Natural evolution of oral vaccine poliovirus strains

  • R. Crainic
  • M. Furione
  • D. Otelea
  • S. Guillot
  • J. Balanant
  • A. Aubert-Combiescu
  • M. Combiescu
  • A. Candrea


The oral poliovirus vaccine, prepared with attenuated Sabin strains, is widely used to efficiently control poliomyelitis. One problem raised by its use is the occurrence of a certain, very few, number of vaccine-associated paralytic cases. This is due to the genetic instability of the three component viruses, mainly type 2 and type 3, upon multiplication in humans. Point mutations in critical nucleotide positions are generally accepted as one mechanism of reversion towards neurovirulence of Sabin strains. In this paper we present evidence that intermolecular recombi nation, possibly in combination with mutation, may also play a role in the loss of attenuation of vaccine polioviruses.


Oral Poliovirus Vaccine Inactivate Poliovirus Vaccine Paralytic Poliomyelitis Wild Poliovirus Sabin Strain 
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  1. 1.
    Agut H, Kean KM, Belloq C, Fichot O, Girard M (1987) Intratypic recombination of polioviruses: evidence for multiple crossing-over sites on the viral genome. J Virol 61: 1722–1725PubMedGoogle Scholar
  2. 2.
    Almond J (1987) The attenuation of neurovirulence. Ann Rev Microbiol 41: 153–180CrossRefGoogle Scholar
  3. 3.
    Assaad F, Ljungars-Esteves K (1984) World overview of poliomyelitis: Regional patterns and trends. Rev Infect Dis 6 [Suppl 2]: S302–S307PubMedCrossRefGoogle Scholar
  4. 4.
    Balanant J, Guillot S, Gandrea A, Delpeyroux F, Crainic R (1991) The natural genomic variability of poliovirus analyzed by a restriction fragment length polymorphism assay. Virology 184: 645–654PubMedCrossRefGoogle Scholar
  5. 5.
    Blondel B, Akacem O, Crainic R, Couillin P, Horodniceanu F (1983) Detection by monoclonal antibodies of an antigenic determinant critical for poliovirus neutralization present on VP1 and on heat inactivated virions. Virology 126: 707–710PubMedCrossRefGoogle Scholar
  6. 6.
    Cammack N, Phillips A, Dunn G, Patel V, PD M (1989) Intertypic genomic rearrange ments of poliovirus strains in vaccinees. Virology 167: 507–514Google Scholar
  7. 7.
    Christodoulou C ,Colbére-Garapin F, Macadam A, Taffs LF, Marsden S, Minor PD, Horaud F (1990) Mapping of mutations associated with neurovirulence in monkeys infected with Sabin 1 poliovirus revertants selected at high temperature. J Virol 64: 4922–4929PubMedGoogle Scholar
  8. 8.
    Chumakov KM, Powers LB, Noonan KE, IB R, Levenbook IS (1991) Correlation between amount of virus with altered nucleotide sequence and the monkey test for acceptability of oral poliovirus vaccine. Proc Natl Acad Sci USA 88: 199–203PubMedCrossRefGoogle Scholar
  9. 9.
    Crainic R, Couillin P, Blondel B, Cabau N, Boué A, Horodniceanu F (1983) Natural variation of poliovirus neutralization epitopes. Infect Immun 41: 1217–1225PubMedGoogle Scholar
  10. 10.
    Da Silva EE, Pallansch MA, Holloway BP, Oliveira C, Kew OM (1991) Oligonucleotide probe for the specific detection of the wild poliovirus type 1 and 3 endemic in Brazil. Intervirology 32: 149–159PubMedGoogle Scholar
  11. 11.
    De Quadros CA, AndrusJK, Olive JM (1991) Eradication of poliomyelitis: progress in the Americas. Pediatr Infect Dis 10: 222–229CrossRefGoogle Scholar
  12. 12.
    Domingo E, Martinez-Salas E, Sobrino J, de la Torre JC, Portella A, Ortin J, Lopez-Galindez C, Perez-Brena P, Villaneuva N NR, VandePol D, Steinhauer D, ND, Holland JJ (1985) The quasispecies (extremely heterogeneous) nature of viral RNA genome population:biological relevance -a review. Gene 40: 1–8PubMedCrossRefGoogle Scholar
  13. 13.
