Efficacy, heat stability and safety of intranasally administered Bacillus subtilis spore or vegetative cell vaccines expressing tetanus toxin fragment C.
Bacillus subtilis strains expressing tetanus toxin fragment C (TTFC) were tested as vaccine candidates against tetanus in adult mice. Mice received three intranasal (IN) exposures to 10(9) spores or 10(8) vegetative cells of B. subtilis expressing recombinant TTFC. Immunized mice generated protective systemic and mucosal antibodies and survived challenge with 2× LD(100) of tetanus toxin. Isotype analysis of serum antibody indicated a balanced Th1/Th2 response. Lyophilized vaccines stored at 45° C for ≥ 12 months, remained effective. Immunized conventional and SCID mice remained well, and no histological changes in brain or respiratory tract were detected. Lyophilized/reconstituted B. subtilis tetanus vaccines administered IN to mice appear safe, heat-stable, and protective against lethal tetanus challenge.
Lee
Sangun
S
Division of Infectious Diseases, Tufts University, Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA.
Belitsky
Boris R
BR
Brown
David W
DW
Brinker
James P
JP
Kerstein
Kathryn O
KO
Herrmann
John E
JE
Keusch
Gerald T
GT
Sonenshein
Abraham L
AL
Tzipori
Saul
S
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001412:Bacillus subtilis / Q000276:immunology; D001483:Base Sequence; D005260:Female; D005612:Freeze Drying; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D013742:Tetanus / Q000276:immunology / Q000517:prevention & control*; D013744:Tetanus Toxin / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*
D000907:Antibodies, Bacterial; D010446:Peptide Fragments; D013744:Tetanus Toxin; D013745:Tetanus Toxoid; C040635:tetanus toxin fragment C