Human host response to viral infection: Learning from the live yellow fever vaccine

Abstract

The clinical outcome of acute viral infection is, at least in part, determined by the host response to infection. Conventionally, the approach to defining these host responses is to study patients presenting with acute illness. However, such an approach misses the processes that occur during the pre-symptomatic incubation period. To define the pre-symptomatic events that influence infection and immunity outcomes, we have relied on the commercially available live attenuated yellow fever virus vaccine to simulate acute infection in healthy human volunteers. This vaccine, which is arguably the most potent licensed vaccine in the world - a single dose provides 10 years or more of protection from deadly yellow fever - elicits transient but detectable viremia in ~90% of vaccinees consistently. Moreover, approximately half of the vaccinees would also experience mild, self-limiting, and well-tolerated flu-like symptoms at a median time of 6 days post-vaccination. These features provide us with a safe and reproducible experimental medicine approach to understand how humans respond to viral infections and define the molecular drivers of clinical and immunological outcomes. I will describe the insights we have gleaned from studying this live viral vaccine and how these insights could be applied to treating and preventing acute viral diseases.

Biography

Prof Ooi is a Professor in the Programme in Emerging Infectious Diseases at Duke-NUS Medical School, Singapore. He trained in medicine at the University of Nottingham and then completed his PhD studies at the Department of Microbiology, National University of Singapore. His research interfaces fundamental virology with immunology and experimental medicine studies in order to understand dengue and other flaviviral pathogenesis to shape vaccine and therapeutic development. He co-directs the Viral Research and Experimental Medicine Centre at the SingHealth Duke-NUS Academic Medical Centre (ViREMiCS), which aims to develop molecular endpoints for use in viral disease therapeutic and vaccine trials. He received the Clinician-Scientist (Senior Investigator) Award by the National Medical Research Council of Singapore, in 2010, 2014 and 2019.