    EPI (1989) Poliomyelitis in 1986, 1987 and 1988. Wkly Epidemiol Rec 64:273–285Google Scholar
  14. 14.
    Evans DMA, Dunn G, Minor PD, Schild GC, Cann AJ (1985) Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome. Nature 314: 548–550PubMedCrossRefGoogle Scholar
  15. 15.
    Ferguson M, Qi Y-H, Minor PD, Magrath DI, Spitz M, Schild GC (1982) Monoclonal antibodies specific for the Sabin vaccine strains of poliovirus 3. Lancet ii: 122–124CrossRefGoogle Scholar
  16. 16.
    Hirst G (1982) Genetic recombination with Newcastle disease virus, poliovirus and influenza. Cold Spring Harbor Symp Quant Biol 27: 303–309Google Scholar
  17. 17.
    Hogle JM, Chow M, Filman DJ (1985) Three dimensional structure of poliovirus at 2.9 A resolution. Science 229: 1358–1365PubMedCrossRefGoogle Scholar
  18. 18.
    Holland JJ, Spindler K, Horodyski F, Grabau E, Nichol S, Vandepol S (1982) Rapid evolution of RNA genomes. Science 215: 1577–1585PubMedCrossRefGoogle Scholar
  19. 19.
    Hovi T (1991) Remaining problems before eradication of poliomyelitis can be accom plished. Prog Med Virol 38: 69–95PubMedGoogle Scholar
  20. 20.
    Hughes PJ, North C, Minor PD, Stanway G (1989) The nucleotide sequence of coxsackievirus A21. J Gen Virol 70:2943–2952PubMedCrossRefGoogle Scholar
  21. 21.
    Kawamura N, Kohara M, Abe S, Komatsu T, Tago K, Arita M, Nomoto A (1989) Determinants in the 5’ non-coding region of poliovirus Sabin 1 RNA that influence the attenuated phenotype. J Virol 63: 1302–1309PubMedGoogle Scholar
  22. 22.
    Kew O, De L Yang, CF, Nottay B, Pallansch M (1992) The role of virologic surveillance in the global initiative to eradicate poliomyelitis. In: Kurstak E (ed. inchief), Applied Virology Research, Vol. 2. New-York, pp. 215–246Google Scholar
  23. 23.
    Kew OM, Nottay BK (1984) Evolution of oral poliovirus vaccine strain in humans occurs by both mutation and intermolecular recombination. In: R Chanock RL (ed) Modern approach to vaccines. New-York, pp 357–362Google Scholar
  24. 24.
    Kew OM, Nottay BK, Rico-Hesse RR, Pallansch MA (1990) Molecular epidemiology of wild poliovirus transmission. Applied Virol Res 2: 199–221Google Scholar
  25. 25.
    Kinnunen L, Huovilainen A, Pöyry T, Hovi T (1990) Rapid molecular evolution of wild type 3 poliovirus during infection in individual hosts. J Gen Virol 71: 317–324PubMedCrossRefGoogle Scholar
  26. 26.
    Kitamura N, Semler B, Rothberg PG, Larsen GR, CJ Adler, AJ Dorner, Emini EA, Hanecak R, Lee JJ, van der Werf S, Anderson CW, Wimmer E (1981) Primary structure, gene organization and polypeptide expression of poliovirus RNA. Nature 291: 547–553PubMedCrossRefGoogle Scholar
  27. 27.
    Kohara M, Omata T, Kameda A, Semler BL, Itoh H, Wimmer E, Nomoto A (1985) In vitro phenotypic markers of a poliovirus recombinant constructed from infectious cDNA clones of the neurovirulent Mahoney strain and the attenuated Sabin 1 strain. J Virol 53: 786–792PubMedGoogle Scholar
  28. 28.
    Koike G, Taya C ,Kurata T, Abe S, Ise I, Yonekawa H, Nomoto A (1991) Transgenic mice susceptible to poliovirus. Proc Natl Acad Sci USA 88: 951–955PubMedCrossRefGoogle Scholar
  29. 29.
    Lai MMC (1992) RNA recombination in animal and plant viruses. Microbiol Rev 56:61–79PubMedGoogle Scholar
  30. 30.
