ORCID Profile
0000-0002-8210-6559
Current Organisation
Sengenics Corporation
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Publisher: MDPI AG
Date: 28-04-2021
DOI: 10.3390/V13050786
Abstract: The COVID-19 pandemic has affected all in iduals across the globe in some way. Despite large numbers of reported seroprevalence studies, there remains a limited understanding of how the magnitude and epitope utilization of the humoral immune response to SARS-CoV-2 viral anti-gens varies within populations following natural infection. Here, we designed a quantitative, multi-epitope protein microarray comprising various nucleocapsid protein structural motifs, including two structural domains and three intrinsically disordered regions. Quantitative data from the microarray provided complete differentiation between cases and pre-pandemic controls (100% sensitivity and specificity) in a case-control cohort (n = 100). We then assessed the influence of disease severity, age, and ethnicity on the strength and breadth of the humoral response in a multi-ethnic cohort (n = 138). As expected, patients with severe disease showed significantly higher antibody titers and interestingly also had significantly broader epitope coverage. A significant increase in antibody titer and epitope coverage was observed with increasing age, in both mild and severe disease, which is promising for vaccine efficacy in older in iduals. Additionally, we observed significant differences in the breadth and strength of the humoral immune response in relation to ethnicity, which may reflect differences in genetic and lifestyle factors. Furthermore, our data enabled localization of the immuno-dominant epitope to the C-terminal structural domain of the viral nucleocapsid protein in two independent cohorts. Overall, we have designed, validated, and tested an advanced serological assay that enables accurate quantitation of the humoral response post natural infection and that has revealed unexpected differences in the magnitude and epitope utilization within a population.
Publisher: Cold Spring Harbor Laboratory
Date: 27-09-2020
DOI: 10.1101/2020.09.25.20201269
Abstract: Following the COVID-19 pandemic outbreak in late 2019, a large number of antibody tests were developed for use in seroprevalence studies aimed at determining the extent of current or previous SARS-CoV-2 virus infections in a given population. The vast majority of these tests are qualitative and use a single target for antibody detection, incorporating either full-length or truncated versions of the nucleocapsid (N) or spike (S) proteins from SARS-CoV-2. Importantly, mono-epitope tests – whether qualitative or quantitative - are unable to localise antibody binding or characterise the distribution and titres of epitope recognition by anti-SARS-CoV-2 antibodies within an in idual or across a population. However, it seems plausible that if such information were available, it may correlate with the presence of potent, high-titre, neutralising antibodies that afford protection again imminent re-infection, as well as with the likelihood of developing a memory B-cell response that would provide more durable protection. We have developed a novel, quantitative, multi-antigen, multiplexed, array-based immunoassay platform, ‘ImmuSAFE COVID+’ (ImmuSAFE) comprising 6 functionally validated domains or regions of the N protein of SARS-CoV-2 expressed using Sengenics’ KREX technology. This array platform enables determination of both the position and breadth of anti-SARS-CoV-2 antibody responses following natural infection or vaccination. To validate our platform, 100 serum s les (confirmed sero-positive COVID-19 cases, n=50 pre-pandemic HIV positive controls, n=50) were tested for IgG seropositivity to the N antigen, yielding 100% specificity and 100% sensitivity. All 50 cases showed positive antibody reactivity towards at least one N protein epitope, whilst all 50 controls showed antibody reactivity below threshold values. Broad variation was also observed in the magnitude and breadth of antibodies present, represented as an Epitope Coverage score (EPC). A positive correlation was observed between increasing age and EPC values, with in iduals under 40 years old having a mean EPC score of 3.1, whilst in iduals above the age of 60 had a mean EPC of 5.1. This finding may have broad implications for the natural history of COVID-19 disease in different in iduals.
Publisher: MDPI AG
Date: 26-04-2020
DOI: 10.3390/BIOMEDICINES8050097
Abstract: Abnormal immune reactivity in patients with beta-thalassemia (beta-thal) major can be associated with poor prognosis. Immunome protein-array analysis represents a powerful approach to identify novel biomarkers. The Sengenics Immunome Protein Array platform was used for high-throughput quantification of autoantibodies in 12 serum s les collected from nine beta-thal major patients and three non-thalassemia controls, which were run together with two pooled normal sera (Sengenics Internal QC s les). To obtain more accurate and reliable results, the evaluation of the biological relevance of the shortlisted biomarkers was analyzed using an Open Target Platform online database. Elevated autoantibodies directed against 23 autoantigens on the immunome array were identified and analyzed using a penetrance fold change-based bioinformatics method. Understanding the autoantibody profile of beta-thal major patients would help to further understand the pathogenesis of the disease. The identified autoantigens may serve as potential biomarkers for the prognosis of beta-thal major.
No related grants have been discovered for Nur Diana Anuar.