Novel Human In Vitro System for Evaluating Antimycobacterial Vaccines

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Abstract
Major research efforts are directed towards the development of a better antimycobacterial vaccine. But progress in the field of tuberculosis vaccine development has been hampered by the lack of human in vitro models to assess vaccine immunogenicity and efficacy. New candidate vaccines will have to be evaluated against the existingMycobacterium bovisBCG “gold standard.” It is therefore important to understand the type of immune responses elicited by BCG vaccination to enable comparisons with potential new candidates. We used a novel human in vitro whole-blood model, which measures immune responses to mycobacteria by use of reporter gene-tagged BCG (BCGlux), to study immune responses to BCG vaccination in 50 neonates in a setting in Cape Town, Republic of South Africa, where tuberculosis is endemic. BCG vaccination significantly reduced growth of BCGluxin whole blood (prevaccination median growth ratio [GR], 9.6; range, 1.3 to 24; postvaccination median GR, 3.9; range, 0.6 to 12.2 [P< 0.0001]). Growth of BCGluxwas better restricted in vaccinated infants than in unvaccinated age-matched controls (n= 4). BCG vaccination induced significantly higher gamma interferon production in response to BCGlux(P< 0.0001) and to purified protein derivative (P= 0.0001). No significant changes in either growth of BCGluxor cytokine production occurred in an adult control group (n= 6) over the study period. The whole-blood luminescence model detects changes in cellular immune responses to mycobacteria induced by BCG vaccination. It is therefore a useful new tool in studying the immunogenicity of newly developed vaccine candidates prior to large field trials assessing efficacy.
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