Comparative Studies of the Pathogenesis, Antibody Immune Responses, and Homologous Protection to Porcine and Human Rotaviruses in Gnotobiotic Piglets

  • L. Saif
  • L. Yuan
  • L. Ward
  • T. To
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 412)


Gnotobiotic piglets serve as a useful animal model for studies of rotavirus pathogenesis and immunity. An advantage over laboratory animal models is the prolonged susceptibility of piglets to rotavirus-induced disease, permitting an analysis of cross-protection and active immunity. Studies from our laboratory of the pathogenesis of human rotavirus infections in gnotobiotic piglets have confirmed that villous atrophy is induced in piglets given virulent but not attenuated human rotavirus (Wa strain) and have revealed that factors other than villous atrophy may contribute to the early diarrhea induced. To facilitate and improve rotavirus vaccination strategies, it is important to identify correlates of protective immunity. Comparison of antibody immune responses induced by infection with virulent porcine and human rotaviruses (mimic host response to natural infection) with those induced by live attenuated human rotavirus (mimic attenuated oral vaccines) in the context of homotypic protection has permitted an analysis of correlates of protective immunity. Our results indicate that the magnitude of the immune response is greatest in lymphoid tissues adjacent to the site of viral replication (small intestine). Secondly there was a direct association between the degree of protection induced and the level of the intestinal immune response, with primary exposure to virulent rotaviruses inducing significantly higher numbers of IgA ASC and complete protection against challenge. These studies thus have established basic parameters related to immune protection in the piglet model of rotavirus-induced disease, verifying the usefulness of this model to apply new strategies for the design and improvement of rotavirus vaccines.


