1887

Abstract

is a Gram-positive intracellular pathogen that is responsible for listeriosis, a potentially fatal, food-borne illness. Due to its cytoplasmic location during infection, this pathogen can mediate a long-lasting cellular immune response, which makes attenuated strains strong candidates for vaccine development. Recently, our group identified and characterized (Fur-regulated virulence factor A), and deletion of this gene resulted in disruption of iron homeostasis and a strong attenuation in virulence. Despite significant attenuation in the mouse infection model, the mutant was capable of intracellular growth in antigen-presenting cells. Indeed, mice immunized with Δ were able to effectively stimulate specific CD8 T cells to the listerial epitopes LLO and P60 at levels comparable with strain EGDe. Most notably, mice immunized with Δ then subsequently challenged with the wild-type strain were completely protected from listerial infection. On the basis of these results, we advocate the use of Δ as a live attenuated listerial vaccine, and propose that this mutant may serve as a platform for the development of a future vaccine delivery vehicle.

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2013-02-01
2020-08-10
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References

  1. Álvarez B., Álvarez J., Menéndez A., Guijarro J. A. 2008; A mutant in one of two exbD loci of a TonB system in Flavobacterium psychrophilum shows attenuated virulence and confers protection against cold water disease. Microbiology 154:1144–1151 [CrossRef][PubMed]
    [Google Scholar]
  2. Angelakopoulos H., Loock K., Sisul D. M., Jensen E. R., Miller J. F., Hohmann E. L. 2002; Safety and shedding of an attenuated strain of Listeria monocytogenes with a deletion of actA/plcB in adult volunteers: a dose escalation study of oral inoculation. Infect Immun 70:3592–3601 [CrossRef][PubMed]
    [Google Scholar]
  3. Bahey-El-Din M., Casey P. G., Griffin B. T., Gahan C. G. 2008; Lactococcus lactis-expressing listeriolysin O (LLO) provides protection and specific CD8+ T cells against Listeria monocytogenes in the murine infection model. Vaccine 26:5304–5314 [CrossRef][PubMed]
    [Google Scholar]
  4. Bahey-El-Din M., Casey P. G., Griffin B. T., Gahan C. G. 2010; Expression of two Listeria monocytogenes antigens (P60 and LLO) in Lactococcus lactis and examination for use as live vaccine vectors. J Med Microbiol 59:904–912 [CrossRef][PubMed]
    [Google Scholar]
  5. Busch D. H., Pilip I. M., Vijh S., Pamer E. G. 1998; Coordinate regulation of complex T cell populations responding to bacterial infection. Immunity 8:353–362 [CrossRef][PubMed]
    [Google Scholar]
  6. Cabanes D., Dehoux P., Dussurget O., Frangeul L., Cossart P. 2002; Surface proteins and the pathogenic potential of Listeria monocytogenes . Trends Microbiol 10:238–245 [CrossRef][PubMed]
    [Google Scholar]
  7. Carvalho L. H., Hafalla J. C. R., Zavala F. 2001; ELISPOT assay to measure antigen-specific murine CD8+ T cell responses. J Immunol Methods 252:207–218 [CrossRef][PubMed]
    [Google Scholar]
  8. Domínguez-Bernal G., Tierrez A., Bartolomé A., Martínez-Pulgarín S., Salguero F. J., Antonio Orden J., de la Fuente R. 2008; Salmonella enterica serovar Choleraesuis derivatives harbouring deletions in rpoS and phoP regulatory genes are attenuated in pigs, and survive and multiply in porcine intestinal macrophages and fibroblasts, respectively. Vet Microbiol 130:298–311 [CrossRef][PubMed]
    [Google Scholar]
