Abstract
A Salmonella typhimurium aroA mutant has been used as a live carrier to immunize mice against tetanus. Plasmid pTETtac4, which expresses a 50-kilodalton fragment of tetanus toxin (fragment C) under the control of the tac promoter, was introduced into SL3261 aroA. When used as a live vaccine and administered orally or intravenously, this strain was able to induce protective immunity in mice against a lethal tetanus toxin challenge. When plasmid pTETtac2, which contains the lacI gene, was used, no immunity was obtained, indicating that the expression of fragment C was repressed in vivo. We believe that this is the first example of a successful oral vaccination that uses an attenuated bacterial carrier to deliver a protective antigen derived from tetanus toxin.
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- Amann E., Brosius J., Ptashne M. Vectors bearing a hybrid trp-lac promoter useful for regulated expression of cloned genes in Escherichia coli. Gene. 1983 Nov;25(2-3):167–178. doi: 10.1016/0378-1119(83)90222-6. [DOI] [PubMed] [Google Scholar]
- Angus P. W., Mihaly G. W., Morgan D. J., Smallwood R. A. Oxygen dependence of omeprazole clearance and sulfone and sulfide metabolite formation in the isolated perfused rat liver. J Pharmacol Exp Ther. 1989 Sep;250(3):1043–1047. [PubMed] [Google Scholar]
- Bullas L. R., Ryu J. I. Salmonella typhimurium LT2 strains which are r- m+ for all three chromosomally located systems of DNA restriction and modification. J Bacteriol. 1983 Oct;156(1):471–474. doi: 10.1128/jb.156.1.471-474.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dorman C. J., Chatfield S., Higgins C. F., Hayward C., Dougan G. Characterization of porin and ompR mutants of a virulent strain of Salmonella typhimurium: ompR mutants are attenuated in vivo. Infect Immun. 1989 Jul;57(7):2136–2140. doi: 10.1128/iai.57.7.2136-2140.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dougan G., Chatfield S., Pickard D., Bester J., O'Callaghan D., Maskell D. Construction and characterization of vaccine strains of Salmonella harboring mutations in two different aro genes. J Infect Dis. 1988 Dec;158(6):1329–1335. doi: 10.1093/infdis/158.6.1329. [DOI] [PubMed] [Google Scholar]
- Dougan G., Maskell D., Pickard D., Hormaeche C. Isolation of stable aroA mutants of Salmonella typhi Ty2: properties and preliminary characterisation in mice. Mol Gen Genet. 1987 May;207(2-3):402–405. doi: 10.1007/BF00331607. [DOI] [PubMed] [Google Scholar]
- Eisel U., Jarausch W., Goretzki K., Henschen A., Engels J., Weller U., Hudel M., Habermann E., Niemann H. Tetanus toxin: primary structure, expression in E. coli, and homology with botulinum toxins. EMBO J. 1986 Oct;5(10):2495–2502. doi: 10.1002/j.1460-2075.1986.tb04527.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fairweather N. F., Lyness V. A., Maskell D. J. Immunization of mice against tetanus with fragments of tetanus toxin synthesized in Escherichia coli. Infect Immun. 1987 Nov;55(11):2541–2545. doi: 10.1128/iai.55.11.2541-2545.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fairweather N. F., Lyness V. A., Pickard D. J., Allen G., Thomson R. O. Cloning, nucleotide sequencing, and expression of tetanus toxin fragment C in Escherichia coli. J Bacteriol. 1986 Jan;165(1):21–27. doi: 10.1128/jb.165.1.21-27.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fairweather N. F., Lyness V. A. The complete nucleotide sequence of tetanus toxin. Nucleic Acids Res. 1986 Oct 10;14(19):7809–7812. doi: 10.1093/nar/14.19.7809. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farzad Z., James K. Isotype responses of mice to tetanus-toxoid preparations. J Med Microbiol. 1986 Nov;22(3):189–193. doi: 10.1099/00222615-22-3-189. [DOI] [PubMed] [Google Scholar]
- Germanier R., Füer E. Isolation and characterization of Gal E mutant Ty 21a of Salmonella typhi: a candidate strain for a live, oral typhoid vaccine. J Infect Dis. 1975 May;131(5):553–558. doi: 10.1093/infdis/131.5.553. [DOI] [PubMed] [Google Scholar]
- Helting T. B., Nau H. H. Analysis of the immune response to papain digestion products of tetanus toxin. Acta Pathol Microbiol Immunol Scand C. 1984 Feb;92(1):59–63. doi: 10.1111/j.1699-0463.1984.tb00052.x. [DOI] [PubMed] [Google Scholar]
- Helting T. B., Zwisler O. Structure of tetanus toxin. I. Breakdown of the toxin molecule and discrimination between polypeptide fragments. J Biol Chem. 1977 Jan 10;252(1):187–193. [PubMed] [Google Scholar]
- Helting T. B., Zwisler O., Wiegandt H. Structure of tetanus toxin. II. Toxin binding to ganglioside. J Biol Chem. 1977 Jan 10;252(1):194–198. [PubMed] [Google Scholar]
- Hoiseth S. K., Stocker B. A. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature. 1981 May 21;291(5812):238–239. doi: 10.1038/291238a0. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Maskell D. J., Sweeney K. J., O'Callaghan D., Hormaeche C. E., Liew F. Y., Dougan G. Salmonella typhimurium aroA mutants as carriers of the Escherichia coli heat-labile enterotoxin B subunit to the murine secretory and systemic immune systems. Microb Pathog. 1987 Mar;2(3):211–221. doi: 10.1016/0882-4010(87)90022-2. [DOI] [PubMed] [Google Scholar]
- Miller I., Maskell D., Hormaeche C., Johnson K., Pickard D., Dougan G. Isolation of orally attenuated Salmonella typhimurium following TnphoA mutagenesis. Infect Immun. 1989 Sep;57(9):2758–2763. doi: 10.1128/iai.57.9.2758-2763.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Callaghan D., Maskell D., Liew F. Y., Easmon C. S., Dougan G. Characterization of aromatic- and purine-dependent Salmonella typhimurium: attention, persistence, and ability to induce protective immunity in BALB/c mice. Infect Immun. 1988 Feb;56(2):419–423. doi: 10.1128/iai.56.2.419-423.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmieger H. Phage P22-mutants with increased or decreased transduction abilities. Mol Gen Genet. 1972;119(1):75–88. doi: 10.1007/BF00270447. [DOI] [PubMed] [Google Scholar]
- Sheppard A. J., Cussell D., Hughes M. Production and characterization of monoclonal antibodies to tetanus toxin. Infect Immun. 1984 Feb;43(2):710–714. doi: 10.1128/iai.43.2.710-714.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stanfield J. P., Galazka A. Neonatal tetanus in the world today. Bull World Health Organ. 1984;62(4):647–669. [PMC free article] [PubMed] [Google Scholar]
- Veronesi R., Bizzini B., Focaccia R., Coscina A. L., Mazza C. C., Focaccia M. T., Carraro F., Honningman M. N. Naturally acquired antibodies to tetanus toxin in humans and animals from the galápagos islands. J Infect Dis. 1983 Feb;147(2):308–311. doi: 10.1093/infdis/147.2.308. [DOI] [PubMed] [Google Scholar]
- van Heyningen S. Binding of ganglioside by the chains of tetanus toxin. FEBS Lett. 1976 Sep 15;68(1):5–7. doi: 10.1016/0014-5793(76)80391-2. [DOI] [PubMed] [Google Scholar]

