Article

Vaccine potential of attenuated mutants of Corynebacterium pseudotuberculosis in sheep.

CRC for Vaccine Technology and Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.
Infection and Immunity (Impact Factor: 4.07). 03/1998; 66(2):474-9.
Source: PubMed

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-gamma)-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-gamma-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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    ABSTRACT: Caseous lymphadenitis (CLA) is a chronic disease that affects sheep and goats worldwide, and its etiological agent is Corynebacterium pseudotuberculosis. Despite the economic losses caused by CLA, there is little information about the molecular mechanisms of bacterial pathogenesis, and current immune prophylaxis against infection has been unable to reduce the incidence of CLA in goats. Recently, 21 different mutant strains of C. pseudotuberculosis were identified by random mutagenesis. In this study, these previously generated mutants were used in mice vaccination trials to develop new immunogens against CLA. Based on this analysis, CZ171053, an iron-acquisition-deficient mutant strain, was selected. After challenge with a virulent strain, 80% of the animals that were immunized with the CZ171053 strain survived. Furthermore, this vaccination elicited both humoral and cellular responses. Intracellular survival of the bacterium was determined using murine J774 cells; in this assay, the CZ171053 had reduced intracellular viability. Because iron acquisition in intracellular bacteria is considered one of their most important virulence factors during infection, these results demonstrate the immunogenic potential of this mutant against CLA.
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    ABSTRACT: Morel's disease (MD), caused by Staphylococcus aureus subspecies anaerobius and caseous lymphadenitis (CLA), caused by Corynebacterium pseudotuberculosis are two of the major constraints of sheep and goats industry. CLA is prevailing in most parts of the world including USA and Europe, while MD is prevailing in some African and Asian countries including Kingdom of Saudi Arabia (KSA), plus some reports of outbreaks in some European countries. In spite of some differences in epidemiology and characteristics of abscesses in the two diseases and easy microscopic differentiation, MD is greatly misdiagnosed as CLA in KSA and elsewhere. Chronic and generally subclinical and contagious nature of infections and in-efficiency of drug therapy besides poor response to available vaccines which are targeting only CLA make the control difficult and prevalence high. This article reviews the main features of epidemiology, virulence factors, clinical manifestations, diagnosis and control measures of these two diseases. It is intended to display the differences between the two diseases and that the MD is at least should have the same importance as CLA in KSA; and to ensure the importance of development of a bivalent vaccine. Quality of the putative vaccine is discussed here. This review is the first for MD and for MD and CLA together.
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