  9. Edelson B. T., Unanue E. R. 2000; Immunity to Listeria infection. Curr Opin Immunol 12:425–431 [CrossRef][PubMed]
    [Google Scholar]
  10. Fouts T. R., DeVico A. L., Onyabe D. Y., Shata M. T., Bagley K. C., Lewis G. K., Hone D. M. 2003; Progress toward the development of a bacterial vaccine vector that induces high-titer long-lived broadly neutralizing antibodies against HIV-1. FEMS Immunol Med Microbiol 37:129–134 [CrossRef][PubMed]
    [Google Scholar]
  11. Glaser P., Frangeul L., Buchrieser C., Rusniok C., Amend A., Baquero F., Berche P., Bloecker H., Brandt P. other authors 2001; Comparative genomics of Listeria species. Science 294:849–852[PubMed]
    [Google Scholar]
  12. Hess J., Gentschev I., Miko D., Welzel M., Ladel C., Goebel W., Kaufmann S. H. 1996; Superior efficacy of secreted over somatic antigen display in recombinant Salmonella vaccine induced protection against listeriosis. Proc Natl Acad Sci U S A 93:1458–1463 [CrossRef][PubMed]
    [Google Scholar]
  13. Jiang S., Rasmussen R. A., Nolan K. M., Frankel F. R., Lieberman J., McClure H. M., Williams K. M., Babu U. S., Raybourne R. B. other authors 2007; Live attenuated Listeria monocytogenes expressing HIV Gag: immunogenicity in rhesus monkeys. Vaccine 25:7470–7479 [CrossRef][PubMed]
    [Google Scholar]
  14. Kaufmann S. H. E. 1993; Immunity to intracellular bacteria. Annu Rev Immunol 11:129–163 [CrossRef][PubMed]
    [Google Scholar]
  15. Kotton C. N., Hohmann E. L. 2004; Enteric pathogens as vaccine vectors for foreign antigen delivery. Infect Immun 72:5535–5547 [CrossRef][PubMed]
    [Google Scholar]
  16. Kuklin N. A., Clark D. J., Secore S., Cook J., Cope L. D., McNeely T., Noble L., Brown M. J., Zorman J. K. other authors 2006; A novel Staphylococcus aureus vaccine: iron surface determinant B induces rapid antibody responses in rhesus macaques and specific increased survival in a murine S. aureus sepsis model. Infect Immun 74:2215–2223 [CrossRef][PubMed]
    [Google Scholar]
  17. Lieberman J., Frankel F. R. 2002; Engineered Listeria monocytogenes as an AIDS vaccine. Vaccine 20:2007–2010 [CrossRef][PubMed]
    [Google Scholar]
  18. Loeffler D. I., Schoen C. U., Goebel W., Pilgrim S. 2006; Comparison of different live vaccine strategies in vivo for delivery of protein antigen or antigen-encoding DNA and mRNA by virulence-attenuated Listeria monocytogenes . Infect Immun 74:3946–3957 [CrossRef][PubMed]
    [Google Scholar]
  19. Maas A., Jacobsen I. D., Meens J., Gerlach G. F. 2006; Use of an Actinobacillus pleuropneumoniae multiple mutant as a vaccine that allows differentiation of vaccinated and infected animals. Infect Immun 74:4124–4132 [CrossRef][PubMed]
    [Google Scholar]
  20. Maciag P. C., Radulovic S., Rothman J. 2009; The first clinical use of a live-attenuated Listeria monocytogenes vaccine: a phase I safety study of Lm-LLO-E7 in patients with advanced carcinoma of the cervix. Vaccine 27:3975–3983 [CrossRef][PubMed]
    [Google Scholar]
  21. McLaughlin H. P., Hill C., Gahan C. G. M. 2011; The impact of iron on Listeria monocytogenes; inside and outside the host. Curr Opin Biotechnol 22:194–199 [CrossRef][PubMed]
    [Google Scholar]
  22. McLaughlin H. P., Xiao Q., Rea R. B., Pi H., Casey P. G., Darby T., Charbit A., Sleator R. D., Joyce S. A. other authors 2012; A putative P-type ATPase required for virulence and resistance to haem toxicity in Listeria monocytogenes . PLoS ONE 7:e30928 [CrossRef][PubMed]
    [Google Scholar]
  23. Medina E., Guzmán C. A. 2001; Use of live bacterial vaccine vectors for antigen delivery: potential and limitations. Vaccine 19:1573–1580 [CrossRef][PubMed]
