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. 1990 Oct 1;172(4):1083–1090. doi: 10.1084/jem.172.4.1083

Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells

PMCID: PMC2188594  PMID: 1698908

Abstract

Oral immunization with an attenuated Salmonella typhimurium recombinant containing the full-length Plasmodium berghei circumsporozoite (CS) gene induces protective immunity against P. berghei sporozoite challenge in the absence of antibody. We found that this immunity was mediated through the induction of specific CD8+ T cells since in vivo elimination of CD8+ cells abrogated protection. In vitro studies revealed that this Salmonella-P. berghei CS recombinant induced class I- restricted CD8+ cytotoxic T cells that are directed against the P. berghei CS peptide epitope spanning amino acids 242-253. This is the same peptide that previously was identified as the target of cytotoxic T lymphocytes (CTL) induced by sporozoite immunization. Salmonella-P. falciparum CS recombinants were constructed that contained either the full-length CS gene or a repeatless gene consisting of CS flanking sequences. Both of these vaccines were able to induce CD8+ CTL directed against P. falciparum CS peptide 371-390, which is identical to the target of CTL induced by sporozoites and vaccinia CS recombinants. These results directly demonstrate the ability of an intracellular bacteria such as Salmonella to induce class I-restricted CD8+ CTL and illustrate the importance of CD8+ CTL in immunity to malaria.

