Scientific article
Open access

Application of modeling approaches to explore vaccine adjuvant mode-of-action

Published inFrontiers in Immunology, vol. 10, 2150
Publication date2019

Novel adjuvant technologies have a key role in the development of next-generation vaccines, due to their capacity to modulate the duration, strength and quality of the immune response. The AS01 adjuvant is used in the malaria vaccine RTS,S/AS01 and in the licensed herpes-zoster vaccine (Shingrix) where the vaccine has proven its ability to generate protective responses with both robust humoral and T-cell responses. For many years, animal models have provided insights into adjuvant mode-of-action (MoA), generally through investigating individual genes or proteins. Furthermore, modeling and simulation techniques can be utilized to integrate a variety of different data types; ranging from serum biomarkers to large scale "omics" datasets. In this perspective we present a framework to create a holistic integration of pre-clinical datasets and immunological literature in order to develop an evidence-based hypothesis of AS01 adjuvant MoA, creating a unified view of multiple experiments. Furthermore, we highlight how holistic systems-knowledge can serve as a basis for the construction of models and simulations supporting exploration of key questions surrounding adjuvant MoA. Using the Systems-Biology-Graphical-Notation, a tool for graphical representation of biological processes, we have captured high-level cellular behaviors and interactions, and cytokine dynamics during the early immune response, which are substantiated by a series of diagrams detailing cellular dynamics. Through explicitly describing AS01 MoA we have built a consensus of understanding across multiple experiments, and so we present a framework to integrate modeling approaches into exploring adjuvant MoA, in order to guide experimental design, interpret results and inform rational design of vaccines.

Affiliation Not a UNIGE publication
Citation (ISO format)
BUCKLEY, Paul R et al. Application of modeling approaches to explore vaccine adjuvant mode-of-action. In: Frontiers in Immunology, 2019, vol. 10, p. 2150. doi: 10.3389/fimmu.2019.02150
Main files (1)
Article (Published version)
ISSN of the journal1664-3224

Technical informations

Creation10/12/2020 2:26:00 PM
First validation10/12/2020 2:26:00 PM
Update time03/15/2023 10:46:02 PM
Status update03/15/2023 10:46:00 PM
Last indexation08/30/2023 11:39:56 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack