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Journal of Virology, August 2002, p. 8110-8117, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8110-8117.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Heterologous Protection Induced by the Inner Capsid Proteins of Rotavirus Requires Transcytosis of Mucosal Immunoglobulins

U892 INRA, Domaine de Vilvert, 78352 Jouy-en-Josas, France,¹ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305,² Palo Alto V.A. Health Care System, Palo Alto, California 94304,³ Section of Pediatric Infectious Diseases, University of Chicago Children's Hospital, Chicago, Illinois 60637⁴

Received 29 January 2002/ Accepted 17 May 2002

Protective immunization against rotavirus (RV) can be achieved with heterologous RV, i.e., virus isolated from another species, and with heterologous inner core VP2 and VP6 proteins assembled as virus-like particles (VLP). Although the antigenically conserved VP6 protein does not induce in vitro-neutralizing antibodies, it may, however, elicit immunoglobulins (Ig) involved in heterologous protection, as some IgA against VP6 prevent RV infection in a backpack mouse model. The protective role of Ig directed to the RV inner core proteins VP2 and VP6 was investigated in J-chain-deficient mice (J chain^-/-), which have a defect in the polymeric Ig receptor (pIgR)-mediated transcytosis of IgA and IgM. J chain^-/- mice and wild-type (WT) mice were intranasally vaccinated with bovine RV-derived VLP2/6 and then challenged with highly infectious murine ECw RV. Whereas WT mice were totally protected, immunized J chain^-/- mice shed RV for several days. In addition, naïve J chain^-/- mice exhibited a 2-day delay in clearing RV compared with WT mice. The immunized J chain^-/- mice displayed unaltered VLP2/6-specific B-cell numbers in spleen and in mesenteric nodes and similar levels of serum anti-VLP2/6 Ig, confirming that the adaptive B-cell response is preserved in J chain^-/- mice. These results indicate that J-chain-mediated transcytosis of Ig participates in the clearance of RV and that epithelial pIgR-mediated transport of Ig is involved in the heterologous protection induced by VLP2/6.

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