Development and assessment of novel, high-throughput immunological assays to improve surveillance of spillover of viral families of pandemic potential

Context Emerging infections pose a significant burden on healthcare systems and result in economic loss for societies worldwide as exemplified by the COVID-19 pandemic. Another new viral pathogen, causing ‘disease X’, will likely emerge in the future and pandemic preparedness is thus one of the top priorities of global agencies (UN, WHO, G20) and national governments. Vulnerable health systems, dense populations with close human-animal interactions, rapid urbanization and economic development, and stark health inequalities render Southeast Asia a hotspot for outbreaks of new and existing infectious pathogens, in particular zoonotic viruses. Yet, the region represents a weakness in pandemic preparedness and response. The challenge the project addresses Early detection of spillover events is critical to informing coordinated global responses, including the rapid development and deployment of effective and safe countermeasures, (especially diagnostics, therapeutics and vaccines) to prevent future pandemics or mitigate their health and societal impact. Existing surveillance platforms are primarily based on clinical diagnosis in healthcare settings supplemented, in some areas, by genomic surveillance. They often therefore fail to capture early cases and those with asymptomatic or mild infection. Despite their potential utility, owing to the current low throughput and technical challenges, antibody and T-cell assays are rarely used for zoonotic spillover detection. Here, we will first develop high-throughput, high-resolution antibody and T-cell assays to enable early detection of spillover events. We will then apply the developed assays to comprehensively map out the immune landscape against zoonotic viruses of the families Coronaviridae, Orthomyxoviridae and Paramyxoviridae in high-risk populations in Cambodia and Vietnam. The data will be used to evaluate how immunological data could be utilised as part of broader surveillance strategies and estimate their potential to improve earlier detection of spillover events. Finally, potent, broadly neutralizing antibodies against zoonotic viruses will be discovered using samples collected from study participants with a confirmed infection. Aims and objectives Our aims are To develop novel, high-throughput immunological tools for viral families of epidemic/pandemic potential To apply the assays developed under Aim 1 to map out the immune landscape against zoonotic viruses with pandemic potential in high-risk populations in Cambodia and Vietnam To utilize the data from Aims 1 and 2 to evaluate the utility of the novel immunological tools as part of broader surveillance strategies and estimate their potential to improve earlier detection of spillover events To discover potent and broadly neutralising antibodies against zoonotic viruses causing spillover documented under Aim 2 Potential applications and benefits Our project will ultimately build regional research capacity in immunology, metagenomics, modeling and monoclonal antibody discovery in Cambodia and Vietnam. Importantly, a strong collaborative network across the region, linked with international experts in the UK and Singapore will be established. Therefore, our collective outputs would lay the foundation for locally-led responses to future emerging infections.