This research project investigates the frequency and patterns of zoonotic sarbecovirus (coronavirus subgenus that contains SARS-CoV-2) spillover within high-risk human communities in Myanmar, a recognized hotspot for potential human ACE2-binding coronaviruses. Building on five years of prior surveillance, the study focuses on unique cohorts—including elephant loggers, guano harvesters, and cave pilgrims—who experience frequent contact with bats and pangolins. Preliminary data indicates that individuals in extractive industries are significantly more likely to have been exposed to pre-emergent sarbecoviruses, such as RaTG13, through activities like hunting or slaughtering bats. By establishing longitudinal cohorts and utilizing both archived pre-pandemic specimens and prospective sampling, the project aims to identify specific epidemiological risk factors and evaluate the incidence of household transmission for these viruses.

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To overcome the technical challenges of distinguishing between closely related viruses, the project utilizes a novel multiplex surrogate virus neutralization assay (sVNT) developed by our colleagues at Duke-NUS. This powerful serology platform can simultaneously detect neutralizing antibodies (NAbs) against 21 different sarbecoviruses, including SARS-CoV-2 variants and various pre-emergent bat and pangolin coronaviruses. The research seeks to determine how natural exposure to a diverse range of zoonotic sarbecoviruses influences the development of broadly reactive "pan-sarbecovirus" immunity. A key working hypothesis is that cross-antigenic clade exposure—occurring before natural SARS-CoV-2 infection or vaccination—may induce a more robust and broader neutralizing antibody response capable of covering future variants of concern.

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In addition to immunological analysis, the project employs a community-based participatory approach to investigate the behavioral drivers of zoonotic transmission. Through qualitative focus groups and quantitative surveys, researchers document socio-cultural norms, economic incentives, and practices related to bushmeat hunting and traditional medicine. This integrated approach aims to characterize the human-wildlife interface in remote regions and identify culturally appropriate mitigation strategies to prevent future spillover events. Ultimately, the findings will inform global vaccine development strategies by providing insight into the most effective cross-clade immunization patterns for achieving broad-spectrum protection against coronaviruses with pandemic potential.

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This work is supported by the National Institute of Allergy and Infectious Diseases.

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