Stable Recombinant Avirulent Salmonella Vaccine Strains

  • Roy CurtissIII
  • Sandra M. Kelly
  • Paul A. Gulig
  • Koji Nakayama


All infectious disease agents have specific mechanisms to colonize , invade , and overcome the host. By use of gene cloning and genetic and biochemical techniques , it is possible to elucidate these mechanisms in biochemical terms as well as to understand the biology by which pathogens accomplish these feats . Once these mechanisms are understood, the information can be used to design novel strategies to immunize the host to prevent infection and disease by the pathogen. Since most pathogens colonize on and invade through a mucosal surface, it is appropriate to develop an immunization strategy that elicits a mucosal immune response as well as production of serum IgG and a cellular immune response.


Vaccine Strain Streptococcus Mutans Oral Immunization Diaminopimelic Acid Semialdehyde Dehydrogenase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bacon GA, Burrows TW, Yates M (1950) The effects of biochemical mutation on the virulence of Bacterium typhosum: the virulence of mutants. Brit J Exp Pathol 32:714–724Google Scholar
  2. Bacon GA, Burrows TW, Yates M (1951) The effects of biochemical mutation on the virulence of Bacterium typhosum: the loss of virulence of certain mutants. Brit J Exp Pathol 32:85–96Google Scholar
  3. Barrow PA, Simpson JM, Lovell MA, Binns MM (1987) Contribution of Salmonella gallinarum large plasmid toward virulence in fowl typhoid. Infect Immun 55:388–392PubMedGoogle Scholar
  4. Bienenstock J, McDermott M, Befus D, O’Neil LM (1978) A common mucosal immunologic system involving the bronchus, breast, and bowel. Adv Exp Med Biol 107:53–59PubMedCrossRefGoogle Scholar
  5. Brandtzaeg P (1988) Overview of the Mucosal Immune System. Curr Top Microbiol Immun In press.Google Scholar
  6. Cardineau GA, Curtiss R III (1987) Nucleotide sequence of the asd gene of Streptococcus mutans: identification of the promoter region and evidence for attenuator like sequences preceding the structural gene. J Biol Chem 262:3344–3353PubMedGoogle Scholar
  7. Carter PB, Collins FM (1974) The route of enteric infection in normal mice. J Exp Med 139:1189–1203PubMedCrossRefGoogle Scholar
  8. Cebra JJ, Gearhart PJ, Kamat R, Robertson SM, Tseng J (1976) Origin and differentiation of lymphocytes involved in the secretory IgA response. Cold Spring Harbor Symp Quant Biol 41:201–221CrossRefGoogle Scholar
  9. Curtiss R III (1985) Genetic analysis of Streptococcus mutans virulence. Curr Top Microbiol Immun 118:253–277CrossRefGoogle Scholar
  10. Curtiss R III (1986) Genetic analysis of Streptococcus mutans virulence and prospects for an anticaries vaccine. J Dent Res 65:1034–1045PubMedCrossRefGoogle Scholar
  11. Curtiss R III, Goldschmidt R, Barrett J, Thoren-Gordon M, Salzberg DJ, Murchison HH, Michalek SM (1987a) Genetic analysis of surface proteins essential for virulence of Streptcoccus sobrinus, pp. 212–216 In: Streptoccal Genetics Ferretti JJ, Curtiss R III (eds) American Society for Microbiology, Washington DCGoogle Scholar
  12. Curtiss R III, Goldschmidt R, Kelly SM, Lyons M, Michalek S, Pastian R, Stein S (1987b) Recombinant avirulent Salmonella for oral immunization to induce mucosal immunity to bacterial pathogens. pp. 261–271 In: Vaccines: New concepts and developments - Proceedings of the Tenth International Convocation on Immunology Kohler H, LoVerde PT(eds) Longman Scientific and Technical, Harlow, Essex, Great BritainGoogle Scholar
  13. Curtiss R III, Kelly SM (1987) Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic. Infect Immun 55:3035–3043PubMedGoogle Scholar
  14. Curtiss R III, Goldschmidt RM, Fletchall NB, Kelly SM (1988a) Avirulent Salmonella typhimurium Acya Δcrp oral vaccine strains expressing a streptococcal colonization and virulence antigen. Vaccine 6:155–160PubMedCrossRefGoogle Scholar
  15. Curtiss R III, Kelly SM, Gulig PA, Gentry-Weeks CR, Galan JE (1988b) Avirulent Salmonella expressing virulence antigens from other pathogens for use as orally-administered vaccines. pp. 311–328 In: Virulence mechanisms of bacterial pathogens. JA Roth (ed) American Society for Microbiology, Washington DCGoogle Scholar
  16. Curtiss R III, Kelly SM, Gulig PA, Nakayama K (1988c) Selective delivery of antigens by recombinant bacteria. Curr Top Microbiol Immun In press.Google Scholar
  17. Curtiss R III, Nakayama K, Kelly SM (1988d) Recombinant avirulent Salmonella vaccine strains with stable maintenance and high level expression of cloned genes in vivo. In: Immunology and Immunopathology of the Alimentary Canal, NY M. Dekker In press.Google Scholar
  18. Dougan G, Sellwood R, Maskell D, Sweeney K, Liew FY, Beesley J, Hormaeche C (1986) In vivo properties of a cloned K88 adherence antigen determinant. Infect Immun 52:344–347PubMedGoogle Scholar
