1. Antigen-based multiplex strategies to discriminate SARS-CoV-2 natural and vaccine induced immunity from seasonal human coronavirus humoral responses
- Author
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Spencer L. Sterling, Lanteri C, Emily C Samuels, Eugene V. Millar, Burgess Th, Mark P Simons, de Wit E, Nusrat J. Epsi, Dominic Esposito, Munster, Katrin Mende, Edward Mitre, Si'Ana A Coggins, Clifton Gt, Shreshta Phogat, Kevin K. Chung, Lianying Yan, Eric D Laing, Christian L. Coles, Christopher C. Broder, David R. Tribble, Nicole Moreno, Matthew Drew, Simon Pollett, Stephanie A Richard, Merritt S, and Jennifer Mehalko
- Subjects
Innate immune system ,medicine.diagnostic_test ,viruses ,fungi ,Protein domain ,virus diseases ,Biology ,Virology ,Article ,body regions ,Vaccination ,Antigen ,Immunity ,Immunoassay ,biology.protein ,medicine ,Multiplex ,Antibody ,skin and connective tissue diseases - Abstract
Sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 sero-surveillance. With the rollout of SARS-CoV-2 vaccines, such assays must be able to distinguish vaccine from natural immunity to SARS-CoV-2 and related human coronaviruses. Here, we developed and implemented multiplex microsphere-based immunoassay strategies for COVD-19 antibody studies that incorporates spike protein trimers of SARS-CoV-2 and the endemic seasonal human coronaviruses (HCoV), enabling high throughout measurement of pre-existing cross-reactive antibodies. We varied SARS-CoV-2 antigen compositions within the multiplex assay, allowing direct comparisons of the effects of spike protein, receptor-binding domain protein (RBD) and nucleocapsid protein (NP) based SARS-CoV-2 antibody detection. Multiplex immunoassay performance characteristics are antigen-dependent, and sensitivities and specificities range 92-99% and 94-100%, respectively, for human subject samples collected as early as 7-10 days from symptom onset. SARS-CoV-2 spike and RBD had a strong correlative relationship for the detection of IgG. Correlation between detectable IgG reactive with spike and NP also had strong relationship, however, several PCR-positive and spike IgG-positive serum samples were NP IgG-negative. This spike and NP multiplex immunoassay has the potential to be useful for differentiation between vaccination and natural infection induced antibody responses. We also assessed the induction ofde novoSARS-CoV-2 IgG cross reactions with SARS-CoV and MERS-CoV spike proteins. Furthermore, multiplex immunoassays that incorporate spike proteins of SARS-CoV-2 and HCoVs will permit investigations into the influence of HCoV antibodies on COVID-19 clinical outcomes and SARS-CoV-2 antibody durability.
- Published
- 2021