Mathematical modeling of Ebola virus dynamics as a step towards rational vaccine design

Abstract

The greatest roadblock in vaccine design is the lack of a complete understanding of how the immune system works. Greater understanding can be achieved via mathematical models that formalize biological ideas and their ability to extract non-intuitive information from biological experiments. Rational vaccine design (RVD) aims to maximize the production of pathogen-specific memory cells following vaccination. First, the Herz model for viral dynamics was simulated using MATLAB to analyze the naïve system's response to Ebola - a deadly hemorrhagic virus. The model was initialized for the unvaccinated system using biologically based data on Ebola virus cultivation in Vero cell-cultures. Simulations revealed generally non-quantified specifics of Ebola infection such as the virus' birth, natural death, and cellular infection rates. The second system, initialized with the rates above, modeled Ebola infection in a vaccinated individual using a modified Herz model with equations for memory T-cell formation and proliferation. T-cell populations were expanded under biologically mimicked rates and conditions. These results provide a quantified value for the number of memory T-cells necessary for vaccine efficacy in an individual; the specifications of what the vaccine must accomplish. Reversing the roles, these results may serve as RVD guidelines for biologically effective vaccines against the Ebola virus. © 2010 Springer-Verlag.