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Infection and Immunity, May 2004, p. 2753-2761, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2753-2761.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mucosal and Cellular Immune Responses Elicited by Recombinant Lactococcus lactis Strains Expressing Tetanus Toxin Fragment C

K. Robinson,* L. M. Chamberlain, M. C. Lopez,{dagger} C. M. Rush,{ddagger} H. Marcotte,§ R. W. F. Le Page, and J. M. Wells||

The Cortecs Centre for Vaccine Discovery, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom

Received 21 November 2003/ Returned for modification 23 December 2003/ Accepted 21 January 2004

The mucosal and cellular responses of mice were studied, following mucosal-route administration of recombinant Lactococcus lactis expressing tetanus toxin fragment C (TTFC), which is a known immunogen protective against tetanus. A TTFC-specific T-cell response with a mixed profile of T-helper (Th) subset-associated cytokines was elicited in the intestine, with a Th2 bias characteristic of a mucosal response. These results correlated with the humoral response, where equivalent titers of anti-TTFC immunoglobulin G1 (IgG1) and IgG2a in serum were accompanied by an elevated IgA-specific response at more than one mucosal site. The route of vaccination had an important role in determining the immune response phenotype, as evidenced by the fact that an IgG1-biased subclass profile was obtained when lactococci were administered parenterally. Stimulation of splenic or mesenteric lymph node cells with lactococci resulted in their proliferation and the secretion of gamma interferon via antigen-specific and innate immune mechanisms. The data therefore provide further evidence of the potential of recombinant lactococcal vaccines for inducing systemic and mucosal immune responses.

* Corresponding author. Mailing address: Institute of Infection, Immunity and Inflammation, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, United Kingdom. Phone: 44 (0) 1159 249924, ext. 42457. Fax: 44 (0) 115 970 9923. E-mail: Karen.robinson{at}nottingham.ac.uk.

Editor: J. N. Weiser

{dagger} Present address: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208-3479.

{ddagger} Present address: Division of Immunology, Infection and Inflammation, Western Infirmary, University of Glasgow, Glasgow G11 6NT, United Kingdom.

§ Present address: Center for Oral Biology at NOVUM, Karolinska Institute, S-141 04 Huddinge, Sweden.

|| Present address: Institute of Food Research, Food Safety Science, Norwich Research Park, Colney, NR4 7UA Norwich, United Kingdom.

Infection and Immunity, May 2004, p. 2753-2761, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2753-2761.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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