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Infection and Immunity, November 1999, p. 5799-5805, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Evaluation of a Truncated Recombinant Flagellin Subunit Vaccine against Campylobacter jejuni

Lanfong H. Lee,1 Edward Burg III,1 Shahida Baqar,1 A. L. Bourgeois,1 Don H. Burr,1,2 Cheryl P. Ewing,1 Trevor J. Trust,3 and Patricia Guerry1,*

Enteric Diseases Program, Naval Medical Research Center, Bethesda, Maryland 20889-56071; Food and Drug Administration, Beltsville, Maryland 207082; and Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia V8W 3P6, Canada3

Received 5 May 1999/Returned for modification 7 July 1999/Accepted 16 August 1999

A recombinant protein comprising the maltose-binding protein (MBP) of Escherichia coli fused to amino acids 5 to 337 of the FlaA flagellin of Campylobacter coli VC167 was evaluated for immunogenicity and protective efficacy against challenge by a heterologous strain of campylobacter, Campylobacter jejuni 81-176, in two murine models. The sequence of the flaA gene of strain 81-176 revealed a predicted protein which was 98.1% similar to that of VC167 FlaA over the region expressed in the fusion protein. Mice were immunized intranasally with two doses of 3 to 50 µg of MBP-FlaA, given 8 days apart, with or without 5 µg of the mutant E. coli heat-labile enterotoxin (LTR192G) as a mucosal adjuvant. The full range of MBP-FlaA doses were effective in eliciting antigen-specific serum immunoglobulin G (IgG) responses, and these responses were enhanced by adjuvant use, except in the highest dosing group. Stimulation of FlaA-specific intestinal secretory IgA (sIgA) responses required immunization with higher doses of MBP-FlaA (>= 25 µg) or coadministration of lower doses with the adjuvant. When vaccinated mice were challenged intranasally 26 days after immunization, the best protection was seen in animals given 50 µg of MBP-FlaA plus LTR192G. The protective efficacies of this dose against disease symptoms and intestinal colonization were 81.1 and 84%, respectively. When mice which had been immunized with 50 µg of MBP-FlaA plus LTR192G intranasally were challenged orally with 8 × 1010, 8 × 109, or 8 × 108 cells of strain 81-176, the protective efficacies against intestinal colonization at 7 days postinfection were 71.4, 71.4, and 100%, respectively.

* Corresponding author. Mailing address: Naval Medical Research Center, National Naval Medical Center, 8901 Wisconsin Ave., Bethesda, MD 20889-5607. Phone: (301) 319-7662. Fax: (301) 319-7679. E-mail: guerryp{at}nmripo.nmri.nnmc.navy.mil.

Infection and Immunity, November 1999, p. 5799-5805, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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