Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1997 Sep;71(9):6905–6912. doi: 10.1128/jvi.71.9.6905-6912.1997

Poliovirus Sabin type 1 neutralization epitopes recognized by immunoglobulin A monoclonal antibodies.

L Fiore 1, B Ridolfi 1, D Genovese 1, G Buttinelli 1, S Lucioli 1, A Lahm 1, F M Ruggeri 1
PMCID: PMC191973  PMID: 9261417

Abstract

Immunity to poliomyelitis is largely dependent on humoral neutralizing antibodies, both after natural (wild virus or vaccine) infection and after inactivated poliovirus vaccine inoculation. Although the production of local secretory immunoglobulin A (IgA) antibody in the gut mucosa may play a major role in protection, most of information about the antigenic determinants involved in neutralization of polioviruses derives from studies conducted with humoral monoclonal antibodies (MAbs) generated from parenterally immunized mice. To investigate the specificity of the mucosal immune response to the virus, we have produced a library of IgA MAbs directed at Sabin type 1 poliovirus by oral immunization of mice with live virus in combination with cholera toxin. The epitopes recognized by 13 neutralizing MAbs were characterized by generating neutralization-escape virus mutants. Cross-neutralization analysis of viral mutants with MAbs allowed these epitopes to be divided into four groups of reactivity. To determine the epitope specificity of MAbs, virus variants were sequenced and the mutations responsible for resistance to the antibodies were located. Eight neutralizing MAbs were found to be directed at neutralization site N-AgIII in capsid protein VP3; four more MAbs recognized site N-AgII in VP1 or VP2. One IgA MAb selected a virus variant which presented a unique mutation at amino acid 138 in VP2, not previously described. This site appears to be partially related with site N-AgII and is located in a loop region facing the VP2 N-Ag-II loop around residue 164. Only 2 of 13 MAbs proved able to neutralize the wild-type Mahoney strain of poliovirus. The IgA antibodies studied were found to be produced in the dimeric form needed for recognition by the polyimmunoglobulin receptor mediating secretory antibody transport at the mucosal level.

Full Text

The Full Text of this article is available as a PDF (863.6 KB).

