Studies aiming at improvement of inactivated poliovirus vaccine preparations

  • T. Hovi
  • M. Roivainen
  • L. Piirainen


It has been known for some time that inactivated poliovirus vaccine (IPV), including the recently introduced enhanced-potency preparations, in spite of inducing very high levels of neutralizing and probably protecting serum antibodies are inferior to oral poliovirus vaccine (OPV) in preventing intestinal poliovirus infection in the vaccinees. We have proposed that this deficiency, at least as regards type 3 poliovirus, is based on different antigenic sites involved in the induction of antibodies by the two different vaccines because of proteolytic cleavage of a major antigenic site during infection. An approach to circumvent this problem comprises modification of the type 3 component of IPV with trypsin before immunization. A pilot vac cine prepared according to this principle has been obtained and its clinical evaluation will be started soon.


Capsid Protein Antigenic Site Oral Poliovirus Vaccine Poliovirus Type Intact Virus 
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  1. 1.
    von Magnus H ,Pedersen I (1984) Vaccination with inactivated poliovirus vaccine and oral poliovirus vaccine in Denmark. Rev Infec Dis 6(2): 471–474CrossRefGoogle Scholar
  2. 2.
    Slater PE ,Orenstein WA, Morag A, Avni A, Handsher R, Green MS, Cos tin C ,Yarrow A ,Rishpon S ,Havkin O ,Ben-Zvi T, Kew OM, Rey M, Epstein I ,Swartz TA ,Melnick JL (1990) Poliomyelitis outbreak in Israel in 1988: a report with two commentaries. Lancet 335: 1192–1198PubMedCrossRefGoogle Scholar
  3. 3.
    Nkowane BM, Wassilak SGF ,Orenstein WA ,Bart KJ, Schonberger LB, Hinman AR, Kew OM (1987) Vaccine-associated poliomyelitis, United States: 1973–1984. JAMA 254: 1335–1340CrossRefGoogle Scholar
  4. 4.
    Salk D, van Wezel AL, Salk J (1984) Induction of long term immunity to paralytic polio myelitis by use of noninfectious vaccine. Lancet ii: 1317–1321CrossRefGoogle Scholar
  5. 5.
    Onorato IM, Modlin JF, McBean AM, Thoms ML, Losonsky GA, Bernier RH (1991) Mucosal immunity induced by enhanced-potency inactivated and oral polio vaccines. J Infect Dis 163: 1–6PubMedCrossRefGoogle Scholar
  6. 6.
    Ogra PL, Karlzon DT, Righthand F, MacGillivray M (1968) Immunoglobulin response in serum and secretions after immunization with live and inactivated poliovaccine and natural infection. New Engl J Med 279: 893–900PubMedCrossRefGoogle Scholar
  7. 7.
    Svennerholm A-M, Hanson L-Å, Holmgren J, Jalil F, Lindblad BS, Khan SR, Nilsson A, Svennerholm B (1981) Antibody responses to live and killed poliovirus vaccine in the milk of Pakistani and Swedish women. J Infect Dis 143: 707–711PubMedCrossRefGoogle Scholar
  8. 8.
    Hogle JM, Chow M, Filman J (1985) Three dimensional structure of poliovirus at 2.9 A resolution. Science 229: 1358–1365PubMedCrossRefGoogle Scholar
  9. 9.
    Minor PD, Ferguson M, Evans DMA, Almond JW, Icenogle JP (1986) Antigenic structure of poliovirus serotypes 1,2 and 3. J Gen Virol 67: 1283–1291PubMedCrossRefGoogle Scholar
  10. 10.
    Page GS, Mosser AG, Hogle JM, Filman DI, Rueckert RR, Chow M (1988) Three dimensional structure of poliovirus serotype 1 neutralizing determinants. J Virol 62: 1781–1794PubMedGoogle Scholar
  11. 11.
