Jennerian and modified Jennerian approach to vaccination against rotavirus diarrhea using a quadrivalent rhesus rotavirus (RRV) and human-RRV reassortant vaccine

  • A. Z. Kapikian
  • Y. Hoshino
  • R. M. Chanock
  • I. Perez-Schael
Part of the Archives of Virology book series (ARCHIVES SUPPL, volume 12)


Rotaviruses are the single most important cause of severe diarrhea of infants and young children world-wide. Deaths from rotavirus diarrhea occur infrequently in developed countries; however, in developing countries, rotaviruses are estimated to cause over 870 000 deaths in the under five-year age group. There is, therefore, a vital need for a vaccine to prevent severe rotavirus diarrhea in infants and young children. The most extensively evaluated strategy for rotavirus vaccination has been the “Jennerian” approach in which an antigenically related rotavirus strain from an animal host (bovine or simian [rhesus monkey]) is used as the immunogen to induce protection against the four epidemiologically important group A human rotavirus serotypes. These orally administered vaccines were safe and immunogenic but had only limited success because serotype-specific immunity was not induced consistently in the under six-month age group. Therefore, a modified “Jennerian” approach was adopted with the goal of attaining broader antigenic coverage. In this approach, four serotypes are combined to form a quadrivalent vaccine comprised of: (i) rhesus rotavirus (RRV) which provides coverage for VP7 serotype 3, and (ii) three human-RRV reassortants each with ten RRV genes and a single human rotavirus gene that encodes VP7 serotype 1, 2, or 4 specificity. This modified “Jennerian” approach appears to be quite promising in preventing severe diarrhea in field trials. However, if this approach fails to yield an optimal level of protection consistently, additional modified “Jennerian” strategies are under development that consider not only human rotavirus VP7 but also human rotavirus VP4, the other outer capsid protein. In addition, a non- “Jennerian” approach includes the development of cold-adapted human rotavirus strains or cold-adapted human rotavirus reassortants as vaccine candidates.


