A Chip‐Based Surveillance Platform for Detecting Antibody‐Based Immunity and Immune Escape Using SARS‐CoV‐2 Pseudovirus Surrogates

As viral diseases like influenza, COVID-19, and respiratory syncytial virus (RSV) become prevalent, demand for treatments and vaccinations is on the rise. Despite widespread vaccination, concerns remain that emerging virus strains may evade immunity. Monitoring these pathogens is crucial for developing effective treatments, but large-scale population screening, while a public health need, is challenging in terms of speed, efficiency, and cost. Herein we demonstrate the use of a high-throughput, chip-based platform that is scalable to population-wide immune surveillance using SARS-CoV-2 pseudovirus surrogates. We tested antibodies against pseudovirus surrogates bearing the spike protein of the Wuhan-Hu-1 (WT) SARS-CoV-2 on-chip and screened patient-derived sera and eluates from patient-derived and contrived Dried Blood Spots (cDBS) for effectiveness against the WT strain. Interestingly, some sera and cDBS eluates inhibited infection by the Omicron BA.4/5 variant, which emerged a year after sample collection, suggesting cross-reactivity against distinct SARS-CoV-2 spike proteins. This chip-based platform may be used to screen populations for existing immunity and immune escape of emerging viruses and their variants from prior infection and/or vaccination.