    Huovilainen A, Kinnunen L, Ferguson M, Hovi T (1988) Antigenic variation among 173 strains of type 3 poliovirus ioslated in Finland during the 1984 to 1985 outbreak. J Gen Virol 69: 1941–1948PubMedCrossRefGoogle Scholar
  12. 12.
    Pöyry T, Kinnunen L, KapsenbergJ, Kew O, Hovi T (1990) The type 3 poliovirus strain responsible for the outbreak in Finland in 1984–1985 is genetically related to common Mediterranean strains. J Gen Virol 71: 2535–2541PubMedCrossRefGoogle Scholar
  13. 13.
    GetzoffED, Tanner JA, Lerner RA, Geysen HM (1988) The chemistry and mechanism of antibody binding to protein antigens. Adv Immunol 43: 1–99PubMedCrossRefGoogle Scholar
  14. 14.
    Roivainen M, Närvänen A, Korkolainen M, Huhtala M-L, Hovi T (1991) Antigenic regions of poliovirus type 3/Sabin capsid proteins recognized by human sera in the peptide scanning technique. Virology 180:99–107PubMedCrossRefGoogle Scholar
  15. 15.
    Fricks CE, Icenogle JP, Hogle JM (1985) Trypsin sensitivity of the Sabin strain of type 1 poliovirus: cleavage sites in virions and related particles. J Virol 54: 856–859PubMedGoogle Scholar
  16. 16.
    Icenogle JP, Minor PD, Ferguson M, Hogle JM (1986) Modulation of humoral response to a 12-amino acid site on the poliovirus virion. J Virol 60: 297–301PubMedGoogle Scholar
  17. 17.
    Roivainen M, Montagnon B, Chalumeau H, Murray M, Wimmer E, Hovi T (1990) Improved distribution of antigenic site-specificity of poliovirus neutralizing antibodies induced by a protease-cleaved immunogen in mice. J Virol 64: 559–562PubMedGoogle Scholar
  18. 18.
    Roivainen M, Hovi T (1987) Intestinal trypsin significantly modifies antigenic sites of polioviruses: Implications for the use of inactivated vaccines. J Virol 61: 3749–3753PubMedGoogle Scholar
  19. 19.
    Roivainen M, Hovi T (1988) Cleavage of VP1 and modification of antigenic site 1 of type 2 poliovirus by intestinal trypsin. J Virol 62: 3536–3539PubMedGoogle Scholar
  20. 20.
    Minor PD, Ferguson M, Phillips A, Magrath DI, Huovilainen A, Hovi T (1987) Conserva tion in vivo of protease cleavage sites in antigenic sites of polioviruses. J Gen Virol 68: 1857–1865PubMedCrossRefGoogle Scholar
  21. 21.
    Roivainen M, Huovilainen A, Hovi T (1990) Antigenic modification of polioviruses by host proteolytic enzymes. Arch Virol 111: 115–126PubMedCrossRefGoogle Scholar
  22. 22.
    Hovi T, Roivainen M (1989) Radiometric cytolysis inhibition assay (RACINA): A new rapid test for neutralizing antibodies to intact and trypsin-cleaved poliovirus. J Clin Microbiol 27: 709–715PubMedGoogle Scholar
  23. 23.
    Zhaori G, Sun M, Faden HS, Ogra PL (1989) Nasopharyngeal secretory antibody response to poliovirus type 3 virion proteins exhibit different specificity after immunization with live or inactivated poliovaccines. J Infect Dis 159: 1021–1024CrossRefGoogle Scholar
  24. 24.
    Roivainen M, Piirainen L, Hovi T (1993) Persistence and class-specificity of neutralizing antibody response induced by trypsin-cleaved type 3 poliovirus in mice. Vaccine (in press)Google Scholar

Copyright information

© Springer-Verlag/Wien 1993

Authors and Affiliations

  • T. Hovi
    • 1
  • M. Roivainen
    • 1
  • L. Piirainen
    • 1
  1. 1.Enterovirus LaboratoryNational Public Health InstituteHelsinkiFinland

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