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.
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References
Barbieri, J.T. and Cortina, G., 1988, ADP-ribosyltransferase mutations in the catalytic S-1 subunit of pertussis toxin, Infect. Immun., 56:1934–1941.
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.
Cockle, S., 1989, Identification of an active-site residue in subunit S1 of pertussis toxin by photocrosslinking to NAD, FEBS Lett., 249:329–332.
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.
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.
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.
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.
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.
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.
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.
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.
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© 1991 Plenum Press, New York
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Cockle, S. et al. (1991). Development of Non-Toxigenic Vaccine Strains of Bordetella pertussis by Gene Replacement. In: Atassi, M.Z. (eds) Immunobiology of Proteins and Peptides VI. Advances in Experimental Medicine and Biology, vol 303. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-6000-1_24
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DOI: https://doi.org/10.1007/978-1-4684-6000-1_24
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