Preconceptional Oral Vaccination Prevents Experimental Biliary Atresia in Newborn Mice

Abstract

Introduction: Biliary atresia (BA) in humans resembles BA induced in Balb/c-mice by Rhesus Rotavirus (RRV). In mice, susceptibility to BA is ascribed to the lack of maternally derived immune protection. This study investigated whether vaccination of dams against RRV protected their offspring from developing BA.

Materials and Methods: Before mating, female mice were vaccinated orally with RotaTeq^® or Rotarix^®. Pups (n=243) from both test groups and a control group were intraperitoneally infected with RRV. Sacrifice of the animals was scheduled for days 7, 14 and 21 after infection. Then, gross and mircoscopia findings of the liver and the hepatoduodenal ligament gave evidence of BA, and hepatic viral load was tested by virus-specific real-time PCR, as well as plaque forming units.

Results: Two weeks after infection, the incidence of cholestasis was 100% in controls, 77% in pups of RotaTeq^®-vaccinated dams, and 56% in pups of Rotarix^®-vaccinated dams. However, in contrast to controls (incidence of BA: 82%) most pups in the test groups recovered (incidence of BA in pups of RotaTeq^®-vaccinated dams 11%; incidence of BA in pups of Rotarix^®-vaccinated dams 3%). Hepatic viral load was identical at various time-points in all pups, suggesting that differences in RRV clearance did not underlie this effect.

Conclusion: In this mouse model, oral vaccination with RotaTeq^® and Rotarix^® prevented most RRV-induced BA. This provides a new approach to a better understanding of both the pathomechanism of BA development and the capabilities of the innate immune system. It also suggests a first approach for prophylaxis against BA.

Key words

biliary atresia - mouse model - rhesus rotavirus - vaccination - prevention

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