1887

Journal of Medical Microbiology logo

Volume 59, Issue 8

Expression of two antigens (P60 and LLO) in and examination for use as live vaccine vectors Free

Abstract

is a food-borne intracellular pathogen that mainly infects pregnant and immunocompromised individuals. The pore-forming haemolysin listeriolysin O (LLO), the main virulence factor of , allows bacteria to escape from the harsh environment of the phagosome to the cytoplasm of the infected cell. This leads to processing of bacterial antigens predominantly through the cytosolic MHC class I presentation pathway. We previously engineered the food-grade bacterium to express LLO and demonstrated an LLO-specific CD8 response upon immunization of mice with the engineered vaccine strains. In the present work, we examined the immune response and protective efficacy of an strain co-expressing LLO and a truncated form of the listerial P60 antigen (tP60). Oral immunization revealed no significant protection against listeriosis with expressing LLO, tP60 or the combined LLO/tP60. In contrast, intraperitoneal vaccination induced an LLO-specific CD8 immune response with LLO-expressing but no significant improvement in protection was observed following vaccination with the combined LLO/tP60 expressing strain. This may be due to the low level of tP60 expression in the LLO/tP60 strain. These results demonstrate the necessity for improved oral vaccination strategies using LLO-expressing vaccine vectors.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): APC, antigen presenting cell , Cm, chloramphenicol , GIT, gastrointestinal tract , GRAS, generally regarded as safe , IFN-γ, gamma interferon , IP, intraperitoneal , LLO, listeriolysin O , LOD, limit of detection , OVA, ovalbumin , RBS, ribosome-binding site , SOE, splicing by overlap extension and Th1, T helper type 1
SGM
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.018770-0
2010-08-01
2024-04-28
Loading full text...

Full text loading...

/deliver/fulltext/jmm/59/8/904.html?itemId=/content/journal/jmm/10.1099/jmm.0.018770-0&mimeType=html&fmt=ahah

