Vaccine potential of attenuated mutants of Corynebacterium pseudotuberculosis in sheep

Cameron P. Simmons, Sarah J. Dunstan, Mary Jachedjian, Jolanta Krywult, A. L M Hodgson, Richard A. Strugnell

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Corynebacterium pseudotuberculosis, a gram-positive facultative intracellular bacterial pathogen, is the etiological agent of the economically important disease caseous lymphadenitis (CLA) in both sheep and goats. Attenuated mutants of C. pseudotuberculosis have the potential to act as novel vaccines against CLA and as veterinary vaccine vectors. In this report, we have assessed the virulence of both aroQ and pld mutants of C. pseudotuberculosis in sheep and concurrently their capacity to act as vaccines against homologous challenge. The results suggest that aroQ mutants of C. pseudotuberculosis are attenuated with regard to both lymph node persistence and vaccination site reactogenicity. Immunologically, aroQ mutants failed to elicit detectable specific gamma interferon (IFN-γ)- secreting lymphocytes and induced low levels of antibodies to C. pseudotuberculosis culture supernatant antigens. Following subcutaneous vaccination, the immune responses induced by aroQ mutants did not protect sheep from infection with the wild-type strain but did appear to reduce the clinical severity of disease resulting from challenge. Conversely, an attenuated C. pseudotuberculosis strain expressing an enzymatically inactive phospholipase D exotoxin, when used as a vaccine, elicited a protective immune response. Protection appeared to correlate with in vivo persistence of the vaccine strain, the induction of IFN-γ-secreting lymphocytes, and relatively high levels of antibodies to culture supernatant antigens. The results suggest that aroQ mutants of C. pseudotuberculosis may be overly attenuated for use as a CLA vaccines or as vaccine vectors.

Original languageEnglish
Pages (from-to)474-479
Number of pages6
JournalInfection and Immunity
Volume66
Issue number2
Publication statusPublished - 25 Feb 1998

Cite this

Simmons, C. P., Dunstan, S. J., Jachedjian, M., Krywult, J., Hodgson, A. L. M., & Strugnell, R. A. (1998). Vaccine potential of attenuated mutants of Corynebacterium pseudotuberculosis in sheep. Infection and Immunity, 66(2), 474-479.
Simmons, Cameron P. ; Dunstan, Sarah J. ; Jachedjian, Mary ; Krywult, Jolanta ; Hodgson, A. L M ; Strugnell, Richard A. / Vaccine potential of attenuated mutants of Corynebacterium pseudotuberculosis in sheep. In: Infection and Immunity. 1998 ; Vol. 66, No. 2. pp. 474-479.
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abstract = "Corynebacterium pseudotuberculosis, a gram-positive facultative intracellular bacterial pathogen, is the etiological agent of the economically important disease caseous lymphadenitis (CLA) in both sheep and goats. Attenuated mutants of C. pseudotuberculosis have the potential to act as novel vaccines against CLA and as veterinary vaccine vectors. In this report, we have assessed the virulence of both aroQ and pld mutants of C. pseudotuberculosis in sheep and concurrently their capacity to act as vaccines against homologous challenge. The results suggest that aroQ mutants of C. pseudotuberculosis are attenuated with regard to both lymph node persistence and vaccination site reactogenicity. Immunologically, aroQ mutants failed to elicit detectable specific gamma interferon (IFN-γ)- secreting lymphocytes and induced low levels of antibodies to C. pseudotuberculosis culture supernatant antigens. Following subcutaneous vaccination, the immune responses induced by aroQ mutants did not protect sheep from infection with the wild-type strain but did appear to reduce the clinical severity of disease resulting from challenge. Conversely, an attenuated C. pseudotuberculosis strain expressing an enzymatically inactive phospholipase D exotoxin, when used as a vaccine, elicited a protective immune response. Protection appeared to correlate with in vivo persistence of the vaccine strain, the induction of IFN-γ-secreting lymphocytes, and relatively high levels of antibodies to culture supernatant antigens. The results suggest that aroQ mutants of C. pseudotuberculosis may be overly attenuated for use as a CLA vaccines or as vaccine vectors.",
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Simmons, CP, Dunstan, SJ, Jachedjian, M, Krywult, J, Hodgson, ALM & Strugnell, RA 1998, 'Vaccine potential of attenuated mutants of Corynebacterium pseudotuberculosis in sheep' Infection and Immunity, vol. 66, no. 2, pp. 474-479.

Vaccine potential of attenuated mutants of Corynebacterium pseudotuberculosis in sheep. / Simmons, Cameron P.; Dunstan, Sarah J.; Jachedjian, Mary; Krywult, Jolanta; Hodgson, A. L M; Strugnell, Richard A.

In: Infection and Immunity, Vol. 66, No. 2, 25.02.1998, p. 474-479.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Vaccine potential of attenuated mutants of Corynebacterium pseudotuberculosis in sheep

AU - Simmons, Cameron P.

AU - Dunstan, Sarah J.

AU - Jachedjian, Mary

AU - Krywult, Jolanta

AU - Hodgson, A. L M

AU - Strugnell, Richard A.

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AB - Corynebacterium pseudotuberculosis, a gram-positive facultative intracellular bacterial pathogen, is the etiological agent of the economically important disease caseous lymphadenitis (CLA) in both sheep and goats. Attenuated mutants of C. pseudotuberculosis have the potential to act as novel vaccines against CLA and as veterinary vaccine vectors. In this report, we have assessed the virulence of both aroQ and pld mutants of C. pseudotuberculosis in sheep and concurrently their capacity to act as vaccines against homologous challenge. The results suggest that aroQ mutants of C. pseudotuberculosis are attenuated with regard to both lymph node persistence and vaccination site reactogenicity. Immunologically, aroQ mutants failed to elicit detectable specific gamma interferon (IFN-γ)- secreting lymphocytes and induced low levels of antibodies to C. pseudotuberculosis culture supernatant antigens. Following subcutaneous vaccination, the immune responses induced by aroQ mutants did not protect sheep from infection with the wild-type strain but did appear to reduce the clinical severity of disease resulting from challenge. Conversely, an attenuated C. pseudotuberculosis strain expressing an enzymatically inactive phospholipase D exotoxin, when used as a vaccine, elicited a protective immune response. Protection appeared to correlate with in vivo persistence of the vaccine strain, the induction of IFN-γ-secreting lymphocytes, and relatively high levels of antibodies to culture supernatant antigens. The results suggest that aroQ mutants of C. pseudotuberculosis may be overly attenuated for use as a CLA vaccines or as vaccine vectors.

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Simmons CP, Dunstan SJ, Jachedjian M, Krywult J, Hodgson ALM, Strugnell RA. Vaccine potential of attenuated mutants of Corynebacterium pseudotuberculosis in sheep. Infection and Immunity. 1998 Feb 25;66(2):474-479.