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J Virol, April 1998, p. 2708-2714, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Antirotavirus Immunoglobulin A Neutralizes Virus In Vitro after Transcytosis through Epithelial Cells and Protects Infant Mice from Diarrhea

Franco M. Ruggeri,1 Kari Johansen,2 Gino Basile,1 Jean-Pierre Kraehenbuhl,3,4 and Lennart Svensson2,*

Laboratorio di Ultrastrutture, Istituto Superiore di Sanitá, 00161 Rome, Italy1; Department of Virology, Swedish Institute for Infectious Disease Control, Karolinska Institute, 105 21 Stockholm, Sweden2; and Institute of Biochemistry, University of Lausanne, 1015 Lausanne,3 and the Swiss Institute for Experimental Cancer Research, 1066 Epalinges,4 Switzerland

Received 21 July 1997/Accepted 12 December 1997

Rotaviruses are the major cause of severe diarrhea in infants and young 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 immunoglobulin A (IgA) antibodies alone can provide protection against rotavirus diarrhea has not been fully established. To address this question, a library of IgA monoclonal antibodies (MAbs) previously developed against different proteins of rhesus rotavirus was used. A murine hybridoma "backpack tumor" model was established to examine if a single MAb secreted onto mucosal surfaces via the normal epithelial transport pathway was capable of protecting mice against diarrhea upon oral challenge with rotavirus. Of several IgA and IgG MAbs directed against VP8 and VP6 of rotavirus, only IgA VP8 MAbs (four of four) were found to protect newborn mice from diarrhea. An IgG MAb recognizing the same epitope as one of the IgA MAbs tested failed to protect mice from diarrhea. We also investigated if antibodies could be transcytosed in a biologically active form from the basolateral domain to the apical domain through filter-grown Madin-Darby canine kidney (MDCK) cells expressing the polymeric immunoglobulin receptor. Only IgA antibodies with VP8 specificity (four of four) neutralized apically administered virus. The results support the hypothesis that secretory IgA antibodies play a major role in preventing rotavirus diarrhea. Furthermore, the results show that the in vivo and in vitro methods described are useful tools for exploring the mechanisms of viral mucosal immunity.

* Corresponding author. Mailing address: Department of Virology, Smittskyddsinstitutet, 105 21 Stockholm, Sweden. Phone: 46 8 735 12 28. Fax: 46 8 470 56 13. E-mail: lensve{at}mbox.ki.se.




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