Evaluating Spike Antigenicity across Endemic Human Coronavirus Models using Flow Virometry
Burnie, J.; Ouano, C.; Luo, V.; Dzuvor, C. K. O.; Miller, T.; Ospina, G.; Tanneti, N. S.; Tan, L. H.; Hamel, D. J.; Hammond, C.; Matthews, H.; Evanson, L. R.; Joseph, J.; Moak, S. P.; Kanki, P.; Cohen, N. A.; Weiss, S. R.; Corbett-Helaire, K. S.
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While SARS-CoV-2 research has advanced rapidly since COVID-19, endemic human coronaviruses (HCoVs) remain comparatively understudied. Tools to phenotype spike (S), the primary antigenic target on coronaviruses, at the single-virion level could improve vaccine design by capturing variation in epitope availability and spike abundance. Here, we establish a calibrated flow virometry (FV) platform to quantify S antigenicity on native endemic (HCoV-229E, HCoV-OC43) and epidemic (SARS-CoV-2) coronaviruses directly in cell culture supernatants. FV revealed cell line-dependent differences in S antigenicity, including receptor-induced changes in epitope accessibility. Comparison of virion-associated S with recombinant stabilized S by ELISA and biolayer interferometry showed consistent binding for HCoV-OC43, MERS-CoV, and SARS-CoV-2, but differences for HCoV-229E, with FV resolving heterogeneity not captured by bulk assays. Finally, FV showed that HCoV-229E from patient-derived air-liquid interface cultures exhibited reduced antibody binding and distinct S antigenicity compared to cell line-derived virions. Together, these findings establish FV as a platform for single-virion analysis of HCoV antigenicity.
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