Humoral Immune Response Profile of COVID-19 Reveals Severity and Variant-Specific Epitopes: Lessons from SARS-CoV-2 Peptide Microarray

Abstract

The amaranthine scale of the COVID-19 pandemic and unpredictable disease severity is of grave concern. Serological diagnostic aids are an excellent choice for clinicians for rapid and easy prognosis of the disease. To this end, we studied the humoral immune response to SARS-CoV-2 infection to map immunogenic regions in the SARS-CoV-2 proteome at amino acid resolution using a high-density SARS-CoV-2 proteome peptide microarray. The microarray has 4932 overlapping peptides printed in duplicates spanning the entire SARS-CoV-2 proteome. We found 204 and 676 immunogenic peptides against IgA and IgG, corresponding to 137 and 412 IgA and IgG epitopes, respectively. Of these, 6 and 307 epitopes could discriminate between disease severity. The emergence of variants has added to the complexity of the disease. Using the mutation panel available, we could detect 5 and 10 immunogenic peptides against IgA and IgG with mutations belonging to SAR-CoV-2 variants. The study revealed severity-based epitopes that could be presented as potential prognostic serological markers. Further, the mutant epitope immunogenicity could indicate the putative use of these markers for diagnosing variants responsible for the infection.

Humoral Immune Response to SARS-CoV-2 Spike Protein Receptor-Binding Motif Linear Epitopes

“…Similarly, other works analyzing B-cell epitopes observed that RBM sequences (NGVEGFNCYFP) are less serologically reactive than other S1 and S2 regions [REF-A novel precision-serology assay for SARS-CoV-2 infection based on linear B-cell epitopes of Spike protein]. Analogously to our study, a peptide array revealed that highly immunogenic regions belong to regions outside the RBD [40].…”

Mapping IgA Epitope and Cross-Reactivity between Severe Acute Respiratory Syndrome-Associated Coronavirus 2 and DENV

“…While some prior studies have identified IgA epitopes of the spike protein from SARS-CoV-2 [ 23 , 29 , 31 ], this is the first study to provide a comprehensive list of the IgA epitome. Out of the total epitopes identified, most (32) exhibited cross-reactivity with proteins from DENV and other organisms, including coronaviruses.…”

“…Several other investigators have also examined various aspects of the IgA immune response to the S protein in the context of COVID-19. They have utilized various techniques, such as studying fragments of peptides with different sizes [ 29 ], exploring antibody affinity maturation in relation to clinical outcomes in hospitalized COVID-19 patients [ 30 ], employing microarray analysis of peptides to investigate the disease severity over time in a small cohort of patients [ 23 ], and using a microarray of peptides technology to analyze the humoral response profile to COVID-19 [ 31 ].…”

ASFV epitope mapping by high density peptides microarrays

“…This could not only contribute to the optimization of diagnostic and prognostic methods, but also for breaking ground for developing new vaccine strategies. To this end, peptide microarray-based technologies are valuable tools to study host-pathogen interactions at biomolecular level due to their potential for epitope detection at the amino acid resolution ( Acharjee et al., 2023 ).…”