Caseous lymphadenitis vaccine development: site-specific inactivation of the Corynebacterium pseudotuberculosis phospholipase D gene

Mary Tachedjian, Jolanta Krywult, Robert J. Moore, Adrian L M Hodgson

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

Abstract

Vaccines for ovine caseous lymphadenitis (CLA) are currently formulated using partially purified, formalin inactivated phospholipase D (PLD) derived from Corynebacterium pseudotuberculosis culture supernatants. Chemical treatment has been a common and effective way of inactivating bacterial toxins for use in toxoid vaccines. Genetic inactivation of toxin genes using site-specific mutagenesis has the potential to improve this process by providing a safer and more cost-effective product. In the present study amino acid substitutions at the putative catalytic site and metal binding domain of the PLD protein had a profound affect upon PLD activity and secretion from C. pseudotuberculosis. Two mutated PLD analogues that were secreted to a level of 40% compared to the wild-type and retained minimal activity showed promise for development as recombinant CLA vaccines. Further work will be required to establish their suitability for commercialization.

Original languageEnglish
Pages (from-to)1785-1792
Number of pages8
JournalVaccine
Volume13
Issue number18
DOIs
Publication statusPublished - 1 Jan 1995

Keywords

  • gene expression
  • Genetic toxoid
  • toxin

Cite this

Tachedjian, Mary ; Krywult, Jolanta ; Moore, Robert J. ; Hodgson, Adrian L M. / Caseous lymphadenitis vaccine development : site-specific inactivation of the Corynebacterium pseudotuberculosis phospholipase D gene. In: Vaccine. 1995 ; Vol. 13, No. 18. pp. 1785-1792.
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abstract = "Vaccines for ovine caseous lymphadenitis (CLA) are currently formulated using partially purified, formalin inactivated phospholipase D (PLD) derived from Corynebacterium pseudotuberculosis culture supernatants. Chemical treatment has been a common and effective way of inactivating bacterial toxins for use in toxoid vaccines. Genetic inactivation of toxin genes using site-specific mutagenesis has the potential to improve this process by providing a safer and more cost-effective product. In the present study amino acid substitutions at the putative catalytic site and metal binding domain of the PLD protein had a profound affect upon PLD activity and secretion from C. pseudotuberculosis. Two mutated PLD analogues that were secreted to a level of 40{\%} compared to the wild-type and retained minimal activity showed promise for development as recombinant CLA vaccines. Further work will be required to establish their suitability for commercialization.",
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Caseous lymphadenitis vaccine development : site-specific inactivation of the Corynebacterium pseudotuberculosis phospholipase D gene. / Tachedjian, Mary; Krywult, Jolanta; Moore, Robert J.; Hodgson, Adrian L M.

In: Vaccine, Vol. 13, No. 18, 01.01.1995, p. 1785-1792.

Research output: Contribution to journalArticleResearchpeer-review

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T2 - site-specific inactivation of the Corynebacterium pseudotuberculosis phospholipase D gene

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