    [Google Scholar]
  24. Melief C. J. M. 1992; Tumor eradication by adoptive transfer of cytotoxic T lymphocytes. Adv Cancer Res 58:143–175 [CrossRef][PubMed]
    [Google Scholar]
  25. Nelson K. E., Fouts D. E., Mongodin E. F., Ravel J., DeBoy R. T., Kolonay J. F., Rasko D. A., Angiuoli S. V., Gill S. R. other authors 2004; Whole genome comparisons of serotype 4b and 1/2a strains of the food-borne pathogen Listeria monocytogenes reveal new insights into the core genome components of this species. Nucleic Acids Res 32:2386–2395 [CrossRef][PubMed]
    [Google Scholar]
  26. Pamer E. G. 2004; Immune responses to Listeria monocytogenes . Nat Rev Immunol 4:812–823 [CrossRef][PubMed]
    [Google Scholar]
  27. Pilgrim S., Stritzker J., Schoen C., Kolb-Mäurer A., Geginat G., Loessner M. J., Gentschev I., Goebel W. 2003; Bactofection of mammalian cells by Listeria monocytogenes: improvement and mechanism of DNA delivery. Gene Ther 10:2036–2045 [CrossRef][PubMed]
    [Google Scholar]
  28. Schoen C., Kolb-Mäurer A., Geginat G., Löffler D., Bergmann B., Stritzker J., Szalay A. A., Pilgrim S., Goebel W. 2005; Bacterial delivery of functional messenger RNA to mammalian cells. Cell Microbiol 7:709–724 [CrossRef][PubMed]
    [Google Scholar]
  29. Schoen C., Loeffler D. I., Frentzen A., Pilgrim S., Goebel W., Stritzker J. 2008; Listeria monocytogenes as novel carrier system for the development of live vaccines. Int J Med Microbiol 298:45–58 [CrossRef][PubMed]
    [Google Scholar]
  30. Starks H., Bruhn K. W., Shen H., Barry R. A., Dubensky T. W., Brockstedt D., Hinrichs D. J., Higgins D. E., Miller J. F. other authors 2004; Listeria monocytogenes as a vaccine vector: virulence attenuation or existing antivector immunity does not diminish therapeutic efficacy. J Immunol 173:420–427[PubMed] [CrossRef]
    [Google Scholar]
  31. Stevens R., Lavoy A., Nordone S., Burkhard M., Dean G. A. 2005; Pre-existing immunity to pathogenic Listeria monocytogenes does not prevent induction of immune responses to feline immunodeficiency virus by a novel recombinant Listeria monocytogenes vaccine. Vaccine 23:1479–1490 [CrossRef][PubMed]
    [Google Scholar]
  32. Stritzker J., Janda J., Schoen C., Taupp M., Pilgrim S., Gentschev I., Schreier P., Geginat G., Goebel W. 2004; Growth, virulence, and immunogenicity of Listeria monocytogenes aro mutants. Infect Immun 72:5622–5629 [CrossRef][PubMed]
    [Google Scholar]
  33. Tangney M., Gahan C. G. 2010; Listeria monocytogenes as a vector for anti-cancer therapies. Curr Gene Ther 10:46–55 [CrossRef][PubMed]
    [Google Scholar]
  34. Vijh S., Pamer E. G. 1997; Immunodominant and subdominant CTL responses to Listeria monocytogenes infection. J Immunol 158:3366–3371[PubMed]
    [Google Scholar]
  35. Williams P. H., Rabsch W., Methner U., Voigt W., Tschäpe H., Reissbrodt R. 2006; Catecholate receptor proteins in Salmonella enterica: role in virulence and implications for vaccine development. Vaccine 24:3840–3844 [CrossRef][PubMed]
    [Google Scholar]
  36. Yap K. L., Ada G. L., McKenzie I. F. 1978; Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature 273:238–239 [CrossRef][PubMed]
    [Google Scholar]
  37. Yin Y., Tian D., Jiao H., Zhang C., Pan Z., Zhang X., Wang X., Jiao X. 2011; Pathogenicity and immunogenicity of a mutant strain of Listeria monocytogenes in the chicken infection model. Clin Vaccine Immunol 18:500–505 [CrossRef][PubMed]
    [Google Scholar]
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