1887

Abstract

The immunogenicity and protective efficacy of a DNA vaccine encoding a genetically inactivated S1 domain of pertussis toxin was evaluated using a murine respiratory challenge model of infection. It was found that mice immunized via the intramuscular route elicited a purely cell-mediated immune response to the DNA vaccine, with high levels of gamma interferon (IFN-) and interleukin (IL)-2 detected in the S1-stimulated splenocyte supernatants and no serum IgG. Despite the lack of an antibody response, the lungs of DNA-immunized mice were cleared of at a significantly faster rate compared with mock-immunized mice following an aerosol challenge. To gauge the true potential of this S1 DNA vaccine, the immune response and protective efficacy of the commercial diphtheria–tetanus–acellular pertussis (DTaP) vaccine were included as the gold standard. Immunization with DTaP elicited a typically strong T-helper (Th)2-polarized immune response with significantly higher titres of serum IgG than in the DNA vaccine group, but a relatively weak Th1 response with low levels of IFN- and IL-2 detected in the supernatants of antigen-stimulated splenocytes. DTaP-immunized mice cleared the aerosol challenge more efficiently than DNA-immunized mice, with no detectable pathogen after day 7 post-challenge.

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2008-01-01
2024-03-28
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References

  1. Barlow W. E., Davis R. L., Glasser J. W., Rhodes P. H., Thompson R. S., Mullooly J. P., Black S. B., Shinefield H. R., Ward J. I. other authors 2001; The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine. N Engl J Med 345:656–661 [CrossRef]
    [Google Scholar]
  2. Barnard A., Mahon B. P., Watkins J., Redhead K., Mills K. H. 1996; Th1/Th2 cell dichotomy in acquired immunity to Bordetella pertussis : variables in the in vivo priming and in vitro cytokine detection techniques affect the classification of T-cell subsets as Th1, Th2 or Th0. Immunology 87:372–380 [CrossRef]
    [Google Scholar]
  3. Barry E. M., Gomez-Duarte O., Chatfield S., Rappuoli R., Pizza M., Losonsky G., Galen J., Levine M. M. 1996; Expression and immunogenicity of pertussis toxin S1 subunit–tetanus toxin fragment C fusions in Salmonella typhi vaccine strain CVD 908. Infect Immun 64:4172–4181
    [Google Scholar]
  4. Boucher P., Sato H., Sato Y., Locht C. 1994; Neutralizing antibodies and immunoprotection against pertussis and tetanus obtained by use of a recombinant pertussis toxin–tetanus toxin fusion protein. Infect Immun 62:449–456
    [Google Scholar]
  5. Castro M. G., McNamara U., Carbonetti N. H. 2001; Expression, activity and cytotoxicity of pertussis toxin S1 subunit in transfected mammalian cells. Cell Microbiol 3:45–54 [CrossRef]
    [Google Scholar]
  6. Chen A. Y., Fry S. R., Forbes-Faulkner J., Daggard G. E., Mukkur T. K. 2006; Comparative immunogenicity of M. hyopneumoniae NrdF encoded in different expression systems delivered orally via attenuated S. typhimurium aro A in mice. Vet Microbiol 114:252–259 [CrossRef]
    [Google Scholar]
  7. Cherry J. D., Grimprel E., Guiso N., Heininger U., Mertsola J. 2005; Defining pertussis epidemiology: clinical, microbiologic and serologic perspectives. Pediatr Infect Dis J 24:Suppl.S25–S34 [CrossRef]
    [Google Scholar]
  8. De Magistris M. T., Romano M., Nuti S., Rappuoli R., Tagliabue A. 1988; Dissecting human T cell responses against Bordetella species. J Exp Med 168:1351–1362 [CrossRef]
    [Google Scholar]
  9. Delogu G., Howard A., Collins F. M., Morris S. L. 2000; DNA vaccination against tuberculosis: expression of a ubiquitin-conjugated tuberculosis protein enhances antimycobacterial immunity. Infect Immun 68:3097–3102 [CrossRef]
    [Google Scholar]
  10. Donnelly J. J., Ulmer J. B., Shiver J. W., Liu M. A. 1997; DNA vaccines. Annu Rev Immunol 15:617–648 [CrossRef]
    [Google Scholar]
  11. Donnelly S., Loscher C. E., Lynch M. A., Mills K. H. 2001; Whole-cell but not acellular pertussis vaccines induce convulsive activity in mice: evidence of a role for toxin-induced interleukin-1 β in a new murine model for analysis of neuronal side effects of vaccination. Infect Immun 69:4217–4223 [CrossRef]
    [Google Scholar]
  12. Gold M. S., Noonan S., Osbourn M., Precepa S., Kempe A. E. 2003; Local reactions after the fourth dose of acellular pertussis vaccine in South Australia. Med J Aust 179:191–194
    [Google Scholar]
  13. Greco D., Salmaso S., Mastrantonio P., Giuliano M., Tozzi A. E., Anemona A., Ciofi degli Atti M. L., Giammanco A., Panei P. other authors 1996; A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. N Engl J Med 334:341–349 [CrossRef]
    [Google Scholar]
  14. Gurunathan S., Klinman D. M., Seder R. A. 2000; DNA vaccines: immunology, application, and optimization. Annu Rev Immunol 18:927–974 [CrossRef]
    [Google Scholar]
  15. Gustafsson L., Hallander H. O., Olin P., Reizenstein E., Storsaeter J. 1996; A controlled trial of a two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine. N Engl J Med 334:349–355 [CrossRef]
    [Google Scholar]
  16. Halperin S. A., Issekutz T. B., Kasina A. 1991; Modulation of Bordetella pertussis infection with monoclonal antibodies to pertussis toxin. J Infect Dis 163:355–361 [CrossRef]
    [Google Scholar]
  17. Imaizumi A., Suzuki Y., Ono S., Sato H., Sato Y. 1983; Heptakis(2,6- O -dimethyl) β -cyclodextrin: a novel growth stimulant for Bordetella pertussis phase I. J Clin Microbiol 17:781–786
    [Google Scholar]
  18. Kamachi K., Arakawa Y. 2004; Expression of a C terminally truncated form of pertussis toxin S1 subunit effectively induces protection against pertussis toxin following DNA-based immunization. Infect Immun 72:4293–4296 [CrossRef]
    [Google Scholar]
  19. Kamachi K., Arakawa Y. 2007; Development of safer pertussis DNA vaccine expressing non-toxic C180 polypeptide of pertussis toxin S1 subunit. Vaccine 25:1000–1006 [CrossRef]
    [Google Scholar]
  20. Kamachi K., Konda T., Arakawa Y. 2003; DNA vaccine encoding pertussis toxin S1 subunit induces protection against Bordetella pertussis in mice. Vaccine 21:4609–4615 [CrossRef]
    [Google Scholar]
  21. Klinman D. M., Yamshchikov G., Ishigatsubo Y. 1997; Contribution of CpG motifs to the immunogenicity of DNA vaccines. J Immunol 158:3635–3639
    [Google Scholar]
  22. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685 [CrossRef]
    [Google Scholar]
  23. Lee S. F., March R. J., Halperin S. A., Faulkner G., Gao L. 1999; Surface expression of a protective recombinant pertussis toxin S1 subunit fragment in Streptococcus gordonii . Infect Immun 67:1511–1516
    [Google Scholar]
  24. Lee S. F., Halperin S. A., Salloum D. F., MacMillan A., Morris A. 2003; Mucosal immunization with a genetically engineered pertussis toxin S1 fragment–cholera toxin subunit B chimeric protein. Infect Immun 71:2272–2275 [CrossRef]
    [Google Scholar]
  25. Mahon B. P., Ryan M. S., Griffin F., Mills K. H. 1996; Interleukin-12 is produced by macrophages in response to live or killed Bordetella pertussis and enhances the efficacy of an acellular pertussis vaccine by promoting induction of Th1 cells. Infect Immun 64:5295–5301
    [Google Scholar]
  26. McGuirk P., Mills K. H. G. 2000; A regulatory role for interleukin 4 in differential inflammatory response in the lung following infection of mice primed with Th1- or Th2-inducing pertussis vaccines. Infect Immun 68:1383–1390 [CrossRef]
    [Google Scholar]
  27. Mills K. H. 2001; Immunity to Bordetella pertussis . Microbes Infect 3:655–677 [CrossRef]
    [Google Scholar]
  28. Mills K. H., Barnard A., Watkins J., Redhead K. 1993; Cell-mediated immunity to Bordetella pertussis : role of Th1 cells in bacterial clearance in a murine respiratory infection model. Infect Immun 61:399–410
    [Google Scholar]
  29. Mills K. H., Ryan M., Ryan E., Mahon B. P. 1998; A murine model in which protection correlates with pertussis vaccine efficacy in children reveals complementary roles for humoral and cell-mediated immunity in protection against Bordetella pertussis . Infect Immun 66:594–602
    [Google Scholar]
  30. Nascimento I. P., Dias W. O., Mazzantini R. P., Miyaji E. N., Gamberini M., Quintilio W., Gebara V. C., Cardoso D. F., Ho P. L. other authors 2000; Recombinant Mycobacterium bovis BCG expressing pertussis toxin subunit S1 induces protection against an intracerebral challenge with live Bordetella pertussis in mice. Infect Immun 68:4877–4883 [CrossRef]
    [Google Scholar]
  31. Nencioni L., Pizza M., Bugnoli M., De Magistris T., Di Tommaso A., Giovannoni F., Manetti R., Marsili I., Matteucci G. other authors 1990; Characterization of genetically inactivated pertussis toxin mutants: candidates for a new vaccine against whooping cough. Infect Immun 58:1308–1315
    [Google Scholar]
  32. Olin P., Rasmussen F., Gustafsson L., Hallander H. O., Heijbel H. for theAd Hoc Group for the Study of Pertussis Vaccines; 1997; Randomised controlled trial of two-component, three-component, and five-component acellular pertussis vaccines compared with whole-cell pertussis vaccine. Lancet 350:1569–1577 [CrossRef]
    [Google Scholar]
  33. Pizza M., Covacci A., Bartoloni A., Perugini M., Nencioni L., De Magistris M. T., Villa L., Nucci D., Manetti R. other authors 1989; Mutants of pertussis toxin suitable for vaccine development. Science 246:497–500 [CrossRef]
    [Google Scholar]
  34. Redhead K., Watkins J., Barnard A., Mills K. H. 1993; Effective immunization against Bordetella pertussis respiratory infection in mice is dependent on induction of cell-mediated immunity. Infect Immun 61:3190–3198
    [Google Scholar]
  35. Rennels M. B., Deloria M. A., Pichichero M. E., Losonsky G. A., Englund J. A., Meade B. D., Anderson E. L., Steinhoff M. C., Edwards K. M. 2000; Extensive swelling after booster doses of acellular pertussis-tetanus-diphtheria vaccines. Pediatrics 105:e12 [CrossRef]
    [Google Scholar]
  36. Rowe J., Yerkovich S. T., Richmond P., Suriyaarachchi D., Fisher E., Feddema L., Loh R., Sly P. D., Holt P. G. 2005; Th2-associated local reactions to the acellular diphtheria-tetanus-pertussis vaccine in 4- to 6-year-old children. Infect Immun 73:8130–8135 [CrossRef]
    [Google Scholar]
  37. Sato Y., Kimura M., Fukumi H. 1984; Development of a pertussis component vaccine in Japan. Lancet 1:122–126
    [Google Scholar]
  38. Sato H., Sato Y., Ohishi I. 1991; Comparison of pertussis toxin (PT)-neutralizing activities and mouse-protective activities of anti-PT mouse monoclonal antibodies. Infect Immun 59:3832–3835
    [Google Scholar]
  39. Schneerson R., Robbins J. B., Taranger J., Lagergard T., Trollfors B. 1996; A toxoid vaccine for pertussis as well as diphtheria? Lessons to be relearned. Lancet 348:1289–1292 [CrossRef]
    [Google Scholar]
  40. Stainer D. W., Scholte M. J. 1970; A simple chemically defined medium for the production of phase I Bordetella pertussis . J Gen Microbiol 63:211–220 [CrossRef]
    [Google Scholar]
  41. Tamura M., Nogimori K., Murai S., Yajima M., Ito K., Katada T., Ui M., Ishii S. 1982; Subunit structure of islet-activating protein, pertussis toxin, in conformity with the A-B model. Biochemistry 21:5516–5522 [CrossRef]
    [Google Scholar]
  42. Tan T., Trindade E., Skowronski D. 2005; Epidemiology of pertussis. Pediatr Infect Dis J 24:Suppl.S10–S18 [CrossRef]
    [Google Scholar]
  43. Ulmer J. B., Donnelly J. J., Parker S. E., Rhodes G. H., Felgner P. L., Dwarki V. J., Gromkowski S. H., Deck R. R., DeWitt C. M. other authors 1993; Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259:1745–1749 [CrossRef]
    [Google Scholar]
  44. van den Berg B. M., David S., Beekhuizen H., Mooi F. R., van Furth R. 2000; Protection and humoral immune responses against Bordetella pertussis infection in mice immunized with acellular or cellular pertussis immunogens. Vaccine 19:1118–1128 [CrossRef]
    [Google Scholar]
  45. Vanderzanden L., Bray M., Fuller D., Roberts T., Custer D., Spik K., Jahrling P., Huggins J., Schmaljohn A., Schmaljohn C. 1998; DNA vaccines expressing either the GP or NP genes of Ebola virus protect mice from lethal challenge. Virology 246:134–144 [CrossRef]
    [Google Scholar]
  46. Walker M. J., Rohde M., Timmis K. N., Guzman C. A. 1992; Specific lung mucosal and systemic immune responses after oral immunization of mice with Salmonella typhimurium aroA , Salmonella typhi Ty21a, and invasive Escherichia coli expressing recombinant pertussis toxin S1 subunit. Infect Immun 60:4260–4268
    [Google Scholar]
  47. Wang R., Doolan D. L., Le T. P., Hedstrom R. C., Coonan K. M., Charoenvit Y., Jones T. R., Hobart P., Margalith M. other authors 1998; Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine. Science 282:476–480 [CrossRef]
    [Google Scholar]
  48. Xing D. K., Das R. G., Williams L., Canthaboo C., Tremmil J., Corbel M. J. 1999; An aerosol challenge model of Bordetella pertussis infection as a potential bioassay for acellular pertussis vaccines. Vaccine 17:565–576 [CrossRef]
    [Google Scholar]
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