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Journal of Virology, January 2004, p. 947-957, Vol. 78, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.2.947-957.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Secretory Immunoglobulin A Antibodies against the {sigma}1 Outer Capsid Protein of Reovirus Type 1 Lang Prevent Infection of Mouse Peyer's Patches{dagger}

Amy B. Hutchings,1,2,{ddagger} Anna Helander,1,2,§ Katherine J. Silvey,1,2,¶ Kartik Chandran,3,|| William T. Lucas,3,# Max L. Nibert,3 and Marian R. Neutra1,2*

GI Cell Biology Laboratory, Children's Hospital,1 Departments of Pediatrics,2 Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 021153

Received 19 May 2003/ Accepted 2 October 2003

Reovirus type 1 Lang (T1L) adheres to M cells in the follicle-associated epithelium of mouse intestine and exploits the transport activity of M cells to enter and infect the Peyer's patch mucosa. Adult mice that have previously cleared a reovirus T1L infection have virus-specific immunoglobulin G (IgG) in serum and IgA in secretions and are protected against reinfection. Our aim in this study was to determine whether secretory IgA is sufficient for protection of Peyer's patches against oral reovirus challenge and, if so, against which reovirus antigen(s) the IgA may be directed. Monoclonal antibodies (MAbs) of the IgA isotype, directed against the {sigma}1 protein of reovirus T1L, the viral adhesin, were produced and tested along with other, existing IgA and IgG MAbs against reovirus T1L outer capsid proteins. Anti-{sigma}1 IgA and IgG MAbs neutralized reovirus T1L in L cell plaque reduction assays and inhibited T1L adherence to L cells and Caco-2BBe intestinal epithelial cells in vitro, but MAbs against other proteins did not. Passive oral administration of anti-{sigma}1 IgA and IgG MAbs prevented Peyer's patch infection in adult mice, but other MAbs did not. When anti-{sigma}1 IgA and IgG MAbs were produced in mice from hybridoma backpack tumors, however, the IgA prevented Peyer's patch infection, but the IgG did not. The results provide evidence that neutralizing IgA antibodies specific for the {sigma}1 protein are protective in vitro and in vivo and that the presence of these antibodies in intestinal secretions is sufficient for protection against entry of reovirus T1L into Peyer's patches.

* Corresponding author. Mailing address: GI Cell Biology Laboratory, Enders 1220, Children's Hospital, 300 Longwood Ave., Boston, MA 02115. Phone: (617) 355-6229. Fax: (617) 730-0498. E-mail: marian.neutra{at}tch.harvard.edu.

{dagger} This study is dedicated to the memory of our friend and colleague Bernard N. Fields.

{ddagger} Present address: UCB Research, Inc., Cambridge, MA 02139.

§ Present address: Dept. of Histology and Microbiology, University of Padua, Padua, 35121 Italy.

Present address: Aphton Corp., Woodland, CA 95776.

|| Present address: Dept. of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston, MA 02115.

# Present address: AppTec Laboratory Services, Camden, NJ 08104.

Journal of Virology, January 2004, p. 947-957, Vol. 78, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.2.947-957.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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