Modeling the impact of inoculum dose on within-host virus dynamics, immune response, and disease

Abstract

Inoculum dose, i.e. the number of pathogens at the beginning of an infection, is an important determinant of infection outcomes. Inoculum dose can affect key aspects of viral dynamics following an infection, and viral dynamics in turn can affect the ensuing immune responses. Viral dynamics and immune response together determine clinically relevant outcomes, such as morbidity and mortality. In this dissertation, at first the impact of inoculum dose on the key aspects of viral dynamics, immune responses, and diseases is addressed by investigating several previously published experimental results of acute virus infections. Inoculum dose-dependent patterns of virus dynamics are well characterized, and systematically studied through mathematical modeling. Additionally, an important biological immune response mechanism determining inoculum dose-dependent virus dynamics is further illustrated and tested statistically. Finally, several novel mathematical models are employed to a pathogenesis study of a specific virus strain infection, and an intermediate inoculum dose which induces optimal immunity while minimizing side effects is postulated, this might be very beneficial information in the development of vaccine design.