Villous Atrophy Antibody Secreting Cell Intestinal Lamina Propria Gnotobiotic Piglet Ohio Agricultural Research 
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  1. Bohl, E.H., Theil, K.W., and Saif, L.J., 1984, Isolation and serotypes of porcine rotaviruses and antigenic comparison with other rotaviruses, J. Clin. Microbiol. 19: 105–111.PubMedGoogle Scholar
  2. Chen, W.K., Campbell, T., VanCott, J., and Saif, L.J., 1995, Enumeration of isotype-specific antibody-secreting cells derived from gnotobiotic piglets inoculated with porcine rotaviruses. Vet. Immunol. Immunopath. 45: 265–284.CrossRefGoogle Scholar
  3. Conner, M.E., Gilger, M.A., Estes, M.K., et al., 1991. Serologic and mucosal immune response to rotavirus infection in the rabbit model. J. Virol. 65: 2562–2571.PubMedGoogle Scholar
  4. DeLeeuw, P.W., Ellens, D.J., Talmon, F.P., Zimmer, G.N., and Kommerij, R., 1980, Rotavirus infections in calves: efficacy of oral vaccination in endemically infected herds. Res. Vet. Sci. 29: 142–147.Google Scholar
  5. Hoblet, K.H., Saif, L.J., Kohler, E.M., Theil, K.W., Bech-Nielsen, S., and Stitzlein, G.A., 1986, Efficacy of an orally administered modified-live porcine-origin rotavirus vaccine against postweaning diarrhea in pigs. Am. J. Vet. Res. 47: 1697–1703.PubMedGoogle Scholar
  6. Hoshino, Y., and Kapikian, A.Z., 1994, Rotavirus vaccine development for the prevention of severe diarrhea in infants and young children. Trends Microbiol. 2: 242–249.CrossRefPubMedGoogle Scholar
  7. Hoshino, T., Saif, L.J., Kang, S.Y., Sereno, M., Chen, W.K., and Kapikian, A.Z., 1995, Identification of group A rotavirus genes associated with virulence of a porcine rotavirus and host range restriction of a human rota-virus in the gnotobiotic piglet model. Virology 209: 274–280.CrossRefPubMedGoogle Scholar
  8. Hoshino, Y., Saif, L.J., Sereno, M.M., Chanock, R.M., and Kapikian, A.Z., 1988, Infection immunity of piglets to either VP3 or VP7 outer capsid protein confers resistance to challenge with a virulent rotavirus bearing the corresponding antigen. J. Viro!. 62: 744–748.Google Scholar
  9. Kapikian, A.Z., and Chanock, R.M., 1990, Rotaviruses. BN Fields, et al. (eds) Virology, Raven Press, New York, pp. 1353–1403.Google Scholar
  10. Kim, Y.B., 1975, Developmental immunity in the piglet. Birth Defects 11: 549.PubMedGoogle Scholar
  11. Mebus, C.A., White, R.G., Bass, E.P., and Twiehaus, M.J., 1973, Immunity to neonatal calf diarrhea virus. J. Am. Vet. Med. Asscoc. 163: 880–883.Google Scholar
  12. Middleton, P.J., Petric, M., and Szymanski, M.T., 1975, Propagation of infantile gastroenteritis virus (orbigroup) in conventional and germfree piglets. Infect. Immun. 12: 1276–1280.PubMedGoogle Scholar
  13. Phillips, R.W., and Tumbleson, M.E., 1986 Models. ME Tumbleson (ed), Swine in Biomedical Research, Plenum Press, New York, pp. 437–440.Google Scholar
  14. Ramig, R., 1988, The effects of host age, virus dose, and virus strain on heterologous rotavirus infection of suckling mice. Micro b. Pathog. 4: 189–202.CrossRefGoogle Scholar
  15. Saif, L.J., Ward, L.A., Rosen, B.I., and To, T.L., 1995, The gnotobiotic piglet as a model for studies of disease pathogenesis and immunity to human rotaviruses. Arch. Viro!. (in press).Google Scholar
  16. Steel, R., and Torres-Medina, A., 1984, Effects of environmental and dietary factors on human rotavirus infection in gnotobiotic piglets. Infect. Immun. 43: 906–911.PubMedGoogle Scholar
  17. Theil, K.W., Bohl, E., Cross, R., Kohler, E., and Agnes, A., 1978, Pathogenesis of porcine rotaviral infection in experimentally inoculated gnotobiotic pigs. Am. J. Vet. Res. 39: 213–220.PubMedGoogle Scholar
  18. Torres-Medina, A., Wyatt, R.G., Mebus, C.A., Underdahl, N.R., and Kapikian, A.Z., 1976, Diarrhea in gnotobiotic piglets caused by the reovirus-like agent of human infantile gastroenteritis. J. Infect. Dis. 133: 22–27.CrossRefPubMedGoogle Scholar
  19. Urasawa, S., Hasegawa, A., Urasawa, T., Taniguchi, K., Wakasugi, F., Suzuki, H., Inouye, S., Pongprot, B., Supawadee, J., Suprasert, S., Rangsiyanond, Tonusin, S., and Yamazi, Y., 1992, Antigenic and genetic analysis of human rotaviruses in Chiang Mai Thailand: Evidence for a close relationship between human and animal rotaviruses. J. Inf. Dis. 166: 227–234.Google Scholar
  20. Van Cott, J., Brim, T., Lunney, J., and Saif, L.J., 1994, Contribution of antibody secreting cells induced in mucosal lymphoid tissues of pigs inoculated with respiratory or enteric strains of coronavirus to immunity against enteric coronavirus challenge. J. lmmunol. 152: 3980–3990.Google Scholar
  21. Wyatt, R.G., James, W.D., Bohl, E.H., Theil, K.W., Saif, L.J., Kalica, A.R., Greenberg, H.B., Kapikian, A.Z., and Chanock, R.M., 1980, Human rotavirus type 2: cultivation in vitro. Science 207: 189–191.CrossRefPubMedGoogle Scholar
  22. Yuan, L., Rosen, B.I., Ward, L.A., Saif, L.J., 1995, Evaluation of systemic and intestinal antibody-secreting cell (ASC) response to human rotavirus in a piglet model of disease. In: Proceedings of the 8th International Congress of Mucosal Immunology, San Diego, California, Abstract.Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • L. Saif
    • 1
  • L. Yuan
    • 1
  • L. Ward
    • 1
  • T. To
    • 1
  1. 1.Food Animal Health Research Program, Department of Veterinary Preventive Medicine, Ohio Agricultural Research and Development CenterThe Ohio State UniversityWoosterUSA

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