    Lipskaia GY, Muzychenko AR, Kutitova OK, Maslova SV, Equestre M, Drozdov SG, Perez-BercofTR, Agol VI (1991) Frequent isolation of intertypic poliovirus recombinants with serotype 2 specificity from vaccine-associated polio cases. J Med Virol 35: 290–296CrossRefGoogle Scholar
  31. 31.
    Macadam AJ, Pollard SR, Ferguson G, Dunn G, Skuce R, Almond JW, Minor PD (1991) The 5’ noncoding region of the type 2 poliovirus vaccine strain contains determi nants of attenuation and temperature sensitivity. Virology 181: 451–458PubMedCrossRefGoogle Scholar
  32. 32.
    Melnick JL (1990) Enteroviruses: polioviruses, coxsackieviruses, echoviruses and newer enteroviruses. In: Fields BN, Knipe DM, Chanock RM, Melnick J, Roizman B, Shope RE (eds) Virology. New-York, pp 739–794Google Scholar
  33. 33.
    Minor PD, Dunn G, Evans DMA, Margrath DI, John A, Howlett J, Phillips D, Westrop G, Warcham K, Almond JW, HogleJM (1989) The temperature sensitivity of the Sabin type 3 vaccine strain of poliovirus: molecular and structural effects of a mutation in the capsid protein VP3. J Gen Virol 70: 117–1125CrossRefGoogle Scholar
  34. 34.
    Minor PD, John A, Ferguson M, Icenogle JP (1986) Antigenic and molecular evolution of the vaccine strain of type 3 poliovirus during the period of excretion by primary vaccine. J Gen Virol 67: 693PubMedCrossRefGoogle Scholar
  35. 35.
    Nakano JH, Hatch MH, Thieme ML, Nottay B (1978) Parameters for differentiating vaccine-derived and wild poliovirus strains. Prog med Virol 24: 178–206PubMedGoogle Scholar
  36. 36.
    Nkowane BM, Wassilak SGF, Orenstein WA, Bart KJ, Schonberger LB, Hinman AR, Kew OM (1987) Vaccine-associated paralytic poliomyelitis: United States: 1973 through 1984. Jama 257: 1335–1340PubMedCrossRefGoogle Scholar
  37. 37.
    Nomoto A, Omatoa T, Toyoda H, Kuge S, Horie H, Kataoka Y, Genba Y, Nakano Y, Imura N (1982) Complete nucleotide sequence of the attenuated poliovirus Sabin 1 strain genome. Proc Natl Acad Sci USA 79: 5793–5797PubMedCrossRefGoogle Scholar
  38. 38.
    Nottay BK, Kew OM, Hatch MH, Heyward JT, Obijeski JF (1981) Molecular variation of type 1 vaccine-related and wild polioviruses during replication in humans. Virology 108: 405–423PubMedCrossRefGoogle Scholar
  39. 39.
    Omata T, Kohara M, Kuge S (1986) Genetic analysis of the attenuation phenotype of poliovirus type 1. J Gen Virol 58: 348–358Google Scholar
  40. 40.
    Osterhaus ADME, Van Wezel A, Uztdehaag FGCM, Hazendonkk TG, Van Ästen JAAM, Van Steenis B (1981) Monoclonal antibodies to poliovirus: production of specific monoclonal antibodies to the Sabin vaccine strains. Intervirology 16: 218–244PubMedCrossRefGoogle Scholar
  41. 40a.
    Otelea D, Guillot S, Furione M, Aubert-Combiescu A, Balanant J, Candrea A, and Crainic R (1992) Genomic modifications in naturally occurring neurovirulent revertants of Sabin 1 polioviruses. Develop Biol Standard, 78: 33–38.Google Scholar
  42. 41.
    Palmenberg AC (1989) Sequence alignments of picornaviral capsid proteins. In: Semler BL, Ehrenfeld E (ed) Washington DC, pp 211–241Google Scholar
  43. 42.
    Racaniello VR (1988) Poliovirus neurovirulence. Adv Virus Res 34: 217–246PubMedCrossRefGoogle Scholar
  44. 43.
