Harris, Stephanie A; White, Andrew; Stockdale, Lisa; Tanner, Rachel; Sibley, Laura; Sarfas, Charlotte; Meyer, Joel; Peter, Jonathan; O'Shea, Matthew K; Manjaly Thomas, Zita-Rose; +5 more... Hamidi, Ali; Satti, Iman; Dennis, Mike J; McShane, Helen; Sharpe, Sally; (2017) Development of a non-human primate BCG infection model for the evaluation of candidate tuberculosis vaccines. Tuberculosis (Edinburgh, Scotland), 108. pp. 99-105. ISSN 1472-9792 DOI: https://doi.org/10.1016/j.tube.2017.11.006
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Abstract
The lack of validated immunological correlates of protection makes tuberculosis vaccine development difficult and expensive. Using intradermal bacille Calmette-Guréin (BCG) as a surrogate for aerosol Mycobacterium tuberculosis (M.tb) in a controlled human infection model could facilitate vaccine development, but such a model requires preclinical validation. Non-human primates (NHPs) may provide the best model in which to do this. Cynomolgus and rhesus macaques were infected with BCG by intradermal injection. BCG was quantified from a skin biopsy of the infection site and from draining axillary lymph nodes, by culture on solid agar and quantitative polymerase chain reaction. BCG was detected up to 28 days post-infection, with higher amounts of BCG detected in lymph nodes after high dose compared to standard dose infection. Quantifying BCG from lymph nodes of cynomolgus macaques 14 days post-high dose infection showed a significant reduction in the amount of BCG detected in the BCG-vaccinated compared to BCG-naïve animals. Demonstrating a detectable vaccine effect in the lymph nodes of cynomolgus macaques, which is similar in magnitude to that seen in an aerosol M.tb infection model, provides support for proof-of-concept of an intradermal BCG infection model and evidence to support the further evaluation of a human BCG infection model.
Item Type | Article |
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Faculty and Department | Faculty of Infectious and Tropical Diseases > Department of Infection Biology > Dept of Immunology and Infection (-2019) |
Research Centre | TB Centre |
PubMed ID | 29523335 |
ISI | 428112700015 |
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Licence: Creative Commons: Attribution 3.0
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