A mathematical study of adaptive immune responses following exposure to Ebola virus disease

Ebola virus (EBOV) is now one of the most feared pathogens worldwide, as recently demonstrated in the West African Ebola outbreak: between December 2013 and April 2016, the largest epidemic of Ebola virus disease (EVD) to date generated more than 28,000 cases and more than 11,000 deaths in the populations of Guinea, Liberia, and Sierra Leone. In some patients, antigen-specific (or adaptive) immune responses develop in time to restrict viral replication and leading to survival of the individual, otherwise death occurs one to two weeks after the onset of symptoms. No anti-viral drug has been identified to block ebolavirus replication.

This project is based on the hypothesis (supported by murine infection models, as well as rhesus macaque models) that an specific adaptive immune response in lethal EBOV infection can be protective upon transfer to naive EBOV infected recipients. That is, that the timing and characteristics of the specific adaptive immune response initiated in an EBOV infected individual are predictors of survival or death. The aim of the project, in collaboration with Publich Health England (PHE), is to develop mathematical models of adaptive immune responses following exposure to Ebola virus disease. The mathematical models, together with clinical data, provided by Professor Miles Carroll (PHE), of innate and adaptive immune responses to EBOV, as well as with Bayesian methods, will allow us to characterise and quantify the temporal dynamics of host adaptive cells during an infection, and in doing so, identify the differences in host adaptive immune responses that lead to survival or death.