Developing VHH-based tools to study Ebolavirus infection

Abstract

Variable domains of camelid-derived heavy chain-only antibodies, or VHHs, have emerged as a unique antigen binding moiety that holds promise in its versatility and utilization as a tool to study biological questions. This thesis focuses on two aspects on developing tools to study infectious disease, specifically Ebolavirus entry. In Chapter 1, I provide an overview about antibodies and how antibodies have transformed the biomedical field and how single domain antibody fragments, or VHHs, have entered this arena. I will also touch upon how VHHs have been used in various fields and certain aspects that remain underexplored. Chapter 2 focuses on the utilization of VHHs to study Ebolavirus entry using VHHs that were isolated from alpacas. Two VHHs were found to neutralize Ebolavirus in both Biosafety Level 2 and 4 laboratory conditions. Ongoing experiments to address mechanism focuses on two aspects of neutralization: Cathepsin inhibition or NPC1-mediated inhibition. Finally, Chapter 3 discusses the overall landscape for Ebolavirus therapeutics and will discuss future directions of this work.