Selected References

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

  1. BODIAN D. Emerging concept of poliomyelitis infection. Science. 1955 Jul 15;122(3159):105–108. doi: 10.1126/science.122.3159.105. [DOI] [PubMed] [Google Scholar]
  2. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  3. Blondel B., Akacem O., Crainic R., Couillin P., Horodniceanu F. Detection by monoclonal antibodies of an antigenic determinant critical for poliovirus neutralization present on VP1 and on heat-inactivated virions. Virology. 1983 Apr 30;126(2):707–710. doi: 10.1016/s0042-6822(83)80027-0. [DOI] [PubMed] [Google Scholar]
  4. Burns J. W., Siadat-Pajouh M., Krishnaney A. A., Greenberg H. B. Protective effect of rotavirus VP6-specific IgA monoclonal antibodies that lack neutralizing activity. Science. 1996 Apr 5;272(5258):104–107. doi: 10.1126/science.272.5258.104. [DOI] [PubMed] [Google Scholar]
  5. Carlsson B., Zaman S., Mellander L., Jalil F., Hanson L. A. Secretory and serum immunoglobulin class-specific antibodies to poliovirus after vaccination. J Infect Dis. 1985 Dec;152(6):1238–1244. doi: 10.1093/infdis/152.6.1238. [DOI] [PubMed] [Google Scholar]
  6. Chen K. S., Strober W. Cholera holotoxin and its B subunit enhance Peyer's patch B cell responses induced by orally administered influenza virus: disproportionate cholera toxin enhancement of the IgA B cell response. Eur J Immunol. 1990 Feb;20(2):433–436. doi: 10.1002/eji.1830200230. [DOI] [PubMed] [Google Scholar]
  7. Conti C., Genovese D., Santoro R., Stein M. L., Orsi N., Fiore L. Activities and mechanisms of action of halogen-substituted flavanoids against poliovirus type 2 infection in vitro. Antimicrob Agents Chemother. 1990 Mar;34(3):460–466. doi: 10.1128/aac.34.3.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Diamond D. C., Jameson B. A., Bonin J., Kohara M., Abe S., Itoh H., Komatsu T., Arita M., Kuge S., Nomoto A. Antigenic variation and resistance to neutralization in poliovirus type 1. Science. 1985 Sep 13;229(4718):1090–1093. doi: 10.1126/science.2412292. [DOI] [PubMed] [Google Scholar]
  9. Equestre M., Genovese D., Cavalieri F., Fiore L., Santoro R., Perez Bercoff R. Identification of a consistent pattern of mutations in neurovirulent variants derived from the sabin vaccine strain of poliovirus type 2. J Virol. 1991 May;65(5):2707–2710. doi: 10.1128/jvi.65.5.2707-2710.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Evans D. M., Minor P. D., Schild G. S., Almond J. W. Critical role of an eight-amino acid sequence of VP1 in neutralization of poliovirus type 3. Nature. 1983 Aug 4;304(5925):459–462. doi: 10.1038/304459a0. [DOI] [PubMed] [Google Scholar]
  11. Fricks C. E., Icenogle J. P., Hogle J. M. Trypsin sensitivity of the Sabin strain of type 1 poliovirus: cleavage sites in virions and related particles. J Virol. 1985 Jun;54(3):856–859. doi: 10.1128/jvi.54.3.856-859.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Giammarioli A. M., Mackow E. R., Fiore L., Greenberg H. B., Ruggeri F. M. Production and characterization of murine IgA monoclonal antibodies to the surface antigens of rhesus rotavirus. Virology. 1996 Nov 1;225(1):97–110. doi: 10.1006/viro.1996.0578. [DOI] [PubMed] [Google Scholar]
  13. Greenberg H. B., Valdesuso J., van Wyke K., Midthun K., Walsh M., McAuliffe V., Wyatt R. G., Kalica A. R., Flores J., Hoshino Y. Production and preliminary characterization of monoclonal antibodies directed at two surface proteins of rhesus rotavirus. J Virol. 1983 Aug;47(2):267–275. doi: 10.1128/jvi.47.2.267-275.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Hull H. F., Ward N. A., Hull B. P., Milstien J. B., de Quadros C. Paralytic poliomyelitis: seasoned strategies, disappearing disease. Lancet. 1994 May 28;343(8909):1331–1337. doi: 10.1016/s0140-6736(94)92472-4. [DOI] [PubMed] [Google Scholar]
  16. Icenogle J. P., Minor P. D., Ferguson M., Hogle J. M. Modulation of humoral response to a 12-amino-acid site on the poliovirus virion. J Virol. 1986 Oct;60(1):297–301. doi: 10.1128/jvi.60.1.297-301.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kaetzel C. S., Robinson J. K., Chintalacharuvu K. R., Vaerman J. P., Lamm M. E. The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8796–8800. doi: 10.1073/pnas.88.19.8796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kitamura N., Semler B. L., Rothberg P. G., Larsen G. R., Adler C. J., Dorner A. J., Emini E. A., Hanecak R., Lee J. J., van der Werf S. Primary structure, gene organization and polypeptide expression of poliovirus RNA. Nature. 1981 Jun 18;291(5816):547–553. doi: 10.1038/291547a0. [DOI] [PubMed] [Google Scholar]