References

  1. 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]
     [Google Scholar]
  2. Bahey-El-Din M., Gahan C. G., Griffin B. T. 2010; Lactococcus lactis as a cell factory for delivery of therapeutic proteins. Curr Gene Ther 10:34–45 [CrossRef]
     [Google Scholar]
  3. Carrol M. E., Jackett P. S., Aber V. R., Lowrie D. B. 1979; Phagolysosome formation, cyclic adenosine 3′ : 5′-monophosphate and the fate of Salmonella typhimurium within mouse peritoneal macrophages. J Gen Microbiol 110:421–429 [CrossRef]
     [Google Scholar]
  4. Carvalho L. H., Hafalla J. C., Zavala F. 2001; ELISPOT assay to measure antigen-specific murine CD8+ T cell responses. J Immunol Methods 252:207–218 [CrossRef]
     [Google Scholar]
  5. Darji A., Chakraborty T., Wehland J., Weiss S. 1995; Listeriolysin generates a route for the presentation of exogenous antigens by major histocompatibility complex class I. Eur J Immunol 25:2967–2971 [CrossRef]
     [Google Scholar]
  6. Dietrich G., Hess J., Gentschev I., Knapp B., Kaufmann S. H., Goebel W. 2001; From evil to good: a cytolysin in vaccine development. Trends Microbiol 9:23–28 [CrossRef]
     [Google Scholar]
  7. Faith N. G., Kathariou S., Neudeck B. L., Luchansky J. B., Czuprynski C. J. 2007; A P60 mutant of Listeria monocytogenes is impaired in its ability to cause infection in intragastrically inoculated mice. Microb Pathog 42:237–241 [CrossRef]
     [Google Scholar]
  8. Gasson M. J. 1983; Plasmid complements of Streptococcus lactis NCDO 712 and other lactic streptococci after protoplast-induced curing. J Bacteriol 154:1–9
     [Google Scholar]
  9. 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
     [Google Scholar]
  10. 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]
     [Google Scholar]
  11. Hess J., Grode L., Gentschev I., Fensterle J., Dietrich G., Goebel W., Kaufmann S. H. 2000; Secretion of different listeriolysin cognates by recombinant attenuated Salmonella typhimurium : superior efficacy of haemolytic over non-haemolytic constructs after oral vaccination. Microbes Infect 2:1799–1806 [CrossRef]
     [Google Scholar]
  12. Holo H., Nes I. F. 1989; High-frequency transformation, by electroporation, of Lactococcus lactis subsp. cremoris grown with glycine in osmotically stabilized media. Appl Environ Microbiol 55:3119–3123
     [Google Scholar]
  13. Horton R. M., Cai Z. L., Ho S. N., Pease L. R. 1990; Gene splicing by overlap extension: tailor-made genes using the polymerase chain reaction. Biotechniques 8:528–535
     [Google Scholar]
  14. Huang J. M., La Ragione R. M., Cooley W. A., Todryk S., Cutting S. M. 2008; Cytoplasmic delivery of antigens, by Bacillus subtilis enhances Th1 responses. Vaccine 26:6043–6052 [CrossRef]
     [Google Scholar]
  15. Igwe E. I., Geginat G., Russmann H. 2002; Concomitant cytosolic delivery of two immunodominant listerial antigens by Salmonella enterica serovar Typhimurium confers superior protection against murine listeriosis. Infect Immun 70:7114–7119 [CrossRef]
     [Google Scholar]
  16. Kim W. S., Park J. H., Tandianus J. E., Ren J., Su P., Dunn N. W. 2002; A distinct physiological state of Lactococcus lactis cells that confers survival against a direct and prolonged exposure to severe stresses. FEMS Microbiol Lett 212:203–208 [CrossRef]
     [Google Scholar]
  17. Kimoto H., Nomura M., Kobayashi M., Mizumachi K., Okamoto T. 2003; Survival of lactococci during passage through mouse digestive tract. Can J Microbiol 49:707–711 [CrossRef]
     [Google Scholar]
  18. Kohda C., Kawamura I., Baba H., Nomura T., Ito Y., Kimoto T., Watanabe I., Mitsuyama M. 2002; Dissociated linkage of cytokine-inducing activity and cytotoxicity to different domains of listeriolysin O from Listeria monocytogenes . Infect Immun 70:1334–1341 [CrossRef]
     [Google Scholar]
  19. Kuhn M., Goebel W. 1989; Identification of an extracellular protein of Listeria monocytogenes possibly involved in intracellular uptake by mammalian cells. Infect Immun 57:55–61
     [Google Scholar]
  20. Kuipers O. P., de Ruyter P. G. G. A., Kleerebezem M., de Vos W. M. 1998; Quorum sensing-controlled gene expression in lactic acid bacteria. J Biotechnol 64:15–21 [CrossRef]
     [Google Scholar]
  21. Kunji E. R., Slotboom D. J., Poolman B. 2003; Lactococcus lactis as host for overproduction of functional membrane proteins. Biochim Biophys Acta 161097–108 [CrossRef]
     [Google Scholar]
  22. Le Loir Y., Azevedo V., Oliveira S. C., Freitas D. A., Miyoshi A., Bermúdez-Humarán L. G., Nouaille S., Ribeiro L. A., Leclercq S. other authors 2005; Protein secretion in Lactococcus lactis : an efficient way to increase the overall heterologous protein production. Microb Cell Fact 4:2 [CrossRef]
     [Google Scholar]
