Evaluation of a truncated recombinant flagellin subunit vaccine against Campylobacter jejuni.
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 microgram of MBP-FlaA, given 8 days apart, with or without 5 microgram of the mutant E. coli heat-labile enterotoxin (LT(R192G)) 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 microgram) 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 microgram of MBP-FlaA plus LT(R192G). 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 microgram of MBP-FlaA plus LT(R192G) intranasally were challenged orally with 8 x 10(10), 8 x 10(9), or 8 x 10(8) cells of strain 81-176, the protective efficacies against intestinal colonization at 7 days postinfection were 71.4, 71.4, and 100%, respectively.
Lee
L H
LH
Enteric Diseases Program, Naval Medical Research Center, Bethesda, Maryland 20889-5607, USA.
Burg
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E
Baqar
S
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Bourgeois
A L
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Burr
D H
DH
Ewing
C P
CP
Trust
T J
TJ
Guerry
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P
D000595:Amino Acid Sequence; D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D016123:Campylobacter jejuni / Q000276:immunology*; D005408:Flagellin / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D001428:Bacterial Vaccines; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D005408:Flagellin; C067138:flaA protein, bacteria