Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1995 Jul;63(7):2564–2569. doi: 10.1128/iai.63.7.2564-2569.1995

Influence of preimmunization with tetanus toxoid on immune responses to tetanus toxin fragment C-guest antigen fusions in a Salmonella vaccine carrier.

J A Chabalgoity 1, B Villareal-Ramos 1, C M Khan 1, S N Chatfield 1, R D de Hormaeche 1, C E Hormaeche 1
PMCID: PMC173343  PMID: 7790070

Abstract

We have previously described a new system for the delivery of recombinant antigens in live Salmonella vaccines as genetic fusions to the C terminus of fragment C of tetanus toxin (TetC) driven by the anaerobically inducible nirB promoter. It has been reported that preimmunization with tetanus toxoid (TT) can suppress the antibody response to peptides chemically coupled to TT (epitope-specific suppression) in both animals and humans, which could interfere with efficacy of the Salmonella-TetC delivery system. We report that preimmunization of BALB/c mice with TT in alum did not suppress the response to either of two protective antigens of Schistosoma mansoni, the full-length S. mansoni P28 glutathione S-transferase (P28) and a construct consisting of eight tandem copies of the protective peptide comprising amino acids 115 to 131 of P28. The guest antigens were expressed in the aroA Salmonella typhimurium SL3261 vaccine strain as fusions to TetC. Preimmunization with TT 10 weeks before administration of the recombinant salmonellae did not alter the antibody response to the full-length P28, whereas the response to the peptide comprising amino acids 115 to 131 was increased by preimmunization with TT, with the increase seen mainly in the immunoglobulin G1 isotype. The antitetanus response was increased by preimmunization with TT in all groups receiving salmonellae expressing TetC. The results could be important when one is considering the use of the Salmonella-TetC delivery system in populations preimmunized with TT.

