Attenuated deltaguaBA Salmonella typhi vaccine strain CVD 915 as a live vector utilizing prokaryotic or eukaryotic expression systems to deliver foreign antigens and elicit immune responses.
Attenuated Salmonella typhi strain CVD 915, harboring a deletion in guaBA that interrupts the biosynthesis of guanine nucleotides, was evaluated as a live vector vaccine for delivering foreign antigens utilizing prokaryotic or eukaryotic expression systems. Plasmids pTETnir15 and pcDNA3tetC encoding fragment C (Frag C) of tetanus toxin under the control of prokaryotic or eukaryotic promoters, respectively, were introduced into CVD 915 and administered intranasally to mice. Purified pcDNA3tetC and Frag C were given intramuscularly. High titers of serum IgG1, IgG2a, and IgG2b antibodies against Frag C were elicited by CVD 915(pTETnir15) and CVD 915(pcDNA3tetC). These responses were significantly higher than those induced by pcDNA3tetC. Proliferative responses and IL-2 and IFN-gamma production were observed in splenocytes exposed to S. typhi antigens and Frag C. We conclude that CVD 915 is a highly efficient live vector to carry foreign genes under eukaryotic or prokaryotic control and elicit potent immune responses.
Department of Pediatrics, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA.
M F
MF
Pasetti
R J
RJ
Anderson
F R
FR
Noriega
M M
MM
Levine
M B
MB
Sztein
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D011994:Recombinant Proteins / Q000276:immunology; D012485:Salmonella typhi / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D014613:Vaccines, Attenuated / Q000008:administration & dosage*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D016207:Cytokines; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated