Reservoir population ecology, viral evolution and the risk of emerging infectious disease.

The ecology and life history of wild animals influences their potential to harbour infectious disease. This observation has motivated studies identifying empirical relationships between traits of wild animals and historical patterns of spillover and emergence into humans. Although these studies have identified compelling broad-scale patterns, they are generally agnostic with respect to underlying mechanisms. Here, we develop mathematical models that couple reservoir population ecology with viral epidemiology and evolution to clarify existing verbal arguments and pinpoint the conditions that favour spillover and emergence. Our results support the idea that average lifespan influences the likelihood of an animal serving as a reservoir for human infectious disease. At the same time, however, our results show that the magnitude of this effect is sensitive to the rate of viral mutation. Our results also demonstrate that viral pathogens causing persistent infections or a transient immune response within the reservoir are more likely to fuel emergence. Genetically explicit stochastic simulations enrich these mathematical results by identifying relationships between the genetic basis of transmission and the risk of spillover and emergence. Together, our results clarify the scope of applicability for existing hypotheses and refine our understanding of emergence risk.

Self-disseminating vaccines to suppress zoonoses.

The SARS-CoV-2 epidemic is merely the most recent demonstration that our current approach to emerging zoonotic infectious disease is ineffective. SARS, MERS, Ebola, Nipah and an array of arenavirus infections sporadically spillover into human populations and are often contained only as a result of their poor transmission in human hosts, coupled with intense public health control efforts in the early stages of an emerging epidemic. It is now more apparent than ever that we need a better and more proactive approach. One possibility is to eliminate the threat of spillover before it occurs using vaccines capable of autonomously spreading through wild animal reservoirs. We are now poised to begin developing self-disseminating vaccines targeting a wide range of human pathogens, but important decisions remain about how they can be most effectively designed and used to target pathogens with a high risk of spillover and/or emergence. In this Perspective, we first review the basic epidemiological theory establishing the feasibility and utility of self-disseminating vaccines. We then outline a road map for overcoming remaining technical challenges: identifying high-risk pathogens before they emerge, optimizing vaccine design with an eye to evolution, behaviour and epidemiology, and minimizing the risk of unintended consequences.