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Dynamic Monitoring of Seroconversion using a Multianalyte Immunobead Assay for Covid-19
Published on: February 16, 2022
SARS-CoV-2 immune repertoire in MIS-C and pediatric COVID-19
Supriya Ravichandran1, Juanjie Tang1, Gabrielle Grubbs1
1Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA.
Insights
Researchers identified unique severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody signatures in children. These viral fingerprints correlate with disease severity and offer targets for diagnostics and vaccines.
Area of Science:
- Virology
- Immunology
- Pediatrics
Background:
- Understanding the antibody response to SARS-CoV-2 in children is limited.
- Pediatric COVID-19 presents with diverse clinical manifestations, including multisystem inflammatory syndrome in children (MIS-C).
Purpose of the Study:
- To characterize the viral antibody fingerprint in children following SARS-CoV-2 infection.
- To identify antibody signatures associated with disease severity and potential serodiagnostic targets.
Main Methods:
- Proteome-wide immunoprofiling of children with varying COVID-19 severity, MIS-C, and controls.
- Analysis of IgM, IgG, and IgA epitope diversity, antibody binding, and avidity.
- Assessment of antibody-binding kinetics and neutralization capacity.
Main Results:
- Antibodies recognized epitopes beyond spike and nucleocapsid proteins, including nonstructural proteins (NSPs) and open reading frames (ORFs).
- Specific antibody parameters distinguished between mild/moderate COVID-19, severe COVID-19, and MIS-C.
- Antibody avidity to the prefusion spike protein correlated with decreased illness severity.
Conclusions:
- SARS-CoV-2 infection induces distinct antibody signatures in children, varying with disease severity.
- Identified epitopes in NSP12, ORF3a, and ORF8 show potential for serodiagnosis.
- Antibody responses, particularly neutralization, highlight targets for vaccine and therapeutic development in pediatric populations.
Abstract:
There is limited understanding of the viral antibody fingerprint following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children. Herein, SARS-CoV-2 proteome-wide immunoprofiling of children with mild/moderate or severe coronavirus disease 2019 (COVID-19) versus multisystem inflammatory syndrome in children versus hospitalized control patients revealed differential cytokine responses, IgM/IgG/IgA epitope diversity, antibody binding and avidity. Apart from spike and nucleocapsid, IgG/IgA recognized epitopes in nonstructural protein (NSP) 2, NSP3, NSP12-NSP14 and open reading frame (ORF) 3a-ORF9. Peptides representing epitopes in NSP12, ORF3a and ORF8 demonstrated SARS-CoV-2 serodiagnosis. Antibody-binding kinetics with 24 SARS-CoV-2 proteins revealed antibody parameters that distinguish children with mild/moderate versus severe COVID-19 or multisystem inflammatory syndrome in children. Antibody avidity to prefusion spike correlated with decreased illness severity and served as a clinical disease indicator. The fusion peptide and heptad repeat 2 region induced SARS-CoV-2-neutralizing antibodies in rabbits. Thus, we identified SARS-CoV-2 antibody signatures in children associated with disease severity and delineate promising serodiagnostic and virus neutralization targets. These findings might guide the design of serodiagnostic assays, prognostic algorithms, therapeutics and vaccines in this important but understudied population.
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