Quiescence to emergence: Does nairovirus diversity loss increase disease transmission, severity and the risk of emergence?

Disease emergence occurs when a pathogen spills over into and spreads in a novel host population, or when established host-pathogen interactions change, leading to an increase in the incidence and / or severity of disease. The role of biodiversity in disease emergence has been investigated primarily from two angles: First, emergence risk may be exacerbated in areas where host populations of interest about biodiversity hotspots, since these are likely to contain a multitude of candidate pathogens -- some poised for emergence. On the other hand, host diversity may dilute emergence risk for some generalist pathogens, because the most competent hosts tend to be less abundant in diverse ecological communities. As such, in the context of disease emergence, pathogen biodiversity is typically thought to pose a threat, whereas host biodiversity is often considered to offer protection. Since host and pathogen biodiversity are tightly linked, the consequences of biodiversity loss for disease emergence are thus difficult to predict. Here we offer a novel perspective on the links between biodiversity loss and disease emergence: We hypothesize that the loss of pathogen biodiversity may contribute to disease emergence risk, because it reduces the richness of (mild / subclinical) infections by pathogens that are related to, but distinct from the dangerous infectious agents that are most likely to cause disease emergence. Specifically, we posit that exposure to diverse related pathogens prompts hosts to establish multivalent cross-reactive antibody portfolios, which can (i) prevent severe disease, (ii) reduce transmission, and ultimately (iii) limit the risk of emergence of potentially harmful pathogens into ecological niches that they could occupy. If true, these insights could be applied to (iv) design multivalent "portfolio" vaccines, which can provide relatively stable protection against broad viral lineages. We propose to investigate these ideas using East African nairoviruses as a model system, which include important animal (e.g. Nairobi Sheep Disease Virus, NSDV) and zoonotic (e.g. Crimean-Congo Haemorrhagic Fever Virus, CCHFV) pathogens, as well as species not known to cause disease in either host (e.g. Dugbe virus, Macira virus). Conceptually, the plausibility of our hypothesis is supported by examples of human disease emergence (e.g. influenza, monkeypox) driven by a population-level decline in natural or vaccine-induced pathogen exposure. With this study, we hope to contribute significantly in two connected areas of investigation. First, we re-cast competitive exclusion and community invasibility, familiar concepts in community ecology, in the context of co-circulating related pathogens. Immuno-epidemiological models are pivotal here, because they link mechanisms that occur within individual hosts (i.e., cross-immunity among related pathogens) with consequences that play out in host, vector and pathogen communities. As such, the proposed work establishes a versatile, data-driven multi-scale modeling platform to understand how the diversity of related pathogens mediates disease emergence risk. Second, we leverage this new perspective on emergence risk to pioneer a novel approach to vaccine design. Conventionally, vaccines are tightly targeted to prevent infection by well characterized pathogens: a powerful approach, albeit with limitations in the face of novel pathogen threats. Our work evaluates the idea that broadly targeted "portfolio" vaccines could reduce the risk and possible impacts of disease emergence - potentially shifting the role of vaccines in pandemic preparedness from response to prevention.