Prevention of Cholestasis in the Murine Rotavirus-Induced Biliary Atresia Model Using Passive Immunization and Nonreplicating Virus-Like Particles

摘要: a b s t r c Biliary atresia is neonatal cholangiopathy of unknown etiology that results in obliteration bile ducts and the primary indication for liver transplant children. A murine model BA, which involves infecting newborn mice with rhesus rotavirus (RRV) leads to development an obstructive cholan- giopathy, has provided assess measures prevent treat BA. We used this mouse RRV-induced BA determine if passive immunization pups using maternal (injection dams non-replicating (RV) virus-like particles (VLPs) or live RRV) injection RV immune serum would protect these RRV-infected neonates from developing (measured cholestasis). Parenteral two formulations VLPs (containing viral proteins 2/6 2/6/7) resulted significant increase antibody, born immunized were protected cholestasis following infection RRV. Serum RV-specific antibody titers ≥400-800 significantly develop- ing cholestasis, trend increasing protection high was observed (p < 0.0001). Cholestatic had lower levels higher 0.01) 0.05) antigen compared healthy pups. Passive transfer low-titer (1600; p high-titer (25,600; prior RRV also them cholestasis. Together, findings indicate passively acquired, neutralizing non-neutralizing attenuates replication protects against disease model. Early reduction load by clearance likely critical determinant