Modeling the dependence of immunodominance on T Cell dynamics in prime-boost vaccines

Abstract

The protection induced by vaccines against infectious diseases such as malaria, dengue or hepatitis relies on a the creation of immune memory by T cells, key components of the human immune system. The induction of a strong T cell response leading to long lasting memory can be improved by using prime-boost (PB) vaccines, which consist in successive inoculations of appropriate vectors carrying target antigens that can be recognized by specific T cell clones. A problem faced by PB vaccines is the fact that T cell response is often biased towards a few clones that can identify only a small set of antigens, out of the many that could be displayed by the pathogen. This phenomenon, known as immunodominance, can significantly compromise the effectiveness of vaccination. In this work we will use mathematical modeling to better understand the role of T cell population dynamics in the onset of immunodominance in PB vaccines. In particular, we will use mathematical analysis and simulations to compare single-dose vaccines with PB ones, both for homologous (where the same antigen is used in every shot) and heterologous protocols (in which different antigens are used at each step).