Full Text

The Full Text of this article is available as a PDF (201.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bao J. X., Clements J. D. Prior immunologic experience potentiates the subsequent antibody response when Salmonella strains are used as vaccine carriers. Infect Immun. 1991 Oct;59(10):3841–3845. doi: 10.1128/iai.59.10.3841-3845.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chatfield S. N., Charles I. G., Makoff A. J., Oxer M. D., Dougan G., Pickard D., Slater D., Fairweather N. F. 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 Aug;10(8):888–892. doi: 10.1038/nbt0892-888. [DOI] [PubMed] [Google Scholar]
  3. Cooper G. L., Nicholas R. A., Cullen G. A., Hormaeche C. E. Vaccination of chickens with a Salmonella enteritidis aroA live oral Salmonella vaccine. Microb Pathog. 1990 Oct;9(4):255–265. doi: 10.1016/0882-4010(90)90014-h. [DOI] [PubMed] [Google Scholar]
  4. Cooper G. L., Venables L. M., Nicholas R. A., Cullen G. A., Hormaeche C. E. Vaccination of chickens with chicken-derived Salmonella enteritidis phage type 4 aroA live oral Salmonella vaccines. Vaccine. 1992;10(4):247–254. doi: 10.1016/0264-410x(92)90160-l. [DOI] [PubMed] [Google Scholar]
  5. Di John D., Wasserman S. S., Torres J. R., Cortesia M. J., Murillo J., Losonsky G. A., Herrington D. A., Stürcher D., Levine M. M. Effect of priming with carrier on response to conjugate vaccine. Lancet. 1989 Dec 16;2(8677):1415–1418. doi: 10.1016/s0140-6736(89)92033-3. [DOI] [PubMed] [Google Scholar]
  6. Etlinger H. M., Gillessen D., Lahm H. W., Matile H., Schönfeld H. J., Trzeciak A. Use of prior vaccinations for the development of new vaccines. Science. 1990 Jul 27;249(4967):423–425. doi: 10.1126/science.1696030. [DOI] [PubMed] [Google Scholar]
  7. Etlinger H. M., Knorr R. Model using a peptide with carrier function for vaccination against different pathogens. Vaccine. 1991 Jul;9(7):512–514. doi: 10.1016/0264-410x(91)90038-8. [DOI] [PubMed] [Google Scholar]
  8. Hackett J. Salmonella-based vaccines. Vaccine. 1990 Feb;8(1):5–11. doi: 10.1016/0264-410x(90)90169-m. [DOI] [PubMed] [Google Scholar]
  9. Herrington D. A., Clyde D. F., Losonsky G., Cortesia M., Murphy J. R., Davis J., Baqar S., Felix A. M., Heimer E. P., Gillessen D. Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites. Nature. 1987 Jul 16;328(6127):257–259. doi: 10.1038/328257a0. [DOI] [PubMed] [Google Scholar]
  10. Herzenberg L. A., Tokuhisa T. Epitope-specific regulation. I. Carrier-specific induction of suppression for IgG anti-hapten antibody responses. J Exp Med. 1982 Jun 1;155(6):1730–1740. doi: 10.1084/jem.155.6.1730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Herzenberg L. A., Tokuhisa T., Hayakawa K., Herzenberg L. A. Lack of immune response gene control for induction of epitope-specific suppression by TGAL antigen. Nature. 1982 Jan 28;295(5847):329–331. doi: 10.1038/295329a0. [DOI] [PubMed] [Google Scholar]
  12. Herzenberg L. A., Tokuhisa T., Herzenberg L. A. Carrier-priming leads to hapten-specific suppression. Nature. 1980 Jun 26;285(5767):664–667. doi: 10.1038/285664a0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Khan C. M., Villarreal-Ramos B., Pierce R. J., Demarco de Hormaeche R., McNeill H., Ali T., Chatfield S., Capron A., Dougan G., Hormaeche C. E. Construction, expression, and immunogenicity of multiple tandem copies of the Schistosoma mansoni peptide 115-131 of the P28 glutathione S-transferase expressed as C-terminal fusions to tetanus toxin fragment C in a live aro-attenuated vaccine strain of Salmonella. J Immunol. 1994 Dec 15;153(12):5634–5642. [PubMed] [Google Scholar]
  15. Khan C. M., Villarreal-Ramos B., Pierce R. J., Riveau G., Demarco de Hormaeche R., McNeill H., Ali T., Fairweather N., Chatfield S., Capron A. Construction, expression, and immunogenicity of the Schistosoma mansoni P28 glutathione S-transferase as a genetic fusion to tetanus toxin fragment C in a live Aro attenuated vaccine strain of Salmonella. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11261–11265. doi: 10.1073/pnas.91.23.11261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lise L. D., Mazier D., Jolivet M., Audibert F., Chedid L., Schlesinger D. Enhanced epitopic response to a synthetic human malarial peptide by preimmunization with tetanus toxoid carrier. Infect Immun. 1987 Nov;55(11):2658–2661. doi: 10.1128/iai.55.11.2658-2661.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mukkur T. K., McDowell G. H., Stocker B. A., Lascelles A. K. Protection against experimental salmonellosis in mice and sheep by immunisation with aromatic-dependent Salmonella typhimurium. J Med Microbiol. 1987 Aug;24(1):11–19. doi: 10.1099/00222615-24-1-11. [DOI] [PubMed] [Google Scholar]
