Preconceptional Oral Vaccination Prevents Experimental Biliary Atresia in Newborn Mice

Abstract

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.

Aetiology of biliary atresia: what is actually known?

“…The preconditions are such that the strain of mouse, the timing and the dose of virus inoculation must be perfect to achieve BA-like pathology [89,93,94]. Maternal infection during late pregnancy does not induce jaundice, but does prevent the offspring from developing cholestasis following postnatal RRV application [95,96].…”

Prevention of cholestasis in the murine rotavirus-induced biliary atresia model using passive immunization and nonreplicating virus-like particles

“…Other investigators have studied maternal immunization in this model using two currently licensed live RV vaccines as well as live RRV, human RV strain Wa, and a recombinant RV capsid protein VP6 [4, 8, 9]. We also are the first to immunize dams in this model by an intramuscular route rather than the intraperitoneal or oral routes used previously [4, 8, 9]. The route of immunization is important because live virus was detected in the placentas and fetal tissues of dams injected intraperitoneally with live virus [4].…”

“…Other authors have measured RV in the extrahepatic bile ducts or in liver homogenates of RRV-infected pups born to immunized dams [8, 9]. Bondoc et al reported lower levels of RV in the bile ducts of pups born to immunized dams compared with non-immune dams on post-infection days 2 and 7 [8].…”

“…Bondoc et al reported lower levels of RV in the bile ducts of pups born to immunized dams compared with non-immune dams on post-infection days 2 and 7 [8]. In contrast, Turowski et al, found comparable levels of RV in livers of pups born to immunized dams and non-immune control dams [9]. Our finding that healthy pups had lower RV antigen levels than cholestatic pups is consistent with the findings of Bondoc et al [8] and, similarly, suggest that antibody-mediated clearance of RV in healthy RRV-infected pups likely plays a significant role in protection from disease in this model.…”

“…Intraperitoneal immunization of mouse dams in the RV model of BA using live virus, RV capsid protein VP6, or the currently licensed, live, attenuated RV vaccines has been shown to be effective in preventing BA in RRV-infected pups [4, 8, 9]. Maternal immunization (during pregnancy) is an effective and safe means of eliciting or increasing maternal antibody to infectious diseases that can have serious consequences for infants [10].…”