Bacterial Spores As Vaccine Vehicles

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2003 Apr 22

PMID 12704155

Citations 64

Authors

Le H Duc

Huynh A Hong

Neil Fairweather

Ezio Ricca

Simon M Cutting

Affiliations

Soon will be listed here.

Abstract

For the first time, bacterial spores have been evaluated as vaccine vehicles. Bacillus subtilis spores displaying the tetanus toxin fragment C (TTFC) antigen were used for oral and intranasal immunization and were shown to generate mucosal and systemic responses in a murine model. TTFC-specific immunoglobulin G titers in serum (determined by enzyme-linked immunosorbent assay) reached significant levels 33 days after oral dosing, while responses against the spore coat proteins were relatively low. Tetanus antitoxin levels were sufficient to protect against an otherwise lethal challenge of tetanus toxin (20 50% lethal doses). The robustness and long-term storage properties of bacterial spores, coupled with simplified genetic manipulation and cost-effective manufacturing, make them particularly attractive vehicles for oral and intranasal vaccination.

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References

Hoa T, Duc L, Isticato R, Baccigalupi L, Ricca E, Van P . Fate and dissemination of Bacillus subtilis spores in a murine model. Appl Environ Microbiol. 2001; 67(9):3819-23. PMC: 93096. DOI: 10.1128/AEM.67.9.3819-3823.2001. View

Driks A . Bacillus subtilis spore coat. Microbiol Mol Biol Rev. 1999; 63(1):1-20. PMC: 98955. DOI: 10.1128/MMBR.63.1.1-20.1999. View

Casula G, Cutting S . Bacillus probiotics: spore germination in the gastrointestinal tract. Appl Environ Microbiol. 2002; 68(5):2344-52. PMC: 127533. DOI: 10.1128/AEM.68.5.2344-2352.2002. View

Piggot P, Coote J . Genetic aspects of bacterial endospore formation. Bacteriol Rev. 1976; 40(4):908-62. PMC: 413989. DOI: 10.1128/br.40.4.908-962.1976. View

Challacombe S . Salivary antibodies and systemic tolerance in mice after oral immunization with bacterial antigens. Ann N Y Acad Sci. 1983; 409:177-93. DOI: 10.1111/j.1749-6632.1983.tb26868.x. View

Youngman P, Perkins J, Losick R . Construction of a cloning site near one end of Tn917 into which foreign DNA may be inserted without affecting transposition in Bacillus subtilis or expression of the transposon-borne erm gene. Plasmid. 1984; 12(1):1-9. DOI: 10.1016/0147-619x(84)90061-1. View

Romanos M, Makoff A, Fairweather N, Beesley K, Slater D, Rayment F . Expression of tetanus toxin fragment C in yeast: gene synthesis is required to eliminate fortuitous polyadenylation sites in AT-rich DNA. Nucleic Acids Res. 1991; 19(7):1461-7. PMC: 333902. DOI: 10.1093/nar/19.7.1461. View

Chatfield S, Charles I, Makoff A, Oxer M, Dougan G, Pickard D . Use of the nirB promoter to direct the stable expression of heterologous antigens in Salmonella oral vaccine strains: development of a single-dose oral tetanus vaccine. Biotechnology (N Y). 1992; 10(8):888-92. DOI: 10.1038/nbt0892-888. View

Errington J . Bacillus subtilis sporulation: regulation of gene expression and control of morphogenesis. Microbiol Rev. 1993; 57(1):1-33. PMC: 372899. DOI: 10.1128/mr.57.1.1-33.1993. View

10.

Mazza P . The use of Bacillus subtilis as an antidiarrhoeal microorganism. Boll Chim Farm. 1994; 133(1):3-18. View

11.

Li Y, Foran P, Fairweather N, de Paiva A, Weller U, Dougan G . A single mutation in the recombinant light chain of tetanus toxin abolishes its proteolytic activity and removes the toxicity seen after reconstitution with native heavy chain. Biochemistry. 1994; 33(22):7014-20. DOI: 10.1021/bi00188a034. View

12.

Douce G, Turcotte C, Cropley I, Roberts M, Pizza M, Domenghini M . Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants. Proc Natl Acad Sci U S A. 1995; 92(5):1644-8. PMC: 42576. DOI: 10.1073/pnas.92.5.1644. View

13.

Harry E, Pogliano K, Losick R . Use of immunofluorescence to visualize cell-specific gene expression during sporulation in Bacillus subtilis. J Bacteriol. 1995; 177(12):3386-93. PMC: 177040. DOI: 10.1128/jb.177.12.3386-3393.1995. View

14.

Figueiredo D, Turcotte C, Frankel G, Li Y, Dolly O, Wilkin G . Characterization of recombinant tetanus toxin derivatives suitable for vaccine development. Infect Immun. 1995; 63(8):3218-21. PMC: 173441. DOI: 10.1128/iai.63.8.3218-3221.1995. View

15.

Robinson K, Chamberlain L, Schofield K, Wells J, Le Page R . Oral vaccination of mice against tetanus with recombinant Lactococcus lactis. Nat Biotechnol. 1997; 15(7):653-7. DOI: 10.1038/nbt0797-653. View

16.

Labruyere E, Mock M . Germination of Bacillus anthracis spores within alveolar macrophages. Mol Microbiol. 1999; 31(1):9-17. DOI: 10.1046/j.1365-2958.1999.01137.x. View

17.

Isticato R, Cangiano G, Tran H, CIABATTINI A, Medaglini D, Oggioni M . Surface display of recombinant proteins on Bacillus subtilis spores. J Bacteriol. 2001; 183(21):6294-301. PMC: 100119. DOI: 10.1128/JB.183.21.6294-6301.2001. View