMBO J. 1988 Sep;7(9):2839–2847. doi: 10.1002/j.1460-2075.1988.tb03140.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Meloen R. H., Puyk W. C., Meijer D. J., Lankhof H., Posthumus W. P., Schaaper W. M. Antigenicity and immunogenicity of synthetic peptides of foot-and-mouth disease virus. J Gen Virol. 1987 Feb;68(Pt 2):305–314. doi: 10.1099/0022-1317-68-2-305. [DOI] [PubMed] [Google Scholar]
  29. Michel M. L., Mancini M., Sobczak E., Favier V., Guetard D., Bahraoui E. M., Tiollais P. Induction of anti-human immunodeficiency virus (HIV) neutralizing antibodies in rabbits immunized with recombinant HIV--hepatitis B surface antigen particles. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7957–7961. doi: 10.1073/pnas.85.21.7957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Minor P. D., Ferguson M., Evans D. M., Almond J. W., Icenogle J. P. Antigenic structure of polioviruses of serotypes 1, 2 and 3. J Gen Virol. 1986 Jul;67(Pt 7):1283–1291. doi: 10.1099/0022-1317-67-7-1283. [DOI] [PubMed] [Google Scholar]
  31. Mishiro S., Imai M., Takahashi K., Machida A., Gotanda T., Miyakawa Y., Mayumi M. A 49,000-dalton polypeptide bearing all antigenic determinants and full immunogenicity of 22-nm hepatitis B surface antigen particles. J Immunol. 1980 Apr;124(4):1589–1593. [PubMed] [Google Scholar]
  32. Murdin A. D., Wimmer E. Construction of a poliovirus type 1/type 2 antigenic hybrid by manipulation of neutralization antigenic site II. J Virol. 1989 Dec;63(12):5251–5257. doi: 10.1128/jvi.63.12.5251-5257.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Murray M. G., Bradley J., Yang X. F., Wimmer E., Moss E. G., Racaniello V. R. Poliovirus host range is determined by a short amino acid sequence in neutralization antigenic site I. Science. 1988 Jul 8;241(4862):213–215. doi: 10.1126/science.2838906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Page G. S., Mosser A. G., Hogle J. M., Filman D. J., Rueckert R. R., Chow M. Three-dimensional structure of poliovirus serotype 1 neutralizing determinants. J Virol. 1988 May;62(5):1781–1794. doi: 10.1128/jvi.62.5.1781-1794.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Peterson D. L. The structure of hepatitis B surface antigen and its antigenic sites. Bioessays. 1987 Jun;6(6):258–262. doi: 10.1002/bies.950060604. [DOI] [PubMed] [Google Scholar]
  36. Phalipon A., Crainic R., Kaczorek M. Expression of a poliovirus type 1 neutralization epitope on a diphtheria toxin fusion protein. Vaccine. 1989 Apr;7(2):132–136. doi: 10.1016/0264-410x(89)90052-2. [DOI] [PubMed] [Google Scholar]
  37. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Smith G. P. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science. 1985 Jun 14;228(4705):1315–1317. doi: 10.1126/science.4001944. [DOI] [PubMed] [Google Scholar]
  40. Stahl S. J., Murray K. Immunogenicity of peptide fusions to hepatitis B virus core antigen. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6283–6287. doi: 10.1073/pnas.86.16.6283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tiollais P., Pourcel C., Dejean A. The hepatitis B virus. Nature. 1985 Oct 10;317(6037):489–495. doi: 10.1038/317489a0. [DOI] [PubMed] [Google Scholar]
  42. Uytdehaag F. G., Osterhaus A. D. Induction of neutralizing antibody in mice against poliovirus type II with monoclonal anti-idiotypic antibody. J Immunol. 1985 Feb;134(2):1225–1229. [PubMed] [Google Scholar]
  43. Walter G. Production and use of antibodies against synthetic peptides. J Immunol Methods. 1986 Apr 17;88(2):149–161. doi: 10.1016/0022-1759(86)90001-3. [DOI] [PubMed] [Google Scholar]
  44. Wiegers K., Uhlig H., Dernick R. N-AgIB of poliovirus type 1: a discontinuous epitope formed by two loops of VP1 comprising residues 96-104 and 141-152. Virology. 1989 Jun;170(2):583–586. doi: 10.1016/0042-6822(89)90452-2. [DOI] [PubMed] [Google Scholar]
  45. Young R. A., Davis R. W. Efficient isolation of genes by using antibody probes. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1194–1198. doi: 10.1073/pnas.80.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. van der Werf S., Wychowski C., Bruneau P., Blondel B., Crainic R., Horodniceanu F., Girard M. Localization of a poliovirus type 1 neutralization epitope in viral capsid polypeptide VP1. Proc Natl Acad Sci U S A. 1983 Aug;80(16):5080–5084. doi: 10.1073/pnas.80.16.5080. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES