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. 1995 Apr;63(4):1611–1614. doi: 10.1128/iai.63.4.1611-1614.1995

Oral vaccination with an attenuated Salmonella typhimurium strain expressing Borrelia burgdorferi OspA prevents murine Lyme borreliosis.

M Dunne 1, B K al-Ramadi 1, S W Barthold 1, R A Flavell 1, E Fikrig 1
PMCID: PMC173199  PMID: 7890431

Abstract

Borrelia burgdorferi is the causative agent of Lyme disease. In the mouse model, protection is correlated with the development of antibodies to a major outer surface protein, OspA. In this study, we expressed OspA in an attenuated strain of Salmonella typhimurium and tested the efficacy of the transformed strain in protecting against disease. We show that mice inoculated by gavage developed high titers of anti-OspA antibodies and were protected against an intradermal challenge with the spirochete.

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Selected References

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  1. Aggarwal A., Kumar S., Jaffe R., Hone D., Gross M., Sadoff J. Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells. J Exp Med. 1990 Oct 1;172(4):1083–1090. doi: 10.1084/jem.172.4.1083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alpert B., Esin J., Sivak S. L., Wormser G. P. Incidence and prevalence of Lyme disease in a suburban Westchester County community. N Y State J Med. 1992 Jan;92(1):5–8. [PubMed] [Google Scholar]
  3. Bockenstedt L. K., Fikrig E., Barthold S. W., Kantor F. S., Flavell R. A. Inability of truncated recombinant Osp A proteins to elicit protective immunity to Borrelia burgdorferi in mice. J Immunol. 1993 Jul 15;151(2):900–906. [PubMed] [Google Scholar]
  4. Brett S. J., Rhodes J., Liew F. Y., Tite J. P. Comparison of antigen presentation of influenza A nucleoprotein expressed in attenuated AroA- Salmonella typhimurium with that of live virus. J Immunol. 1993 Apr 1;150(7):2869–2884. [PubMed] [Google Scholar]
  5. Chatfield S. N., Strahan K., Pickard D., Charles I. G., Hormaeche C. E., Dougan G. Evaluation of Salmonella typhimurium strains harbouring defined mutations in htrA and aroA in the murine salmonellosis model. Microb Pathog. 1992 Feb;12(2):145–151. doi: 10.1016/0882-4010(92)90117-7. [DOI] [PubMed] [Google Scholar]
  6. Clements J. D., Lyon F. L., Lowe K. L., Farrand A. L., el-Morshidy S. Oral immunization of mice with attenuated Salmonella enteritidis containing a recombinant plasmid which codes for production of the B subunit of heat-labile Escherichia coli enterotoxin. Infect Immun. 1986 Sep;53(3):685–692. doi: 10.1128/iai.53.3.685-692.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fikrig E., Barthold S. W., Kantor F. S., Flavell R. A. Long-term protection of mice from Lyme disease by vaccination with OspA. Infect Immun. 1992 Mar;60(3):773–777. doi: 10.1128/iai.60.3.773-777.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fikrig E., Barthold S. W., Kantor F. S., Flavell R. A. Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. Science. 1990 Oct 26;250(4980):553–556. doi: 10.1126/science.2237407. [DOI] [PubMed] [Google Scholar]
  9. Fikrig E., Barthold S. W., Kantor F. S., Flavell R. A. Protection of mice from Lyme borreliosis by oral vaccination with Escherichia coli expressing OspA. J Infect Dis. 1991 Dec;164(6):1224–1227. doi: 10.1093/infdis/164.6.1224. [DOI] [PubMed] [Google Scholar]
  10. Fikrig E., Telford S. R., 3rd, Barthold S. W., Kantor F. S., Spielman A., Flavell R. A. Elimination of Borrelia burgdorferi from vector ticks feeding on OspA-immunized mice. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5418–5421. doi: 10.1073/pnas.89.12.5418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Huycke M. M., D'Alessio D. D., Marx J. J. Prevalence of antibody to Borrelia burgdorferi by indirect fluorescent antibody assay, ELISA, and western immunoblot in healthy adults in Wisconsin and Arizona. J Infect Dis. 1992 Jun;165(6):1133–1137. doi: 10.1093/infdis/165.6.1133. [DOI] [PubMed] [Google Scholar]
  13. Killar L. M., Eisenstein T. K. Immunity to Salmonella typhimurium infection in C3H/HeJ and C3H/HeNCrlBR mice: studies with an aromatic-dependent live S. typhimurium strain as a vaccine. Infect Immun. 1985 Mar;47(3):605–612. doi: 10.1128/iai.47.3.605-612.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lastavica C. C. Deer, ticks, and Lyme disease. N Y State J Med. 1992 Jan;92(1):2–4. [PubMed] [Google Scholar]
  15. Levine M. M., Herrington D., Murphy J. R., Morris J. G., Losonsky G., Tall B., Lindberg A. A., Svenson S., Baqar S., Edwards M. F. Safety, infectivity, immunogenicity, and in vivo stability of two attenuated auxotrophic mutant strains of Salmonella typhi, 541Ty and 543Ty, as live oral vaccines in humans. J Clin Invest. 1987 Mar;79(3):888–902. doi: 10.1172/JCI112899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mukkur T. K., Walker K. H. Development and duration of protection against salmonellosis in mice and sheep immunised with live aromatic-dependent Salmonella typhimurium. Res Vet Sci. 1992 Mar;52(2):147–153. doi: 10.1016/0034-5288(92)90003-k. [DOI] [PubMed] [Google Scholar]
  17. Newton S. M., Jacob C. O., Stocker B. A. Immune response to cholera toxin epitope inserted in Salmonella flagellin. Science. 1989 Apr 7;244(4900):70–72. doi: 10.1126/science.2468182. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Poirier T. P., Kehoe M. A., Beachey E. H. Protective immunity evoked by oral administration of attenuated aroA Salmonella typhimurium expressing cloned streptococcal M protein. J Exp Med. 1988 Jul 1;168(1):25–32. doi: 10.1084/jem.168.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sadoff J. C., Ballou W. R., Baron L. S., Majarian W. R., Brey R. N., Hockmeyer W. T., Young J. F., Cryz S. J., Ou J., Lowell G. H. Oral Salmonella typhimurium vaccine expressing circumsporozoite protein protects against malaria. Science. 1988 Apr 15;240(4850):336–338. doi: 10.1126/science.3281260. [DOI] [PubMed] [Google Scholar]
  21. Schaible U. E., Kramer M. D., Eichmann K., Modolell M., Museteanu C., Simon M. M. Monoclonal antibodies specific for the outer surface protein A (OspA) of Borrelia burgdorferi prevent Lyme borreliosis in severe combined immunodeficiency (scid) mice. Proc Natl Acad Sci U S A. 1990 May;87(10):3768–3772. doi: 10.1073/pnas.87.10.3768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schödel F., Milich D. R., Will H. Hepatitis B virus nucleocapsid/pre-S2 fusion proteins expressed in attenuated Salmonella for oral vaccination. J Immunol. 1990 Dec 15;145(12):4317–4321. [PubMed] [Google Scholar]
  23. Sears J. E., Fikrig E., Nakagawa T. Y., Deponte K., Marcantonio N., Kantor F. S., Flavell R. A. Molecular mapping of Osp-A mediated immunity against Borrelia burgdorferi, the agent of Lyme disease. J Immunol. 1991 Sep 15;147(6):1995–2000. [PubMed] [Google Scholar]
  24. Tacket C. O., Hone D. M., Curtiss R., 3rd, Kelly S. M., Losonsky G., Guers L., Harris A. M., Edelman R., Levine M. M. Comparison of the safety and immunogenicity of delta aroC delta aroD and delta cya delta crp Salmonella typhi strains in adult volunteers. Infect Immun. 1992 Feb;60(2):536–541. doi: 10.1128/iai.60.2.536-541.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Telford S. R., 3rd, Fikrig E., Barthold S. W., Brunet L. R., Spielman A., Flavell R. A. Protection against antigenically variable Borrelia burgdorferi conferred by recombinant vaccines. J Exp Med. 1993 Aug 1;178(2):755–758. doi: 10.1084/jem.178.2.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tite J. P., Gao X. M., Hughes-Jenkins C. M., Lipscombe M., O'Callaghan D., Dougan G., Liew F. Y. Anti-viral immunity induced by recombinant nucleoprotein of influenza A virus. III. Delivery of recombinant nucleoprotein to the immune system using attenuated Salmonella typhimurium as a live carrier. Immunology. 1990 Aug;70(4):540–546. [PMC free article] [PubMed] [Google Scholar]
  27. al-Ramadi B. K., Chen Y. W., Meissler J. J., Jr, Eisenstein T. K. Immunosuppression induced by attenuated Salmonella. Reversal by IL-4. J Immunol. 1991 Sep 15;147(6):1954–1961. [PubMed] [Google Scholar]

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