  23. Lindholm A., Smeds A., Palva A. 2004; Receptor binding domain of Escherichia coli F18 fimbrial adhesin FedF can be both efficiently secreted and surface displayed in a functional form in Lactococcus lactis . Appl Environ Microbiol 70:2061–2071 [CrossRef]
     [Google Scholar]
  24. Meng J., Doyle M. P. 1997; Emerging issues in microbiological food safety. Annu Rev Nutr 17:255–275 [CrossRef]
     [Google Scholar]
  25. Pamer E. G. 2004; Immune responses to Listeria monocytogenes . Nat Rev Immunol 4:812–823 [CrossRef]
     [Google Scholar]
  26. Piard J. C., Hautefort I., Fischetti V. A., Ehrlich S. D., Fons M., Gruss A. 1997; Cell wall anchoring of the Streptococcus pyogenes M6 protein in various lactic acid bacteria. J Bacteriol 179:3068–3072
     [Google Scholar]
  27. Poquet I., Saint V., Seznec E., Simoes N., Bolotin A., Gruss A. 2000; HtrA is the unique surface housekeeping protease in Lactococcus lactis and is required for natural protein processing. Mol Microbiol 35:1042–1051 [CrossRef]
     [Google Scholar]
  28. Radford K. J., Higgins D. E., Pasquini S., Cheadle E. J., Carta L., Jackson A. M., Lemoine N. R., Vassaux G. 2002; A recombinant E. coli vaccine to promote MHC class I-dependent antigen presentation: application to cancer immunotherapy. Gene Ther 9:1455–1463 [CrossRef]
     [Google Scholar]
  29. Ramaswamy V., Cresence V. M., Rejitha J. S., Lekshmi M. U., Dharsana K. S., Prasad S. P., Vijila H. M. 2007; Listeria – review of epidemiology and pathogenesis. J Microbiol Immunol Infect 40:4–13
     [Google Scholar]
  30. Robinson K., Chamberlain L. M., Schofield K. M., Wells J. M., Le Page R. W. 1997; Oral vaccination of mice against tetanus with recombinant Lactococcus lactis . Nat Biotechnol 15:653–657 [CrossRef]
     [Google Scholar]
  31. Robinson K., Chamberlain L. M., Lopez M. C., Rush C. M., Marcotte H., Le Page R. W., Wells J. M. 2004; Mucosal and cellular immune responses elicited by recombinant Lactococcus lactis strains expressing tetanus toxin fragment C. Infect Immun 72:2753–2761 [CrossRef]
     [Google Scholar]
  32. Stack H. M., Sleator R. D., Bowers M., Hill C., Gahan C. G. 2005; Role for HtrA in stress induction and virulence potential in Listeria monocytogenes . Appl Environ Microbiol 71:4241–4247 [CrossRef]
     [Google Scholar]
  33. Steidler L., Neirynck S., Huyghebaert N., Snoeck V., Vermeire A., Goddeeris B., Cox E., Remon J. P., Remaut E. 2003; Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Nat Biotechnol 21:785–789 [CrossRef]
     [Google Scholar]
  34. Tvinnereim A. R., Hamilton S. E., Harty J. T. 2002; CD8+-T-cell response to secreted and nonsecreted antigens delivered by recombinant Listeria monocytogenes during secondary infection. Infect Immun 70:153–162 [CrossRef]
     [Google Scholar]
  35. van Asseldonk M., Rutten G., Oteman M., Siezen R. J., de Vos W. M., Simons G. 1990; Cloning of usp45 , a gene encoding a secreted protein from Lactococcus lactis subsp. lactis MG1363. Gene 95:155–160 [CrossRef]
     [Google Scholar]
  36. Vazquez-Boland J. A., Kuhn M., Berche P., Chakraborty T., Dominguez-Bernal G., Goebel W., Gonzalez-Zorn B., Wehland J., Kreft J. 2001; Listeria pathogenesis and molecular virulence determinants. Clin Microbiol Rev 14:584–640 [CrossRef]
     [Google Scholar]
  37. Vesa T., Pochart P., Marteau P. 2000; Pharmacokinetics of Lactobacillus plantarum NCIMB 8826, Lactobacillus fermentum KLD, and Lactococcus lactis MG 1363 in the human gastrointestinal tract. Aliment Pharmacol Ther 14:823–828 [CrossRef]
     [Google Scholar]
  38. Vijh S., Pamer E. G. 1997; Immunodominant and subdominant CTL responses to Listeria monocytogenes infection. J Immunol 158:3366–3371
     [Google Scholar]
  39. Watson D., Sleator R. D., Hill C., Gahan C. G. 2008; Enhancing bile tolerance improves survival and persistence of Bifidobacterium and Lactococcus in the murine gastrointestinal tract. BMC Microbiol 8:176 [CrossRef]
     [Google Scholar]
  40. Wells J. M., Mercenier A. 2008; Mucosal delivery of therapeutic and prophylactic molecules using lactic acid bacteria. Nat Rev Microbiol 6:349–362 [CrossRef]
     [Google Scholar]
  41. Wells J. M., Wilson P. W., Norton P. M., Le Page R. W. 1993; A model system for the investigation of heterologous protein secretion pathways in Lactococcus lactis . Appl Environ Microbiol 59:3954–3959
     [Google Scholar]
  42. Wuenscher M. D., Kohler S., Bubert A., Gerike U., Goebel W. 1993; The iap gene of Listeria monocytogenes is essential for cell viability, and its gene product, p60, has bacteriolytic activity. J Bacteriol 175:3491–3501
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.018770-0
Loading
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 (2010); https://doi.org/10.1099/jmm.0.018770-0
/content/journal/jmm/10.1099/jmm.0.018770-0
/content/journal/jmm/10.1099/jmm.0.018770-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error