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Efficacy of rotavirus-like particle vaccines and pathogenesis of human rotavirus evaluated in a gnotobiotic pig model

Azevedo, Marli S. P.

Abstract Details

2005, Doctor of Philosophy, Ohio State University, Veterinary Preventive Medicine.
Despite great efforts to understanding the pathogenicity of and protective immunity to rotavirus infection, a definite correlate of protective immunity after vaccination has not been identified. The main goals of this dissertation were: to identify correlates of protective immunity after vaccination with virus-like particle (VLP) vaccines; to examine the extent of extraintestinal spread of rotavirus; and to delineate comprehensively the cytokine profiles induced by virulent (Vir) and attenuated (Att) rotaviruses. After oral priming with AttHRV and intranasal boosting with 2/6VLP+mutant E. coli heat labile toxin, only IgA antibody titers in serum were highly correlated with IgA antibody titers in the intestines, indicating that serum IgA antibody titer is a reliable indicator of intestinal antibody responses and protection. Pigs inoculated with AttHRV shed virus mainly nasally, whereas pigs inoculated with VirHRV developed diarrhea, shed virus nasally and rectally and had viremia. This study provided new evidence that VirHRV causes transient viremia and upper respiratory tract infection in addition to gastrointestinal infection in Gn pigs. After VirHRV infection, a significantly higher percentage of pigs had IFN-gamma and IL-10 responses in serum, with significantly higher and prolonged IFN-gamma responses in the VirHRV compared to AttHRV pigs. This observation coincides with the diarrhea and viremia induced by the VirHRV, but not the AttHRV. These data further indicate a balanced Th1/Th2 response during rotavirus infection, but with higher cytokine levels early after infection with VirHRV compared to AttHRV. These findings have improved our understanding of rotavirus pathogenesis, immunogenicity and correlates of protection.
Linda Saif (Advisor)
298 p.

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Citations

  • Azevedo, M. S. P. (2005). Efficacy of rotavirus-like particle vaccines and pathogenesis of human rotavirus evaluated in a gnotobiotic pig model [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1110288856

    APA Style (7th edition)

  • Azevedo, Marli. Efficacy of rotavirus-like particle vaccines and pathogenesis of human rotavirus evaluated in a gnotobiotic pig model. 2005. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1110288856.

    MLA Style (8th edition)

  • Azevedo, Marli. "Efficacy of rotavirus-like particle vaccines and pathogenesis of human rotavirus evaluated in a gnotobiotic pig model." Doctoral dissertation, Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1110288856

    Chicago Manual of Style (17th edition)