  19. Dougan G, Hormaeche CE, Maskell DJ (1987a) Live oral Salmonella vaccines: potential use of attenuated strains as carriers of heterologous antigens to the immune system. Parasite Immunology 9:151–160PubMedCrossRefGoogle Scholar
  20. Germanier R, Furer E (1971) Immunity in experimental salmonellosis. II. Basis for the avirulence and protective capacity of galE mutants of Salmonella typhimurium. Infect Immun 4:663–673PubMedGoogle Scholar
  21. Germanier R, Furer E (1975) Isolation and characterization of GalE mutant Ty2la of Salmonella typhi: a candidate strain for a live, oral typhoid vaccine. J Infect Dis 131:553–558PubMedCrossRefGoogle Scholar
  22. Goebel W (ed.) (1985) Genetic approaches to microbial pathogenicity. Curr Top Microbiol Immunol. Vol. 118. Springer-Verlag, New YorkGoogle Scholar
  23. Gulig PA, Curtiss III R (1987) Plasmid-associated virulence of Salmonella typhimurium. Infect Immun 55:891–2901Google Scholar
  24. Heffernan EJ, Fierer J, Chikami G, Guiney D (1987) Natural history of oral Salmonella dublin infection in BALB/c mice: effect of an 80-kilobase-pair plasmid on virulence. J Infect Dis 155:1254–1259PubMedCrossRefGoogle Scholar
  25. Hoiseth S, Stocker BAD (1981) Aromatic-dependent Salmonella typhimurium are nonvirulent and effective as live vaccines Nature 291:238–239PubMedCrossRefGoogle Scholar
  26. Holt RG, Abiko Y, Saito S, Smorawinska M, Hansen JB, Curtiss R III (1982) Streptococcus mutans genes that code for extracellular proteins in Escherichia coli K-12. Infect Immun 38:147–156PubMedGoogle Scholar
  27. Jagusztyn-Krynicka EK, Smorawinska M, Curtiss R III (1982) Expression of Streptococcus mutans aspartate semialdehyde dehydrogenase gene cloned into plasmid BR322. J Gen Microbiol 128:1135–1145PubMedGoogle Scholar
  28. Jones GW, Rabert DK, Svinarich DM, Whitfield HJ (1982) Association of adhesive, invasive, and virulent phenotypes of S. typhimurium with autonomous 60-megadalton plasmids. Infect Immun 38:476–486PubMedGoogle Scholar
  29. LeFever ME, Joel DD (1984) Peyer’s patch epithelium: an imperfect barrier pp. 45–56 In: Schiller CM(ed.) Intestinal toxicology. Raven Press, New YorkGoogle Scholar
  30. Macrina FL (1984) Molecular cloning of bacterial antigens and virulence determinants. Annu Rev Microbiol 38:193–219PubMedCrossRefGoogle Scholar
  31. Maskell D, Liew FY, Sweeney K, Dougan G, Hormaeche C (1986) Attenuated Salmonella typhimurium as live oral vaccines and carriers for delivering antigens to the secretory immune system pp. 213–217 In: Vaccines 86. Cold Spring Harbor Laboratory, Cold Spring HarborGoogle Scholar
  32. McCaughan G, Basten A (1983) Immune system of the gastrointestinal tract Internal Rev Physiol 28:131–157Google Scholar
  33. McFarland WC, Stocker BAD (1987) Effect of different purine auxotrophic mutations on mouse-virulence of a Vi-positive strain of Salmonella dublin and of two strains of Salmonella typhimurium. Microbial Pathogenesis 3:129–141PubMedCrossRefGoogle Scholar
  34. McNabb PC, Tomasi TB (1981) Host defense mechanisms at mucosal surfaces. Ann Rev Microbiol 35:477–496CrossRefGoogle Scholar
  35. Miller JH (1972) Experiments in Molecular Genetics Cold Spring Harbor Laboratory, Cold Spring Harbor, NYGoogle Scholar
  36. Nakamura M, Sato S, Ohya T, Suzuki S , Ikeda S , Koeda T (1985) Plasmidcured Salmonella enteritidis AL1192 as a candidate for a live vaccine . Infect Immun 50 : 586–587PubMedGoogle Scholar
  37. Nakayama K, Kelly SM, Curtiss III R (1988) Construction of an Asd+ expression-cloning vector: stable maintenance and high level expression of cloned genes in a Salmonella vaccine strain. Bio/Technology 6 : 693–697CrossRefGoogle Scholar
  38. Pardon P, Popoff MY, Coynault C, Marly J, Miras I (1986) Virulenceassociated plasmids of Salmonella serotype typhimurium in experimental murine infection. Ann Microbiol (Paris) 137B:47–60Google Scholar
  39. Reed LJ, Muench H (1938) A simple method of estimating fifty percent endpoints. Am J Hyg 27:493–497Google Scholar
  40. Urbaschek B (1987) Perspectives on bacterial pathogenesis and host defense. In Reviews of Infectious Diseases, Volume 9, Supplement 5. Infectious Diseases Society of America, the University of Chicago Press, ChicagoGoogle Scholar
  41. Weisz-Carrington P, Roux M, McWilliams M, Phillips-Quagliata JM, Lamm ME (1979) Organ and isotype distribution of plasma cells producing specific antibody after oral immunization: Evidence for a generalized secretory immune system. J Immunol 123:1705–1708(1979)PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Roy CurtissIII
    • 1
  • Sandra M. Kelly
    • 1
  • Paul A. Gulig
    • 1
    • 2
  • Koji Nakayama
    • 1
    • 3
  1. 1.Department of BiologyWashington UniversitySt. LouisUSA
  2. 2.Dept. of Immunology and Medical MicrobiologyUniversity of Florida College of MedicineGainesvilleUSA
  3. 3.Dept. of Microbiology, School of DentistryKyushu UniversityHigashi-ku Fukuoka 812Japan

Personalised recommendations