A New Gnotobiotic Pig Model of P[6] Human Rotavirus Infection and Disease for Preclinical Evaluation of Rotavirus Vaccines

Figure 1. Arg HRV titers through passaging in neonatal Gn pigs. Data presented are log10 transformed area under the curve (AUC) of virus shedding in feces. Peak virus shedding occurred during passage 6.

Figure 2. Hematoxylin and eosin-stained jejunal lesions in Gn pigs following oral inoculation with Arg P[6] HRV. All tissues were collected at necropsy on PID 2 or 3. (a) Villous damage with fibrin thrombi. (b) Atrophy of the enterocytes. (c) Hemorrhage is present in the lamina propria. (d) Normal jeju num morphology of a mock-infected Gn pig. The magnification of all images is 100×.

Figure 3. Hematoxylin and eosin-stained ileal lesions in Gn pigs following oral inoculation with Arg P[6] HRV. All tissues were collected at necropsy PID 2 or 3. (a–g) or mock (h). Villous blunting/atrophy (a,c–g), hydropic degeneration (a), and lymphoid hyperplasia (a,b,d,e,g) are present. Edema is also present in the lamina propria (d). (h) Normal ileum morphology of a mock-infected Gn pig. The magnification of images (a–g) is 100×, and the magnification for image H is 200×.

Figure 4. Diarrhea from PID 1–7 after inoculation of Gn pigs with different doses of Arg HRV. (A) mean duration of diarrhea, (B) mean cumulative diarrhea scores, (C) AUC of diarrhea, and (D) onset of diarrhea. Error bars represent SEM.

Figure 5. Virus shedding from PID 1–7 after inoculation of Gn pigs with different doses of Arg HRV. (A) duration of fecal shedding, (B) geometric mean peak titer, (C) AUC of fecal shedding, and (D) onset of fecal shedding. A log(10) transformation of data was performed for the geometric mean peak titer and AUC before graphing. Geometric mean peak titers and AUC of fecal shedding were positively correlated with inoculum doses (r = 1, p = 0.08). Error bars represent SEM. ** p < 0.01.

Figure 6. Mean daily virus shedding titer of Gn pigs with different doses of Arg HRV. Log(10) transformed data are presented. All dosage groups shed approximately the same level of the virus as determined by CCIF.