  19. Kraehenbuhl J. P., Neutra M. R. Molecular and cellular basis of immune protection of mucosal surfaces. Physiol Rev. 1992 Oct;72(4):853–879. doi: 10.1152/physrev.1992.72.4.853. [DOI] [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. Liew F. Y., Russell S. M., Appleyard G., Brand C. M., Beale J. Cross-protection in mice infected with influenza A virus by the respiratory route is correlated with local IgA antibody rather than serum antibody or cytotoxic T cell reactivity. Eur J Immunol. 1984 Apr;14(4):350–356. doi: 10.1002/eji.1830140414. [DOI] [PubMed] [Google Scholar]
  22. Lycke N., Holmgren J. Strong adjuvant properties of cholera toxin on gut mucosal immune responses to orally presented antigens. Immunology. 1986 Oct;59(2):301–308. [PMC free article] [PubMed] [Google Scholar]
  23. Mazanec M. B., Kaetzel C. S., Lamm M. E., Fletcher D., Nedrud J. G. Intracellular neutralization of virus by immunoglobulin A antibodies. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6901–6905. doi: 10.1073/pnas.89.15.6901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mills J., 5th, Van Kirk J. E., Wright P. F., Chanock R. M. Experimental respiratory syncytial virus infection of adults. Possible mechanisms of resistance to infection and illness. J Immunol. 1971 Jul;107(1):123–130. [PubMed] [Google Scholar]
  25. Minor P. D. Antigenic structure of picornaviruses. Curr Top Microbiol Immunol. 1990;161:121–154. doi: 10.1007/978-3-642-75602-3_5. [DOI] [PubMed] [Google Scholar]
  26. Minor P. D., Evans D. M., Ferguson M., Schild G. C., Westrop G., Almond J. W. Principal and subsidiary antigenic sites of VP1 involved in the neutralization of poliovirus type 3. J Gen Virol. 1985 May;66(Pt 5):1159–1165. doi: 10.1099/0022-1317-66-5-1159. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Minor P. D., Schild G. C., Bootman J., Evans D. M., Ferguson M., Reeve P., Spitz M., Stanway G., Cann A. J., Hauptmann R. Location and primary structure of a major antigenic site for poliovirus neutralization. Nature. 1983 Feb 24;301(5902):674–679. doi: 10.1038/301674a0. [DOI] [PubMed] [Google Scholar]
  29. Nomoto A., Omata T., Toyoda H., Kuge S., Horie H., Kataoka Y., Genba Y., Nakano Y., Imura N. Complete nucleotide sequence of the attenuated poliovirus Sabin 1 strain genome. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5793–5797. doi: 10.1073/pnas.79.19.5793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Patriarca P. A., Sutter R. W., Oostvogel P. M. Outbreaks of paralytic poliomyelitis, 1976-1995. J Infect Dis. 1997 Feb;175 (Suppl 1):S165–S172. doi: 10.1093/infdis/175.supplement_1.s165. [DOI] [PubMed] [Google Scholar]
  32. Renegar K. B., Small P. A., Jr Immunoglobulin A mediation of murine nasal anti-influenza virus immunity. J Virol. 1991 Apr;65(4):2146–2148. doi: 10.1128/jvi.65.4.2146-2148.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Roivainen M., Hovi T. Cleavage of VP1 and modification of antigenic site 1 of type 2 polioviruses by intestinal trypsin. J Virol. 1988 Sep;62(9):3536–3539. doi: 10.1128/jvi.62.9.3536-3539.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Roivainen M., Hovi T. Intestinal trypsin can significantly modify antigenic properties of polioviruses: implications for the use of inactivated poliovirus vaccine. J Virol. 1987 Dec;61(12):3749–3753. doi: 10.1128/jvi.61.12.3749-3753.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. SABIN A. B. Pathogenesis of poliomyelitis; reappraisal in the light of new data. Science. 1956 Jun 29;123(3209):1151–1157. doi: 10.1126/science.123.3209.1151. [DOI] [PubMed] [Google Scholar]
  36. Savilahti E., Klemola T., Carlsson B., Mellander L., Stenvik M., Hovi T. Inadequacy of mucosal IgM antibodies in selective IgA deficiency: excretion of attenuated polio viruses is prolonged. J Clin Immunol. 1988 Mar;8(2):89–94. doi: 10.1007/BF00917895. [DOI] [PubMed] [Google Scholar]
  37. Siciński P., Rowiński J., Warchoł J. B., Jarzabek Z., Gut W., Szczygieł B., Bielecki K., Koch G. Poliovirus type 1 enters the human host through intestinal M cells. Gastroenterology. 1990 Jan;98(1):56–58. doi: 10.1016/0016-5085(90)91290-m. [DOI] [PubMed] [Google Scholar]
  38. Wiegers K. J., Wetz K., Dernick R. Molecular basis for linkage of a continuous and discontinuous neutralization epitope on the structural polypeptide VP2 of poliovirus type 1. J Virol. 1990 Mar;64(3):1283–1289. doi: 10.1128/jvi.64.3.1283-1289.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. de Quadros C. A., Andrus J. K., Olive J. M., Guerra de Macedo C., Henderson D. A. Polio eradication from the Western Hemisphere. Annu Rev Public Health. 1992;13:239–252. doi: 10.1146/annurev.pu.13.050192.001323. [DOI] [PubMed] [Google Scholar]

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

RESOURCES