UCLA

Recent control efforts for Ebola Virus Disease (EVD) outbreaks in the Democratic Republic of Congo (DRC) employed a highly effective recombinant vesicular stomatitis virus-Zaire Ebola vaccine (rVSVΔG-ZEBOV-GP). Given the previously limited opportunities to study EVD vaccination in real-world outbreaks, little is known about this new vaccine in practice beyond its notable efficacy and safety. This dissertation aims to expand our knowledge of EVD vaccination to better understand the new landscape of EVD outbreaks which now includes effective vaccination and treatment. This dissertation focuses on studying the effects of EVD exposure history (being exposed to a family member with EVD, a close contact with EVD, a contact of a contact with EVD, or being potentially exposed to a patient with EVD in a healthcare setting) on post-vaccination transmission behaviors and vaccine immunogenicity. Additionally, this dissertation looks at how vaccination impacts occupational transmission risk among healthcare workers affected by EVD outbreaks in the DRC. Chapter 1 is a brief introduction to Ebola virus, EVD, and Ebola vaccination with a focus on the DRC. Chapter 2 uses longitudinal data from a vaccinated Congolese cohort to show that healthcare workers have unique post-vaccination risk behavior profiles. Chapter 3 uses another Congolese cohort to show that there are few longitudinal differences between vaccinated and unvaccinated healthcare workers, with the exception that vaccinated individuals are more likely to participate in funeral rites during a period containing a resurgent outbreak. Chapter 4 uses g-computation to assess the causal structure underlying EVD exposure history, baseline antibody titer, and vaccine immunogenicity. This chapter shows that while healthcare workers have lower titers at 21 days post vaccination, this does not seem to be mediated by baseline antibody titer. However, an increased baseline titer led to a more robust immune response to vaccination, regardless of EVD exposure history. Finally, Chapter 5 discusses in detail the overall strengths, limitations, and conclusions from this dissertation.