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Infection and Immunity, May 2003, p. 2810-2818, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2810-2818.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Bacterial Spores as Vaccine Vehicles

Le H. Duc,1 Huynh A. Hong,1 Neil Fairweather,2 Ezio Ricca,3 and Simon M. Cutting1*

School of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX,1 Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AY, United Kingdom,2 Department of General and Environmental Physiology, Section of Microbiology, University Federico II, 80134 Naples, Italy3

Received 5 November 2002/ Returned for modification 24 January 2003/ Accepted 12 February 2003

For the first time, bacterial spores have been evaluated as vaccine vehicles. Bacillus subtilis spores displaying the tetanus toxin fragment C (TTFC) antigen were used for oral and intranasal immunization and were shown to generate mucosal and systemic responses in a murine model. TTFC-specific immunoglobulin G titers in serum (determined by enzyme-linked immunosorbent assay) reached significant levels 33 days after oral dosing, while responses against the spore coat proteins were relatively low. Tetanus antitoxin levels were sufficient to protect against an otherwise lethal challenge of tetanus toxin (20 50% lethal doses). The robustness and long-term storage properties of bacterial spores, coupled with simplified genetic manipulation and cost-effective manufacturing, make them particularly attractive vehicles for oral and intranasal vaccination.

* Corresponding author. Mailing address: School of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, United Kingdom. Phone: 44-(0)1784-443760. Fax: 44-(0)1784-434326. E-mail: s.cutting{at}rhul.ac.uk.

Editor: J. D. Clements

Infection and Immunity, May 2003, p. 2810-2818, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2810-2818.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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