Cross-Reactivity of SARS-CoV Structural Protein Antibodies Against SARS-CoV-2

In the ongoing COVID-19 pandemic, there remain essential unanswered questions regarding the nature and significance of the humoral immune response towards other coronavirus infections. In this study, we investigate the cross-reactivity of antibodies raised against the first SARS-CoV for their reactivity towards the novel SARS-CoV-2. We extensively characterize a selection of 10 antibodies covering all of the SARS-CoV structural proteins: Spike, Membrane, Nucleocapsid, and Envelope. We determine the reactivity of these antibodies to SARS-CoV-2 in several assays including immunofluorescence of live SARS-CoV-2 infected cells, binding kinetics by biolayer interferometry, ELISA, western blotting, and neutralization. Remarkably, nearly all of the examined SARS-CoV antibodies displayed some level reactivity to SARS-CoV-2, indicating a potentially generalizable theme of cross-reactivity between coronavirus infections across all four structural proteins. The implications of our work are two-fold. Firstly, we have established a set of antibodies with known reactivity to both SARS-CoV and SARS-CoV-2, which will allow further study of both viruses. Secondly, we provide empirical evidence of the high propensity for antibody cross-reactivity between distinct strains of human coronaviruses. This information will be critical to the development of diagnostic tools, and for vaccine development efforts. Funding: This work was supported by NIH training grant T32AI747225 on Interactions at the Microbe-Host Interface and OHSU Innovative IDEA grant 1018784. BLI data was generated on an Octet Red 384, which is made available and supported by the OHSU Proteomics Shared Resource facility and equipment grant number S10OD023413. We acknowledge the support of the members of the Messer lab who performed collection of patient samples, and the patients who agreed to donate samples for scientific research.