This project will be based at the London School of Hygiene and Tropical medicine and partnered with Vaccitech, an Oxford-based vaccine developers.

Vaccines, once developed, are one of the cheapest ways of saving human lives. But, developing a new vaccine can take decades, and cost around a billion dollars. The current scientific methods used to identify the right amount of vaccine dose are empirical and antiquated. In contrast, mathematical model-based drug development (PK/PD) is regularly used to predict the best size and schedule of dose to use. We are translating the modelling techniques used for drug development, to vaccine development, and launching a new scientific field - immunostimulation/ immunodynamic (IS/ID) modelling.

You will build on our previous dose-response mathematical modelling work, to focus on adenoviral constructs and Modified vaccinia Ankara, two viral vectors which are often used in combination to induce T cells responses. A “prime-boost combination” has been widely used in animals and humans, including in advanced studies of tuberculosis, HIV, Ebola, RSV, HCV, and even prostate cancer. However, minimal work has been carried out to understand the best doses of vaccines when used in combination.

The candidate will aim to complete the following tasks. First, using existing experimental data, a novel statistical/mechanistic model will be created and parameterised to make predictions for the adenoviral vaccine dose/immunological response relationship in mice. Second, these predictions will be improved, by simulating mouse responses in an experimental design that maximises the dose-response information gained, and minimising the number of mice used. This will then be validated by empirical mouse studies by project partners, Vaccitech. Third, using an allometric scaling assumption and statistical/mechanistic modelling, initial predictions for the most immunogenic dose-response relationship in humans, will be made based on the mouse data. These predictions will be evaluated in new empirical clinical trials carried out at Vaccitech.

In additional to the creation of new knowledge, the project has a route to impact on vaccine development policy, and wider economic and societal impact.