Virus-specific intestinal IFN-γ producing T cell responses induced by human rotavirus infection and vaccines are correlated with protection against rotavirus diarrhea in gnotobiotic pigs

Abstract

We examined rotavirus-specific IFN-γ producing CD4+, CD8+ and CD4+CD8+ T cell responses in gnotobiotic pigs infected with a virulent human rotavirus (VirHRV) or vaccinated with an attenuated (Att) HRV vaccine (AttHRV3x or AttHRV2x) or an AttHRV oral priming and 2/6-virus-like particle (VLP) intranasal boosting (AttHRV-2/6VLP) regimen. In VirHRV infected pigs, HRV-specific IFN-γ producing T cells reside primarily in ileum. AttHRV-2/6VLP induced similar frequencies of intestinal IFN-γ producing T cells as the VirHRV, whereas AttHRV3x or 2x vaccines were less effective. Protection rates against rotavirus diarrhea upon VirHRV challenge significantly correlated (r = 0.97-1.0, p < 0.005) with frequencies of intestinal IFN-γ producing T cells, suggesting their role in protective immunity.

Intranasal P Particle Vaccine Provided Partial Cross-Variant Protection against Human GII.4 Norovirus Diarrhea in Gnotobiotic Pigs

“…In contrast, primary infection with human rotavirus conferred 100% protection against reinfection on Gn pigs upon challenge with 10 5 ID 50 s of the virulent human rotavirus Wa strain (45). Comprehensive T cell immune responses to NoV infection or P particle or VLP vaccination have not been reported previously for humans or Gn pigs.…”

“…ϩ T cells in the intestinal (duodenum, ileum) and systemic (spleen) tissues and blood of Gn pigs. Cells were stimulated in vitro for 17 h and were stained as described previously (44,45). The P particles from VA387 (6 g/ml for the duodenum, ileum, and peripheral blood lymphocytes [PBL] and 12 g/ml for the spleen; the concentrations were optimized in pilot studies) were added to the MNC cultures as a stimulating antigen.…”

“…Virus-specific IFN-␥-producing T cells act as effector cells to eliminate virus-infected cells, and their magnitudes in the small intestine are significantly correlated with protective immunity against rotavirus, another enteric virus (45). NoV-specific effector/memory CD4 ϩ and CD8 ϩ T cells from the NoVPO, P-particle-vaccinated, and control groups at PID 28 and at PCD 7 were detected in intestinal and systemic lymphoid tissues ϩ CD4 ϩ and CD3 ϩ CD8 ϩ T cells in intestinal (duodenum, ileum) and systemic (spleen, PBL) tissues pre-and postchallenge.…”

Dose Effects of LAB on Modulation of Rotavirus Vaccine Induced Immune Responses

“…In contrast, high dose LA reduced the protection conferred by the AttHRV vaccine as indicated by the significantly longer mean duration of virus shedding (3.8 versus 1.3 days) and higher mean cumulative fecal scores compared to the AttHRV only pigs. We reported previously that protection rates against rotavirus diarrhea are correlated with virus-specific intestinal IgA ASC and IFN-producing T cell responses at PID 28 in Gn pigs Yuan et al, 2008). A balanced Th1 and Th2 type response is needed for the optimal protective immunity against rotavirus.…”

“…Although low dose LA further reduced the duration of diarrhea in the AttHRV-vaccinated pigs postchallenge, neither low nor high dose LA significantly altered protection rate against rotavirus challenge (proportions of pigs that were infected and developed diarrhea after challenge). Because virus-specific intestinal IgA ASC responses probably play a more important role in rotavirus protective immunity than the IFN-producing CD8+ T cell responses Yuan et al, 2008), the effect of LA on virus-specific ASC responses also need to be taken into consideration regarding the differences in the protection conferred by the AttHRV vaccine with high or low dose LA. Although the low dose LA enhanced IFN-producing CD8+ T cell responses, it had negative effects on the serum antibody and ASC responses induced by the AttHRV vaccine.…”