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Journal of Virology, January 2002, p. 560-568, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.560-568.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

CD4 T Cells Are the Only Lymphocytes Needed To Protect Mice against Rotavirus Shedding after Intranasal Immunization with a Chimeric VP6 Protein and the Adjuvant LT(R192G)

Monica M. McNeal,1 John L. VanCott,1 Anthony H. C. Choi,1 Matili Basu,1 Jason A. Flint,1 Susan C. Stone,1 John D. Clements,2 and Richard L. Ward1*

Division of Infectious Diseases, Children’s Hospital Medical Center, Cincinnati, Ohio 45229,1 Department of Microbiology and Immunology, Tulane University Medical Center, New Orleans, Louisiana 701122

Received 15 June 2001/ Accepted 11 October 2001

Intranasal immunization of mice with a chimeric VP6 protein and the mucosal adjuvant Escherichia coli heat labile toxin LT(R192G) induces nearly complete protection against murine rotavirus (strain EDIM [epizootic diarrhea of infant mice virus]) shedding for at least 1 year. The aim of this study was to identify the protective lymphocytes elicited by this new vaccine candidate. Immunization of mouse strains lacking one or more lymphocyte populations revealed that protection was dependent on {alpha}ß T cells but mice lacking {gamma}{delta} T cells and B cells remained fully protected. Furthermore, depletion of CD8 T cells in immunized B-cell-deficient mice before challenge resulted in no loss of protection, while depletion of CD4 T cells caused complete loss of protection. Therefore, {alpha}ß CD4 T cells appeared to be the only lymphocytes required for protection. As confirmation, purified splenic T cells from immunized mice were intraperitoneally injected into Rag-2 mice chronically infected with EDIM. Transfer of 2 x 106 CD8 T cells had no effect on shedding, while transfer of 2 x 105 CD4 T cells fully resolved shedding in 7 days. Interestingly, transfer of naive splenic CD4 T cells also resolved shedding but more time and cells were required. Together, these results establish CD4 T cells as effectors of protection against rotavirus after intranasal immunization of mice with VP6 and LT(R192G).

* Corresponding author. Mailing address: Division of Infectious Diseases, Children’s Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229. Phone: (513) 636-7628. Fax: (513) 636-7682. E-mail: wardd0{at}chmcc.org.

Journal of Virology, January 2002, p. 560-568, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.560-568.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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