Integrating Non-human Primate, Human, and Mathematical Studies to Determine the Influence of BCG Timing on H56 Vaccine Outcomes

Simple item page
dc.contributor.authorJoslyn, Louis R.
dc.contributor.authorSuliman, Sara
dc.contributor.authorKagina, Benjamin M.
dc.contributor.authorScriba, Thomas J.
dc.contributor.authorKirschner, Denise E.
dc.date.accessioned2023-02-14T19:58:30Z
dc.date.available2023-02-14T19:58:30Z
dc.date.issued2018
dc.description.abstractTuberculosis (TB) is the leading cause of death by an infectious agent, and developing an effective vaccine is an important component of the WHO's EndTB Strategy. Non-human primate (NHP) models of vaccination are crucial to TB vaccine development and have informed design of subsequent human trials. However, challenges emerge when translating results from animal models to human applications, and connecting post-vaccination immunological measurements to infection outcomes. The H56:IC31 vaccine is a candidate currently in phase I/IIa trials. H56 is a subunit vaccine that is comprised of 3 mycobacterial antigens: ESAT6, Ag85B, and Rv2660, formulated in IC31 adjuvant. H56, as a boost to Bacillus Calmette-Guérin (BCG, the TB vaccine that is currently used in most countries world-wide) demonstrates improved protection (compared to BCG alone) in mouse and NHP models of TB, and the first human study of H56 reported strong antigen-specific T cell responses to the vaccine. We integrated NHP and human data with mathematical modeling approaches to improve our understanding of NHP and human response to vaccine. We use a mathematical model to describe T-cell priming, proliferation, and differentiation in lymph nodes and blood, and calibrate the model to NHP and human blood data. Using the model, we demonstrate the impact of BCG timing on H56 vaccination response and reveal a general immunogenic response to H56 following BCG prime. Further, we use uncertainty and sensitivity analyses to isolate mechanisms driving differences in vaccination response observed between NHP and human datasets. This study highlights the power of a systems biology approach: integration of multiple modalities to better understand a complex biological system.en_US
dc.identifier.citationJoslyn, L. R., Pienaar, E., DiFazio, R. M., Suliman, S., Kagina, B. M., Flynn, J. L., ... & Kirschner, D. E. (2018). Integrating non-human primate, human, and mathematical studies to determine the influence of BCG timing on H56 vaccine outcomes. Frontiers in Microbiology, 9, 1734.https://doi.org/10.3389/fmicb.2018.01734en_US
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/7801
dc.language.isoenen_US
dc.publisherFrontiers in Microbiologyen_US
dc.subjecttuberculosisen_US
dc.subjectnon-human primateen_US
dc.subjectmathematical modelingen_US
dc.subjectbacillus calmette–guerin (BCG)en_US
dc.subjectvaccinationen_US
dc.titleIntegrating Non-human Primate, Human, and Mathematical Studies to Determine the Influence of BCG Timing on H56 Vaccine Outcomesen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Integrating Non-human Primate, Human, and Mathematical Studies to Determine the Influence of BCG Timing on H56 Vaccine Outcomes.pdf
Size:
6.72 MB
Format:
Adobe Portable Document Format
Description:
Integrating Non-human Primate, Human, and Mathematical Studies to Determine the Influence of BCG Timing on H56 Vaccine Outcomes
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Medical and Health Sciences