ANTIROTAVIRUS IMMUNOGLOBULIN-A NEUTRALIZES VIRUS IN-VITRO AFTER TRANSCYTOSIS THROUGH EPITHELIAL-CELLS AND PROTECTS INFANT MICE FROM DIARRHEA

Rotaviruses are the major cause of severe diarrhea in infants and youn g children worldwide. Due to their restricted site of replication, i.e ., mature enterocytes, local intestinal antibodies have been proposed to play a major role in protective immunity. Whether secretory immunog lobulin A (IgA) antibodies alone can provide protection against rotavi rus diarrhea has not been fully established, To address this question, a library of IgA monoclonal antibodies (MAbs) previously developed ag ainst different proteins of rhesus rotavirus was used. A murine hybrid oma ''backpack tumor'' model was established to examine if a single MA b secreted onto mucosal surfaces via the normal epithelial transport p athway was capable of protecting mice against diarrhea upon oral chall enge with rotavirus, Of several IgA and IgG MAbs directed against VP6 and VPG of rotavirus, only IgA VP8 MAbs (four of Four) were found to p rotect newborn mice from diarrhea, An Ige MAb recognizing the same epi tope as one of the IgA MAbs tested failed to protect mice from diarrhe a, We also investigated if antibodies could be transcytosed in a biolo gically active form from the basolateral domain to the apical domain t hrough filter-grown Madin-Darby canine kidney (MDCK) tells expressing the polymeric immunoglobulin receptor, Only IgA antibodies with VP8 sp ecificity (four of four) neutralized apically administered virus. The results support the hypothesis that secretory IgA antibodies play a ma jor role in preventing rotavirus diarrhea, Furthermore, the results sh ow that the in vivo and in vitro methods described are useful tools fo r exploring the mechanisms of viral mucosal immunity.