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Title: Effects of Mycobacterium vaccae NCTC 11659 (standard or recombinant) on cytokine production by human and murine cells
Author: Bayley, Elaine Anne
ISNI:       0000 0001 3452 082X
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1999
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Killed M. vaccae is in clinical trials as an immunotherapeutic agent and adjuvant, but understanding of its mode of action is incomplete. To test its potential as a recombinant carrier organism and the nature of the responses evoked, recombinant strains were generated that expressed p27 of SFV. In mice these primed for specific production of IFNγ in the presence of p27, and induced serum IgG2a and, at higher doses, IgG1 responses to M. vaccae sonicate. Flow cytometry for intracellular cytokines after a single subcutaneous injection of 109 M. vaccae revealed accumulation of IFNγ-secreting CD8+ cells in lymph nodes. This finding, together with data generated simultaneously by another research group, implied an unusual adjuvant effect, not shared by other killed mycobacteria. In order to investigate this adjuvanticity the effects of killed M. vaccae on cytokine release from the human THP-1 monocyte line were investigated. M. vaccae, BCG and soluble bacterial preparations were all able to induce IL-12, IL-10 and TNFγ production in vitro to varying extents. Dose of mycobacterium and the addition of IFNγ influenced the balance of cytokines. Attempts to define active components in the IL-12 induction system were not successful, but it was noted that M. vaccae differed strikingly from the other killed mycobacteria in that its induction of IL-12 was greatly enhanced by exposure to lysozyme. The induction of IL-12 proved sufficiently reproducible to be used as a potency assay for material manufactured for clinical use. In conclusion, M. vaccae has been shown to be a potent Th1 inducer at appropriate doses, with the added ability to induce expansion of the CD8+ IFNγ+ population, perhaps via IL-12 release following exposure to lysozyme in vivo. CD8+ cells are strongly implicated in the clinical situations where M. vaccae has shown benefit.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available