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• W2619585973 abstract "Abstract In the absence of a validated correlate of protection or robust animal models for human tuberculosis, Mycobacterial growth inhibition assays (MGIAs) aim to assess vaccines ability to inhibit mycobacterial growth in-vitro . We optimised a reproducible murine splenocyte MGIA based on in-vitro infection with virulent Mycobacterium tuberculosis ( M.tb) Erdman. We identified splenocyte viability as a problem in state-of-art MGIA protocols, which can be improved by simple changes in culture conditions (viability increase from 21% to 46% at last day of culture). The growth inhibitory potential in mice immunised with either BCG, H56:CAF01 or H56:CAF01 administered side-by-side with BCG was significantly better compared to placebo in all groups (0.3 log 10 CFU [±0.2, p = 0.049], 0.5 [±0.2, p = 0.016] and 0.6 [±0.1, p = 0.0007], respectively) corresponding to the levels of in-vivo protection. Unexpectedly the CAF01 adjuvant control group also induced significant growth inhibition of 0.3 log 10 CFU (±0.2, p = 0.047). Finally, we explored vaccine-associated T cell effector functions. Despite presence of high levels of vaccine-specific T cells, we found no increase in CD4 + T cell number or cytokine expression profile, nor a difference in cytokine levels in the supernatant after four days culture with or without M.tb . Spontaneous IFN-γ release correlated with growth inhibition levels (p = 0.02), however the cellular source was not found." @default.
• W2619585973 created "2017-06-05" @default.
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• W2619585973 date "2017-06-06" @default.
• W2619585973 modified "2023-10-04" @default.
• W2619585973 title "Optimisation of a murine splenocyte mycobacterial growth inhibition assay using virulent Mycobacterium tuberculosis" @default.
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• W2619585973 doi "https://doi.org/10.1038/s41598-017-02116-1" @default.
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