Quadrivalent Vaccine Outer Capsid Protein Monovalent Vaccine Reassortant Vaccine Gnotobiotic Calf 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Bernstein DI, Glass RI, Rogers G, Davidson BL, Sack DA, for the U.S. Rotavirus Vaccine Efficacy Group (1995) Evaluation of rhesus rotavirus monovalent and tetravalent reassortant vaccines in US children. JAMA 273: 1191–1196PubMedCrossRefGoogle Scholar
  2. 2.
    Bishop RF, Barnes GL, Cipriani E, Lund JS (1983) Clinical immunity after neonatal rotavirus infection. A prospective longitudinal study in young children. N Engl J Med 309: 72–76PubMedCrossRefGoogle Scholar
  3. 3.
    Flores J, Perez-Schael I, Blanco M, White L, Garcia D, Vilar M, Cunto W, Gonzalez R, Urbina C, Boher J, Mendez M, Kapikian AZ (1990) Comparison of reactogenicity and antigenicity of M37 rotavirus vaccine and rhesus-rotavirus-based quadrivalent vaccine. Lancet 336: 330–334PubMedCrossRefGoogle Scholar
  4. 4.
    Flores J, Perez-Schael I, Blanco M, Rojas AM, Alfonzo E, Crespo I, Cunto W, Pittman A, Kapikian AZ (1993) Reactogenicity and immunogenicity of a high-titered rhesus rotavirus-based quadrivalent rotavirus vaccine. J Clin Microbiol 31: 2439–2445PubMedGoogle Scholar
  5. 5.
    Ho M-S, Glass RI, Pinsky PF, Young-Okoh N, Sappenfield WM, Buehler JW, Gunter N, Anderson LJ (1988) Diarrheal deaths in American children. Are they preventable?. JAMA 260: 3281–3285PubMedCrossRefGoogle Scholar
  6. 6.
    Hoshino Y, Kapikian AZ (1994) Rotavirus vaccine development for the prevention of severe diarrhea in infants and young children. Trends Microbiol 2: 242–249PubMedCrossRefGoogle Scholar
  7. 7.
    Hoshino Y, Kapikian AZ, Chanock RM (1994) Selection of cold-adapted mutants of human rotaviruses that exhibit various degrees of growth restriction in vitro. J Virol 68: 7598–7602PubMedGoogle Scholar
  8. 8.
    Hoshino Y, Saif L, Kang S-Y, Sereno MM, Chen W-K, Kapikian AZ (1995) Identification of group A rotavirus genes associated with virulence of a porcine rotavirus and host range restriction of a human rotavirus in the gnotobiotic piglet model. Virology 209: 274–280PubMedCrossRefGoogle Scholar
  9. 9.
    Institute of Medicine (1986) Prospects for immunizing against rotavirus. In: New Vaccine Development. Establishing Priorities. Diseases of Importance in the United States, vol 1. National Academy Press, Washington, DC, pp 410–423Google Scholar
  10. 10.
    Institute of Medicine (1986) The prospects for immunizing against rotavirus. In: New Vaccine Development. Establishing Priorities. Diseases of Importance in Developing Countries, vol 2. National Academy Press, Washington, DC, pp 308–316Google Scholar
  11. 11.
    Kapikian AZ (1994) Jennerian and modified Jennerian approach to vaccination against rotavirus diarrhea in infants and young children: an introduction. In: Kapikian AZ (ed) Viral Infections of the Gastrointestinal Tract. Marcel Dekker, New York, pp 409–417Google Scholar
  12. 12.
    Kapikian AZ (1994) Rhesus rotavirus-based human rotavirus vaccines and observations on selected non-Jennerian approaches to rotavirus vaccination. In: Kapikian AZ (ed) Viral Infections of the Gastrointestinal Tract. Marcel Dekker, New York, pp 443–470Google Scholar
  13. 13.
    Kapikian AZ, Chanock RM (1996) Rotaviruses. In: Fields BN, Knipe DM, Howley PM, Chanock RM, Melnick JL, Monath TP, Roizman B, Straus SE (eds) Virology. Lippin-cott-Raven Publishers, Philadelphia, pp 1657–1708Google Scholar
  14. 14.
    Kapikian AZ, Cline WL, Kim HW, Kalica AR, Wyatt RG, Van Kirk DH, Chanock RM, James HD Jr, Vaughn AL (1976) Antigenic relationships among five reovirus-like (RVL) agents by complement-fixation (CF) and development of new substitute CF antigens for the human RVL agent of infantile gastroenteritis. Proc Soc Exp Biol Med 152: 535–539PubMedGoogle Scholar
  15. 15.
    Kapikian AZ, Hoshino Y, Flores J, Midthun K, Glass RI, Nakagomi O, Nakagomi T, Chanock RM, Potash L, Levine MM, Dolin R, Wright PF, Belshe RE, Anderson EL, Vesikari T, Gothefors L, Wadell G, Perez-Schael I (1986) In: Holmgren J, Lindberg A, Mollby R (eds) Development of Vaccines and Drugs Against Diarrhea. 11th Nobel Conference, Stockholm 1985. Student litteratur, Lund, Sweden, pp 192–214Google Scholar
