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Vaccine Ampoules. Photo credit to Max Pixel

Vaccine IS/ID Modelling Consortium

Using model-based drug development methods (PK/PD) to accelerate vaccine dose decision making.

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About IS/ID Modelling

The vaccine IS/ID consortium aim to compliment the existing dose-finding methods used in vaccine development with mathematical frameworks translated from drug development.

IS/ID Discussion Forum

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About IS/ID Modelling
About ISID

The vaccine IS/ID modelling consortium are vaccine developers, drug developers, mathematical modellers and regulators interested in using mathematical modelling methods to improve decisions around vaccine dose development. 

Vaccine dosing decision making employs relatively antiquated methods compared to the methods employed for drug dosing decision making. The vaccine IS/ID consortium aim to compliment the existing dose-finding methods used in vaccine development with mathematical frameworks translated from drug development. As such, we propose the new field of vaccine immunostimulation/immunodynamic modelling.

Our aims

  • Quantification of vaccine dose response curves

  • Utilization of optimal design methods to design vaccine trials with the least possible resources

  • Translation of dose response curves across species

  • Vaccination regimen design

  • Vaccine trial simulation

Members
Profiles
Profiles List
Consortium Members
Prof Richard White

Richard
White

Prof of Infectious Disease Modelling
LSHTM
Tom Evans

Thomas Evans

CEO / VACCITECH
LSHTM
LSHTM
LSHTM
Steve Kern

Steve Kern

Deputy Director, Quantitative Sciences / BMGF
Research
Research ISID

IS/ID modelling is currently being implemented in the following areas

Tuberculosis

First steps to include IS/ID modelling into vaccine development are under way in TB research.

We designed and conducted an intensive animal vaccine multi-dose study of a candidate TB vaccine (presently in phase 2)  specifically to generate data to translate dose response curves to humans.

The predicted best TB vaccine dose is likely to be lower than previously investigated

(data published here)

A T cell mathematical model predicts dose-dependent difference in mouse immune response following vaccination

(Data presented at the 2017 Union World Conference on Lung Health. Abstract no. SOA-328-12, pg. S85)

 

Adenovirus

Vaccitech and the ISID consortium have undertaken a study to understand the nature of the dose-related T cell responses following a single dose of replication incompetent adenoviral vaccines. A systematic review that is registered in Prospero is underway, and the extracted data will then be analysed to try an generate the most likely response dose profile. We will apply this data to an adaptive design of the next Vaccitech product to enter Phase 1 human trials, in order to arrive at the best decision on dose selection, with knowledge of the confidence interval surrounding that decision.

Publications
Resources
Publications
Publications List
Using Data from Macaques To Predict Gamma Interferon Responses after Mycobacterium bovis BCG Vaccination in Humans: a Proof-of-Concept Study of Immunostimulation/Immunodynamic Modeling Methods
Rhodes SJ, Sarfas C, Knight GM, White A, Pathan AA, McShane H, Evans TG, Fletcher H, Sharpe S, White RG.
2017
10.1128/CVI.00525-16
The TB vaccine H56+IC31 dose-response curve is peaked not saturating: Data generation for new mathematical modelling methods to inform vaccine dose decisions
Rhodes SJ, Zelmer A, Knight GM, Prabowo SA, Stockdale L, Evans TG, Lindenstrøm T, White RG, Fletcher H.
2016
10.1016/j.vaccine.2016.10.060
Individual-level factors associated with variation in mycobacterial-specific immune response: Gender and previous BCG vaccination status
Rhodes SJ, Knight GM, Fielding K, Scriba TJ, Pathan AA, McShane H, Fletcher H, White RG.
2016
10.1016/j.tube.2015.10.002
Discussion Forum
Discussion Forum Intro

We would like to encourage a discussion on the use of IS/ID modelling to improve vaccine dose finding. We welcome any questions or comments. Please send your comment by clicking on the button below.

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