Serum IgG anti-SARS-CoV-2 Binding Antibody Level Is Strongly Associated With IgA and Functional Antibody Levels in Adults Infected With SARS-CoV-2
| Autor: | Xunyan Ye, Laura S. Angelo, Erin G. Nicholson, Obinna P. Iwuchukwu, Wanderson Cabral de Rezende, Anubama Rajan, Letisha O. Aideyan, Trevor J. McBride, Nanette Bond, Patricia Santarcangelo, Yolanda J. Rayford, Laura Ferlic-Stark, Sonia Fragoso, Zoha Momin, Hongbing Liu, Khanghy Truong, Brianna Lopez, Margaret E. Conner, Andrew P. Rice, Jason T. Kimata, Vasanthi Avadhanula, Pedro A. Piedra |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
binding antibody Immunology serology medicine.disease_cause Antibodies Viral Serology COVID-19 Serological Testing Blocking antibody medicine Seroprevalence Humans Immunology and Allergy Receptor Neutralizing antibody Coronavirus Original Research biology business.industry SARS-CoV-2 COVID-19 RC581-607 human serum functional antibody Immunoglobulin A Titer HEK293 Cells Immunoglobulin G biology.protein Female Antibody Immunologic diseases. Allergy business |
| Zdroj: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2021.693462/full |
| Popis: | BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 in Wuhan, China, and then rapidly spread causing an unprecedented pandemic. A robust serological assay is needed to evaluate vaccine candidates and better understand the epidemiology of coronavirus disease (COVID-19).MethodsWe used the full-length spike (S) protein of SARS-CoV-2 for the development of qualitative and quantitative IgG and IgA anti-S enzyme linked immunosorbent assays (ELISA). A total of 320 sera used for assay development were comprised of pandemic sera from SARS-CoV-2 infected adults (n=51) and pre-pandemic sera (n=269) including sera from endemic human coronavirus infected adults. Reverse cumulative curves and diagnostic test statistics were evaluated to define the optimal serum dilution and OD cutoff value for IgG anti-S and IgA anti-S ELISAs. The IgG and IgA anti-S, and three functional antibodies (ACE-2 receptor blocking antibody, lentipseudovirus-S neutralizing antibody, and SARS-CoV-2 neutralizing antibody) were measured using additional SARS-CoV-2 PCR positive sera (n=76) and surveillance sera (n=25). Lastly, the IgG and IgA anti-S levels were compared in different demographic groups.ResultsThe optimal serum dilution for the qualitative IgG anti-S ELISA was at 1:1024 yielding a 99.6% specificity, 92.2% sensitivity, 92.9% positive predictive value (PPV), and 99.6% negative predictive value (NPV) at a SARS-CoV-2 seroprevalence of 5%. The optimal serum dilution for the qualitative IgA anti-S ELISA was at 1:128 yielding a 98.9% specificity, 76.5% sensitivity, 78.3% PPV, and 98.8% NPV at the same seroprevalence. Significant correlations were demonstrated between the IgG and IgA (r=0.833 for concentrations, r=0.840 for titers) as well as between IgG and three functional antibodies (r=0.811-0.924 for concentrations, r=0.795-0.917 for titers). The IgG and IgA anti-S levels were significantly higher in males than females (pConclusionWe developed a highly specific and sensitive IgG anti-S ELISA assay to SARS-CoV-2 using full length S protein. The IgG anti-S antibody level was strongly associated with IgA and functional antibody levels in adults with SARS-CoV-2 infection. Gender and disease severity, rather than age, play an important role in antibody levels. |
| Databáze: | OpenAIRE |
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