Vaccines and Viral Infections Impact Immune Landscaping for Future Immune Challenges

Abstract

Human immunity does not occur in a vacuum. In contrast to some of the animals used in preclinical models, humans have a lifetime history of vaccinations and infections. These immunogenic exposures imprint on the immune system and for most, provide substantial memory responses that mitigate disease severity upon re-exposure. However, in some cases these preexisting immunological responses change how a person responds to new antigens, which can either be beneficial or detrimental. In this dissertation we aim to explore four instances in which preexisting immune responses impact subsequent immunity. I will discuss the role of conjugate vaccination in leveraging preexisting T cell responses to drive antibody production to unrelated antigens (Chapter 2). Next, I will discuss the impact of antibodies on phagocytes using an in vitro model for passive immunization (Chapter 3). The impact of chronic infection on subsequent acquired immunity will be discussed in the context of HIV (Chapter 4) and CMV (Chapter 5) for their ability to influence T cell immunity in the setting of HCV (Chapter 4) and transplant (Chapter 5), respectively. This collection of studies provided me with the opportunity to determine that the functionality of immune cells is altered by these previous antigen exposures in ways that might explain clinical outcomes. We concluded that immune history meaningfully alters immune responses, and it is important to consider while investigating human immunopathology and for developing therapies for human disease.