Antibody Mediated Immunity to SARS-CoV-2 and Human Coronaviruses: Multiplex Beads Assay and Volumetric Absorptive Microsampling to Generate Immune Repertoire Cartography

• Published in: Frontiers in immunology Vol. 12; p. 696370
• Main Authors: Wang, Jiong, Li, Dongmei, Zhou, Qian, Wiltse, Alexander, Zand, Martin S.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 27.07.2021
• Subjects: anti-S and anti-N antibodies; Antibodies, Viral - blood; Antibodies, Viral - immunology; Betacoronavirus - immunology; Coronavirus - immunology; Coronavirus 229E, Human - immunology; Coronavirus NL63, Human - immunology; Coronavirus Nucleocapsid Proteins - immunology; Coronavirus OC43, Human - immunology; COVID-19 - immunology; Cross Reactions - immunology; human coronaviruses (HCoVs); Humans; Immunoassay - methods; Immunoglobulin A - blood; Immunoglobulin A - immunology; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulin M - blood; Immunoglobulin M - immunology; Immunology; mPlex-CoV assay; preexisting human coronavirus immunity; SARS-CoV-2; SARS-CoV-2 - immunology; Severe acute respiratory syndrome-related coronavirus - immunology; Spike Glycoprotein, Coronavirus - immunology; volumetric absorptive micro-sampling (VAMS); SARS-CoV-2; human coronaviruses (HCoVs); mPlex-CoV assay; volumetric absorptive micro-sampling (VAMS); cross-reactive antibody immunity; preexisting human coronavirus immunity; COVID-19 vaccine studies; anti-S and anti-N antibodies
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.696370

The COVID-19 pandemic is caused by SARS-CoV-2, a novel zoonotic coronavirus. Emerging evidence indicates that preexisting humoral immunity against other seasonal human coronaviruses (HCoVs) plays a critical role in the specific antibody response to SARS-CoV-2. However, current work to assess the effects of preexisting and cross-reactive anti-HCoVs antibodies has been limited. To address this issue, we have adapted our previously reported multiplex assay to simultaneously and quantitatively measure anti-HCoV antibodies. The full mPlex-CoV panel covers the spike (S) and nucleocapsid (N) proteins of three highly pathogenic HCoVs (SARS-CoV-1, SARS-CoV-2, MERS) and four human seasonal strains (OC43, HKU1, NL63, 229E). Combining this assay with volumetric absorptive microsampling (VAMS), we measured the anti-HCoV IgG, IgA, and IgM antibodies in fingerstick blood samples. The results demonstrate that the mPlex-CoV assay has high specificity and sensitivity. It can detect strain-specific anti-HCoV antibodies down to 0.1 ng/ml with 4 log assay range and with low intra- and inter-assay coefficients of variation (%CV). We also estimate multiple strain HCoVs IgG, IgA and IgM concentration in VAMS samples in three categories of subjects: pre-COVID-19 (n=21), post-COVID-19 convalescents (n=19), and COVID-19 vaccine recipients (n=14). Using metric multidimensional scaling (MDS) analysis, HCoVs IgG concentrations in fingerstick blood samples were well separated between the pre-COVID-19, post-COVID-19 convalescents, and COVID-19 vaccine recipients. In addition, we demonstrate how multi-dimensional scaling analysis can be used to visualize IgG mediated antibody immunity against multiple human coronaviruses. We conclude that the combination of VAMS and the mPlex-Cov assay is well suited to performing remote study sample collection under pandemic conditions to monitor HCoVs antibody responses in population studies.