Rhodes, Sophie J; Guedj, Jeremie; Fletcher, Helen A; Lindenstrøm, Thomas; Scriba, Thomas J; Evans, Thomas G; Knight, Gwenan M; White, Richard G; (2018) Using vaccine Immunostimulation/Immunodynamic modelling methods to inform vaccine dose decision-making. NPJ Vaccines, 3 (1). 36-. ISSN 2059-0105 DOI: https://doi.org/10.1038/s41541-018-0075-3
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Abstract
Unlike drug dose optimisation, mathematical modelling has not been applied to vaccine dose finding. We applied a novel Immunostimulation/Immunodynamic mathematical modelling framework to translate multi-dose TB vaccine immune responses from mice, to predict most immunogenic dose in humans. Data were previously collected on IFN-γ secreting CD4+ T cells over time for novel TB vaccines H56 and H1 adjuvanted with IC31 in mice (1 dose groups (0.1-1.5 and 15 μg H56 + IC31), 45 mice) and humans (1 dose (50 μg H56/H1 + IC31), 18 humans). A two-compartment mathematical model, describing the dynamics of the post-vaccination IFN-γ T cell response, was fitted to mouse and human data, separately, using nonlinear mixed effects methods. We used these fitted models and a vaccine dose allometric scaling assumption, to predict the most immunogenic human dose. Based on the changes in model parameters by mouse H56 + IC31 dose and by varying the H56 dose allometric scaling factor between mouse and humans, we established that, at a late time point (224 days) doses of 0.8-8 μg H56 + IC31 in humans may be the most immunogenic. A 0.8-8 μg of H-series TB vaccines in humans, may be as, or more, immunogenic, as larger doses. The Immunostimulation/Immunodynamic mathematical modelling framework is a novel, and potentially revolutionary tool, to predict most immunogenic vaccine doses, and accelerate vaccine development.
Item Type | Article |
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Faculty and Department |
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology (-2023) Faculty of Infectious and Tropical Diseases > Department of Infection Biology Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology & Dynamics (2023-) |
Research Centre |
TB Modelling Group Vaccine Centre |
PubMed ID | 30245860 |
ISI | 444837200001 |
Related URLs |
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