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.
Pasetti
M F
MF
Department of Pediatrics, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA.
Anderson
R J
RJ
Noriega
F R
FR
Levine
M M
MM
Sztein
M B
MB
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