    Rico-Hesse R, Pallansch MA, Nottay BK, Kew OM (1987) Geographic distribution of wild poliovirus type 1 genotypes. Virology 160: 311–322PubMedCrossRefGoogle Scholar
  45. 44.
    Rossamann MG, Arnold E, Erickson JW, Frankenberger EA, Griffith JP, Hecht HJ, Johnson JE, Kamer G, Luo M, Mosser AG, Rueckert RR, Sherry B, Vriend G (1985) Structure of a human common cold virus and functional relationship to other picornaviruses. Nature 317: 145–153CrossRefGoogle Scholar
  46. 45.
    Rueckert RR (1985) Picornaviruses and their replication. In: Fields BN (ed) Virology. New-York, pp 705–738Google Scholar
  47. 46.
    Ryan MD, Jenkins O, Hughes PJ, Brown A, Knowles NJ, Booth D, Minor PD, Almond JW (1990) The complete nucleotide sequence of enterovirus type 70: relationships with other Picornaviridae. J Gen Virol 71: 2291–2299PubMedCrossRefGoogle Scholar
  48. 47.
    Sabin AB (1985) Oral poliovirus vaccine: History of its development and use and current challenge to eliminate poliomyelitis from the world. J Infect Dis 151: 420–436PubMedCrossRefGoogle Scholar
  49. 48.
    Sabin AB, Boulger LR (1973) History of Sabin attenuated poliovirus oral live vaccine strains. J Biol Standard 1: 115–118CrossRefGoogle Scholar
  50. 49.
    Toyoda H, Kohara M, Kataoka Y, Suganuma T, Omata T, Imura N, Nomoto A (1984) Complete nucleotide sequences for all three poliovirus serotype genomes: implication for genetic relationship, gene function and antigenic determinants. J Mol Biol 174: 561–585PubMedCrossRefGoogle Scholar
  51. 50.
    Van Wezel AL, Hazendonk AG (1979) Intratypic serodifferentiation of poliomyelitis strains by strain-specific antisera. Intervirology 11: 2–8PubMedCrossRefGoogle Scholar
  52. 51.
    Villaverde A, Martinez-Salas E, Domingo E (1988) 3D gene of foot-and-mouth disease virus conservation by covergence of average sequences. Gene 23: 185–194Google Scholar
  53. 52.
    Ward CD, Stoekes MA, Flanegan JB (1988) Direct measurement of the poliovirus RNA polymerase error frequency in vitro. J Virol 62: 558–562PubMedGoogle Scholar
  54. 53.
    WHO (1981) Markers of poliovirus strains isolated from cases temporally associated with the use of live poliovirus vaccine. J Biol Standard 9: 163–184CrossRefGoogle Scholar
  55. 54.
    WHO (1990) Expanded programme on immunization. Progress towards the eradicating poliomyelitis from the Americas. Wkly Epidem Rec 65: 361 -364Google Scholar
  56. 55.
    WHO (1992) Expanded programme on immunization. Global Advisory Group. Wkly Epidem Rec 67: 9–31Google Scholar
  57. 56.
    WHO (1992) Expanded Programme on Immunization. Poliomyelitis in 1988,1989 and 1990. Wkly Epidem Rec 67: 113–120Google Scholar
  58. 57.
    Wright PF, Kim-Farley RJ, de Quadros GA, Robertson SE, McN Scott R, Ward NA, Henderson RH (1991) Strategies for the global eradication of poliomyelitis by the year 2000. N Engl J Med 325: 1774–1779PubMedCrossRefGoogle Scholar
  59. 58.
    Yang CF, De L, Holloway BP, Pallansch MA, Kew OM (1991) Detection and identification of vaccine-related polioviruses by polymerase chain reaction. Virus Res. 20: 159–179PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1993

Authors and Affiliations

  • R. Crainic
    • 1
  • M. Furione
    • 1
  • D. Otelea
    • 1
  • S. Guillot
    • 1
  • J. Balanant
    • 1
  • A. Aubert-Combiescu
    • 2
  • M. Combiescu
    • 2
  • A. Candrea
    • 1
  1. 1.Unité de Virologie MédicaleInstitut PasteurParisFrance
  2. 2.Cantacuzino InstituteBucharestRomania

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