Safety and immune responses to attenuated Salmonella enterica serovar typhi oral live vector vaccines expressing tetanus toxin fragment C.
Attenuated Salmonella enterica serovar Typhi vaccine strain CVD 908-htrA was used as a vector to deliver fragment C of tetanus toxin as a single-dose oral tetanus vaccine candidate to elicit protective levels of serum tetanus antitoxin. Twenty-one healthy adult volunteers received doses of 1.6 x 10(7) to 8.2 x 10(9) CFU of one of two strains, CVD 908-htrA(pTETnir15) or CVD 908-htrA(pTETlpp), which contained plasmid-encoded fragment C, with sodium bicarbonate, and the safety and immune responses to serovar Typhi antigens and tetanus toxin were assessed. No volunteer had fever or positive blood cultures after vaccination, although diarrhea occurred in 3 volunteers and vomiting in 2 volunteers within 3 weeks after vaccination. Most volunteers excreted the vaccine strain in the first 72 h after vaccination. Three of nine volunteers who received 10(8) CFU or higher doses of the CVD 908-htrA(pTETlpp) construct developed rises in serum antitoxin antibodies. The serum and cellular immune responses to serovar Typhi antigens were less frequent than those previously observed in volunteers who ingested the parent strain CVD 908-htrA. This study demonstrates that fragment C of tetanus toxin delivered orally to volunteers in an S. Typhi vector can elicit protective levels of serum antitoxin.
Tacket
C O
CO
Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, Maryland 21201, USA. ctacket@medicine.umaryland.edu
Galen
J
J
Sztein
M B
MB
Losonsky
G
G
Wyant
T L
TL
Nataro
J
J
Wasserman
S S
SS
Edelman
R
R
Chatfield
S
S
Dougan
G
G
Levine
M M
MM
D000293:Adolescent; D000328:Adult; D000818:Animals; D000917:Antibody Formation; D003257:Consumer Product Safety; D004337:Drug Carriers / Q000627:therapeutic use; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000627:therapeutic use; D022562:Salmonella Vaccines / Q000276:immunology* / Q000627:therapeutic use; D012485:Salmonella typhi / Q000276:immunology*; D013744:Tetanus Toxin / Q000008:administration & dosage* / Q000627:therapeutic use; D014613:Vaccines, Attenuated / Q000276:immunology* / Q000627:therapeutic use
D004337:Drug Carriers; D004338:Drug Combinations; D010446:Peptide Fragments; D022562:Salmonella Vaccines; D013744:Tetanus Toxin; D014613:Vaccines, Attenuated; C040635:tetanus toxin fragment C