Attenuated Salmonella as live oral vaccines against typhoid fever and as live vectors.
Attenuated Salmonella typhi vaccine strain CVD 908, which harbors deletion mutations in aroC and aroD, has been shown to be well-tolerated and highly immunogenic, eliciting impressive serum antibody, mucosal IgA and cell-mediated immune responses. A further derivative prepared by introducing a deletion in htrA (which encodes a heat-shock protein that also has activity as a serine protease in CVD 908 (Chatfield et al., unpublished data) resulted in CVD 908-htrA. In phase 1 clinical trials, CVD 908-htrA appears very attractive as a live oral vaccine candidate. Both CVD 908 and CVD 908-htrA are useful as live vector vaccines to deliver foreign antigens to the immune system. Conditions that enhance the expression and immunogenicity of foreign antigens carried by CVD 908 and CVD 908-htrA are being investigated.
Levine
M M
MM
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore 21201, USA.
Galen
J
J
Barry
E
E
Noriega
F
F
Chatfield
S
S
Sztein
M
M
Dougan
G
G
Tacket
C
C
D000284:Administration, Oral; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D005798:Genes, Bacterial; D006360:Heat-Shock Proteins; D006801:Humans; D007111:Immunity, Cellular; D016296:Mutagenesis; D033903:Periplasmic Proteins; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology*; D017384:Sequence Deletion; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology; D014435:Typhoid Fever / Q000276:immunology* / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000008:administration & dosage
D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D006360:Heat-Shock Proteins; D033903:Periplasmic Proteins; D014613:Vaccines, Attenuated; C061682:DegP protease; D012697:Serine Endopeptidases