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Selected References

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

  1. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Charoenvit Y., Leef M. F., Yuan L. F., Sedegah M., Beaudoin R. L. Characterization of Plasmodium yoelii monoclonal antibodies directed against stage-specific sporozoite antigens. Infect Immun. 1987 Mar;55(3):604–608. doi: 10.1128/iai.55.3.604-608.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cohen S. N., Chang A. C., Hsu L. Nonchromosomal antibiotic resistance in bacteria: genetic transformation of Escherichia coli by R-factor DNA. Proc Natl Acad Sci U S A. 1972 Aug;69(8):2110–2114. doi: 10.1073/pnas.69.8.2110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Collins F. M. Vaccines and cell-mediated immunity. Bacteriol Rev. 1974 Dec;38(4):371–402. doi: 10.1128/br.38.4.371-402.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  6. Egan J. E., Weber J. L., Ballou W. R., Hollingdale M. R., Majarian W. R., Gordon D. M., Maloy W. L., Hoffman S. L., Wirtz R. A., Schneider I. Efficacy of murine malaria sporozoite vaccines: implications for human vaccine development. Science. 1987 Apr 24;236(4800):453–456. doi: 10.1126/science.3551073. [DOI] [PubMed] [Google Scholar]
  7. FURNESS G. Interaction between Salmonella typhimurium and phagocytic cells in cell culture. J Infect Dis. 1958 Nov-Dec;103(3):272–277. doi: 10.1093/infdis/103.3.272. [DOI] [PubMed] [Google Scholar]
  8. FURNESS G., ROWLEY D. Transduction of virulence within the species Salmonella typhimurium. J Gen Microbiol. 1956 Aug;15(1):140–145. doi: 10.1099/00221287-15-1-140. [DOI] [PubMed] [Google Scholar]
  9. Gross M., Sweet R. W., Sathe G., Yokoyama S., Fasano O., Goldfarb M., Wigler M., Rosenberg M. Purification and characterization of human H-ras proteins expressed in Escherichia coli. Mol Cell Biol. 1985 May;5(5):1015–1024. doi: 10.1128/mcb.5.5.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hoffman S. L., Isenbarger D., Long G. W., Sedegah M., Szarfman A., Waters L., Hollingdale M. R., van der Meide P. H., Finbloom D. S., Ballou W. R. Sporozoite vaccine induces genetically restricted T cell elimination of malaria from hepatocytes. Science. 1989 Jun 2;244(4908):1078–1081. doi: 10.1126/science.2524877. [DOI] [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. Hone D., Attridge S., van den Bosch L., Hackett J. A chromosomal integration system for stabilization of heterologous genes in Salmonella based vaccine strains. Microb Pathog. 1988 Dec;5(6):407–418. doi: 10.1016/0882-4010(88)90002-2. [DOI] [PubMed] [Google Scholar]
  13. Hämmerling G. J., Hämmerling U., Flaherty L. Qat-4 and Qat-5, new murine T-cell antigens governed by the Tla region and identified by monoclonal antibodies. J Exp Med. 1979 Jul 1;150(1):108–116. doi: 10.1084/jem.150.1.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kumar S., Miller L. H., Quakyi I. A., Keister D. B., Houghten R. A., Maloy W. L., Moss B., Berzofsky J. A., Good M. F. Cytotoxic T cells specific for the circumsporozoite protein of Plasmodium falciparum. Nature. 1988 Jul 21;334(6179):258–260. doi: 10.1038/334258a0. [DOI] [PubMed] [Google Scholar]
  15. Lafferty K. J., Andrus L., Prowse S. J. Role of lymphokine and antigen in the control of specific T cell responses. Immunol Rev. 1980;51:279–314. doi: 10.1111/j.1600-065x.1980.tb00325.x. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Lindberg A. A., Robertsson J. A. Salmonella typhimurium infection in calves: cell-mediated and humoral immune reactions before and after challenge with live virulent bacteria in calves given live or inactivated vaccines. Infect Immun. 1983 Aug;41(2):751–757. doi: 10.1128/iai.41.2.751-757.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miller L. H., Howard R. J., Carter R., Good M. F., Nussenzweig V., Nussenzweig R. S. Research toward malaria vaccines. Science. 1986 Dec 12;234(4782):1349–1356. doi: 10.1126/science.2431481. [DOI] [PubMed] [Google Scholar]
  19. Nussenzweig V., Nussenzweig R. S. Development of a sporozoite malaria vaccine. Am J Trop Med Hyg. 1986 Jul;35(4):678–688. doi: 10.4269/ajtmh.1986.35.678. [DOI] [PubMed] [Google Scholar]
  20. Nussenzweig V., Nussenzweig R. S. Rationale for the development of an engineered sporozoite malaria vaccine. Adv Immunol. 1989;45:283–334. doi: 10.1016/s0065-2776(08)60695-1. [DOI] [PubMed] [Google Scholar]
  21. Romero P., Maryanski J. L., Corradin G., Nussenzweig R. S., Nussenzweig V., Zavala F. Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature. 1989 Sep 28;341(6240):323–326. doi: 10.1038/341323a0. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Schafer R., Nacy C. A., Eisenstein T. K. Induction of activated macrophages in C3H/HeJ mice by avirulent Salmonella. J Immunol. 1988 Mar 1;140(5):1638–1644. [PubMed] [Google Scholar]
  24. Schofield L., Villaquiran J., Ferreira A., Schellekens H., Nussenzweig R., Nussenzweig V. Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature. 1987 Dec 17;330(6149):664–666. doi: 10.1038/330664a0. [DOI] [PubMed] [Google Scholar]
  25. Sidberry H., Kaufman B., Wright D. C., Sadoff J. Immunoenzymatic analysis by monoclonal antibodies of bacterial lipopolysaccharides after transfer to nitrocellulose. J Immunol Methods. 1985 Feb 11;76(2):299–305. doi: 10.1016/0022-1759(85)90307-2. [DOI] [PubMed] [Google Scholar]
  26. Stocker B. A., Hoiseth S. K., Smith B. P. Aromatic-dependent "Salmonella sp." as live vaccine in mice and calves. Dev Biol Stand. 1983;53:47–54. [PubMed] [Google Scholar]
  27. Tagliabue A., Nencioni L., Caffarena A., Villa L., Boraschi D., Cazzola G., Cavalieri S. Cellular immunity against Salmonella typhi after live oral vaccine. Clin Exp Immunol. 1985 Nov;62(2):242–247. [PMC free article] [PubMed] [Google Scholar]
  28. Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
  29. Weber J. L., Hockmeyer W. T. Structure of the circumsporozoite protein gene in 18 strains of Plasmodium falciparum. Mol Biochem Parasitol. 1985 Jun;15(3):305–316. doi: 10.1016/0166-6851(85)90092-1. [DOI] [PubMed] [Google Scholar]
  30. Weiss W. R., Sedegah M., Beaudoin R. L., Miller L. H., Good M. F. CD8+ T cells (cytotoxic/suppressors) are required for protection in mice immunized with malaria sporozoites. Proc Natl Acad Sci U S A. 1988 Jan;85(2):573–576. doi: 10.1073/pnas.85.2.573. [DOI] [PMC free article] [PubMed] [Google Scholar]

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