  18. Panina-Bordignon P., Tan A., Termijtelen A., Demotz S., Corradin G., Lanzavecchia A. Universally immunogenic T cell epitopes: promiscuous binding to human MHC class II and promiscuous recognition by T cells. Eur J Immunol. 1989 Dec;19(12):2237–2242. doi: 10.1002/eji.1830191209. [DOI] [PubMed] [Google Scholar]
  19. Peeters C. C., Tenbergen-Meekes A. M., Poolman J. T., Beurret M., Zegers B. J., Rijkers G. T. Effect of carrier priming on immunogenicity of saccharide-protein conjugate vaccines. Infect Immun. 1991 Oct;59(10):3504–3510. doi: 10.1128/iai.59.10.3504-3510.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Robertsson J. A., Fossum C., Svenson S. B., Lindberg A. A. Salmonella typhimurium infection in calves: specific immune reactivity against O-antigenic polysaccharide detectable in in vitro assays. Infect Immun. 1982 Aug;37(2):728–736. doi: 10.1128/iai.37.2.728-736.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sad S., Gupta H. M., Talwar G. P., Raghupathy R. Carrier-induced suppression of the antibody response to a 'self' hapten. Immunology. 1991 Oct;74(2):223–227. [PMC free article] [PubMed] [Google Scholar]
  23. Sad S., Rao K., Arora R., Talwar G. P., Raghupathy R. Bypass of carrier-induced epitope-specific suppression using a T-helper epitope. Immunology. 1992 Aug;76(4):599–603. [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Schutze M. P., Deriaud E., Przewlocki G., LeClerc C. Carrier-induced epitopic suppression is initiated through clonal dominance. J Immunol. 1989 Apr 15;142(8):2635–2640. [PubMed] [Google Scholar]
  26. Schutze M. P., Leclerc C., Jolivet M., Audibert F., Chedid L. Carrier-induced epitopic suppression, a major issue for future synthetic vaccines. J Immunol. 1985 Oct;135(4):2319–2322. [PubMed] [Google Scholar]
  27. Schutze M. P., Leclerc C., Vogel F. R., Chedid L. Epitopic suppression in synthetic vaccine models: analysis of the effector mechanisms. Cell Immunol. 1987 Jan;104(1):79–90. doi: 10.1016/0008-8749(87)90008-6. [DOI] [PubMed] [Google Scholar]
  28. Sjöstedt A., Sandström G., Tärnvik A. Humoral and cell-mediated immunity in mice to a 17-kilodalton lipoprotein of Francisella tularensis expressed by Salmonella typhimurium. Infect Immun. 1992 Jul;60(7):2855–2862. doi: 10.1128/iai.60.7.2855-2862.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sjöstedt A., Sandström G., Tärnvik A. Immunization of mice with an attenuated Salmonella typhimurium strain expressing a membrane protein of Francisella tularensis. A model for identification of bacterial determinants relevant to the host defence against tularemia. Res Microbiol. 1990 Sep-Oct;141(7-8):887–891. doi: 10.1016/0923-2508(90)90126-b. [DOI] [PubMed] [Google Scholar]
  30. Smith B. P., Reina-Guerra M., Hoiseth S. K., Stocker B. A., Habasha F., Johnson E., Merritt F. Aromatic-dependent Salmonella typhimurium as modified live vaccines for calves. Am J Vet Res. 1984 Jan;45(1):59–66. [PubMed] [Google Scholar]
  31. Stocker B. A. Aromatic-dependent Salmonella as live vaccine presenters of foreign epitopes as inserts in flagellin. Res Microbiol. 1990 Sep-Oct;141(7-8):787–796. doi: 10.1016/0923-2508(90)90112-4. [DOI] [PubMed] [Google Scholar]
  32. Valmori D., Pessi A., Bianchi E., Corradin G. Use of human universally antigenic tetanus toxin T cell epitopes as carriers for human vaccination. J Immunol. 1992 Jul 15;149(2):717–721. [PubMed] [Google Scholar]
  33. Wolowczuk I., Auriault C., Bossus M., Boulanger D., Gras-Masse H., Mazingue C., Pierce R. J., Grezel D., Reid G. D., Tartar A. Antigenicity and immunogenicity of a multiple peptidic construction of the Schistosoma mansoni Sm-28 GST antigen in rat, mouse, and monkey. 1. Partial protection of Fischer rat after active immunization. J Immunol. 1991 Mar 15;146(6):1987–1995. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES