Advertisement

Development of Non-Toxigenic Vaccine Strains of Bordetella pertussis by Gene Replacement

  • S. Cockle
  • G. Zealey
  • S. Loosmore
  • R. Yacoob
  • R. Fahim
  • Y.-P. Yang
  • G. Jackson
  • H. Boux
  • L. Boux
  • M. Klein
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 303)

Abstract

During the next decade, it is likely that current whole-cell whooping cough vaccines prepared from inactivated Bordetella pertussis will be replaced by component vaccines of defined purity and composition that offer higher efficacy and reduced reactogenicity. The principal B. pertussis antigens under consideration for such vaccines are pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (69 kDa protein) and fimbrial agglutinogens. Although PT is a potent immunogen, it is also a major virulence factor of B. pertussis. However, the chemical treatments now used to inactivate PT can reduce its immunogenicity, and depending on the method used, may be susceptible to reversion. An ideal approach to PT detoxification is the genetic replacement or removal of a few critical functional amino acid residues so that three-dimensional structure and immunogenicity are only minimally impaired.

Keywords

Pertussis Toxin Pertussis Vaccine Bordetella Pertussis Acellular Vaccine Pertussis Antigen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barbieri, J.T. and Cortina, G., 1988, ADP-ribosyltransferase mutations in the catalytic S-1 subunit of pertussis toxin, Infect. Immun., 56:1934–1941.PubMedGoogle Scholar
  2. Burnette, W.N., Cieplak, W., Mar, V.L., Kaljot, K.Y., Sato, H. and Keith, J.M., 1988, Pertussis toxin S1 mutant with reduced enzyme activity and a conserved protective epitope, Science, 242,:72–74.PubMedCrossRefGoogle Scholar
  3. Cockle, S., 1989, Identification of an active-site residue in subunit S1 of pertussis toxin by photocrosslinking to NAD, FEBS Lett., 249:329–332.PubMedCrossRefGoogle Scholar
  4. Cockle, S., Loosmore, S., Radika, K., Zealey, G., Boux, H., Phillips, K. and Klein, M., 1989, Detoxification of pertussis toxin by site-directed mutagenesis, Adv. Exptl. Biol., 251:209–214.Google Scholar
  5. Locht, C., Capiau, C. and Feron, C., 1989, Identification of amino acid residues essential for the enzymatic activities of pertussis toxin, Proc. Natl. Acad. Sci. USA, 86:3075–3079.PubMedCrossRefGoogle Scholar
  6. Loosmore, S.M., Zealey, G.R., Boux, H.A., Cockle, S.A., Radika, K., Fahim, R.E.F., Zobrist, G.J., Yacoob, R.K., Chong, P.C.-S., Yao, F.-L. and Klein, M.H., 1990, Engineering of genetically detoxified pertussis toxin analogues for development of a recombinant whooping cough vaccine, Infect. Immun., 58:3653–3662.PubMedGoogle Scholar
  7. Nencioni, L., Pizza, M., Bugnoli, M., De Magistris, T., Di Tommaso, A., Giovannoni, F., Manetti, R., Marsili, I., Matteucci, G., Nucci, D., Olivieri, R., Pileri, P., Presentini, R., Villa, L., Kreeftenberg, J.G., Silvestri, S., Tagliabue, A. and Rappuoli, R., 1990, Characterization of genetically inactivated pertussis toxin mutants: candidates for a new vaccine against whooping cough, Infect. Immun., 58:1308–1315.PubMedGoogle Scholar
  8. Pizza, M., Bartoloni, A., Prugnola, A., Silvestri, S. and Rappuoli, R., 1988, Subunit S1 of pertussis toxin: mapping of the regions essential for ADP-ribosyltransferase activity, Proc. Nat1. Acad. Sci. USA, 85:7521–7525.CrossRefGoogle Scholar
  9. Pizza, M., Covacci, A., Bartoloni, A., Perugini, M., Nencioni, L., De Magistris, M.T., Villa, L., Nucci, D., Manetti, R., Bugnoli, M., Giovannoni, F., Olivieri, R., Barbieri, J.T., Sato, H. and Rappuoli, R., 1989, Mutants of pertussis toxin suitable for vaccine development, Science, 246:497–500.PubMedCrossRefGoogle Scholar
  10. Tan, U.L., Fahim, R.E.F., Jackson, G., Phillips, K., Wah, P., Alkema, D., Zobrist, G., Herbert, A., Boux, L., Chong, P., Harjee, N., Klein, M. and Vose, J., 1991, A novel process for preparing an acellular pertussis vaccine composed of non-pyrogenic toxoids of pertussis toxin and filamentous hemagglutinin, Molec. Immunol., in press.Google Scholar
  11. Zealey, G.R., Loosmore, S.M., Yacoob, R.K., Cockle, S.A., Boux, L.J., Miller, L.D. and Klein, M.H., 1990, Gene Replacement in Bordetella pertussis by transformation with linear DNA, Bio/Technology, 8:1025–1029.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • S. Cockle
    • 1
  • G. Zealey
    • 1
  • S. Loosmore
    • 1
  • R. Yacoob
    • 1
  • R. Fahim
    • 1
  • Y.-P. Yang
    • 1
  • G. Jackson
    • 1
  • H. Boux
    • 1
  • L. Boux
    • 1
  • M. Klein
    • 1
  1. 1.Connaught Centre for Biotechnology ResearchWillowdaleCanada

Personalised recommendations