  16. 16.
    Kapikian AZ, Vesikari T, Ruuska T, Madore HP, Christy C, Dolin R, Flores J, Green KY, Davidson BL, Gorziglia M, Hoshino Y, Chanock RM, Midthun K, Perez-Schael I (1992) An update on the “Jennerian” and modified “Jennerian” approach to vaccination of infants and young children against rotavirus diarrhea. Adv Exp Med Biol 327: 59–69PubMedCrossRefGoogle Scholar
  17. 17.
    Kapikian AZ, Wyatt RG, Levine MM, Black RE, Greenberg HB, Flores J, Kalica AR, Hoshino Y, Chanock RM (1983) Studies in volunteers with human rotaviruses. Dev Biol Stand 53: 209–218PubMedGoogle Scholar
  18. 18.
    Madore HP, Christy C, Pichichero M, Long C, Pincus P, Vosefsky P, Kapikian AZ, Dolin R, Elmwood, Panorama, and Westfall Pediatric Groups (1992) Field trial of rhesus rotavirus or human-rhesus reassortant vaccine of VP7 serotype 3 or 1 specificity in infants. J Infect Dis 166: 235–243PubMedCrossRefGoogle Scholar
  19. 19.
    Mattion NM, Cohen J, Estes MK (1994) The rotavirus proteins. In: Kapikian AZ (ed) Viral Infections of the Gastrointestinal Tract. Marcel Dekker, New York, pp 169–249Google Scholar
  20. 20.
    Midthun K, Greenberg HB, Hoshino Y, Kapikian AZ, Wyatt RG, Chanock RM (1985) Reassortant rotaviruses as potential live rotavirus vaccine candidates. J Virol 53: 949–954PubMedGoogle Scholar
  21. 21.
    Midthun K, Hoshino Y, Kapikian AZ, Chanock RM (1986) Single gene substitution rotavirus reassortants containing the major neutralization protein (VP7) of human rotavirus serotype 4. J Clin Microbiol 24: 822–826PubMedGoogle Scholar
  22. 22.
    Perez-Schael I, Garcia D, Gonzalez M, Gonzalez R, Daoud N, Perez M, Cunto W, Kapikian AZ, Flores J (1990) Prospective study of diarrheal diseases in Venezuelan children to evaluate the efficacy of rhesus rotavirus vaccine. J Med Virol 30: 219–229PubMedCrossRefGoogle Scholar
  23. 23.
    Prasad BV, Burns JW, Marietta E, Estes MK, Chiu W (1990) Localization of VP4 neutralization sites in rotavirus by three-dimensional cryo-electron microscopy. Nature 343: 476–479PubMedCrossRefGoogle Scholar
  24. 24.
    Rennels MB, Glass RI, Dennehy PH, Bernstein DI, Pichichero ME, Zito ET, Mack ME, Davidson BL, Kapikian AZ, for the United States Rotavirus Efficacy Group (1996) Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines-report of the national multicenter trial. Pediatrics 97: 7–13PubMedGoogle Scholar
  25. 25.
    Vesikari T, Ruuska T, Green KY, Flores J, Kapikian AZ (1992) Protective efficacy against serotype 1 rotavirus diarrhea by live oral rhesus-human reassortant rotavirus vaccines with human rotavirus VP7 serotype 1 or 2 specificity. Pediatr Inf Dis J 11: 535–542CrossRefGoogle Scholar
  26. 26.
    Vesikari T, Ruuska T, Kouvu HP, Green KY, Flores J, Kapikian AZ (1991) Evaluation of the M37 human rotavirus vaccine in 2-to 6-month old infants. Pediatr Inf Dis J 10: 912–917Google Scholar
  27. 27.
    Wallace RE, Vasington PJ, Petricciani JC, Hopps HE, Lorenz DE, Kadanka Z (1973) Development of a diploid cell line from fetal rhesus monkey lung for virus vaccine production. In Vitro 8: 323–332Google Scholar
  28. 28.
    World Health Organization Scientific Working Group (1980) Rotavirus and other viral diarrheas. Bull WHO 58: 183–198Google Scholar
  29. 29.
    Wyatt RG, Kapikian AZ, Hoshino Y, Flores J, Midthun K, Greenberg HB, Glass RI, Askaa J, Levine MM, Black RE, Clements ML, Potash L, London WT (1985) In Control and Eradication of Infectious Diseases. An International Symposium PAHO copublication series no. 1. Washington, DC, Pan American Health Organization, pp 17–28Google Scholar
  30. 30.
    Wyatt RG, Mebus CA, Yolken RH, Kalica AR, James HD Jr, Kapikian AZ, Chanock RM (1979) Rota viral immunity in gnotobiotic calves: Heterologous resistance to human virus induced by bovine virus. Science 203: 548–550PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1996

Authors and Affiliations

  • A. Z. Kapikian
    • 1
  • Y. Hoshino
    • 1
  • R. M. Chanock
    • 1
  • I. Perez-Schael
    • 2
  1. 1.Laboratory of Infectious Diseases, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaUSA
  2. 2.Central University of VenezuelaCaracasVenezuela

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