Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort

Autor: Nishant N. Vaikath, Khalid Ouararhni, Wendy A. Burgers, Adviti Naik, Elizabeth S Mayne, Nur Hafiza Ismail, Michelle Mullins, Darien T. Schell, Omar M. A. El-Agnaf, Nur Diana Anuar, Mohammed Al-Maadheed, Maryam Ali Al-Nesf, Kavithambigai Ellan, Ilham Bensmail, Arif Anwar, Nurul Shielawati Mohamed Rosli, Nour K. Majbour, Vidya Mohamed-Ali, Priscilla E. Morris, Rozainanee Mohd Zain, Seanantha S. Baros-Steyl, Andrew J.M. Nel, Muneerah Smith, Houari Abdesselem, Ti-Myen Tan, Raja Nurashirin Raja Mamat, Jonathan M. Blackburn
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Microarray
Antibodies
Viral
Severity of Illness Index
Epitope
Cohort Studies
Epitopes
0302 clinical medicine
Seroepidemiologic Studies
Ethnicity
030212 general & internal medicine
Antigens
Viral
education.field_of_study
Antibody titer
Middle Aged
Nucleocapsid Proteins
QR1-502
Infectious Diseases
Cohort
Female
humoral response
Adult
Adolescent
Population
Biology
Microbiology
Sensitivity and Specificity
Article
quantitative antibody binding
COVID-19 Serological Testing
Young Adult
03 medical and health sciences
Immune system
SARS-CoV-2 nucleocapsid protein
Virology
Humans
immunoassay
education
Pandemics
epitope coverage
SARS-CoV-2 antibodies
SARS-CoV-2
Viral nucleocapsid
COVID-19
Vaccine efficacy
Immunity
Humoral
030104 developmental biology
protein microarray
Case-Control Studies
Immunoglobulin G
Immunology
Zdroj: Viruses
Volume 13
Issue 5
Viruses, Vol 13, Iss 786, p 786 (2021)
ISSN: 1999-4915
DOI: 10.3390/v13050786
Popis: The COVID-19 pandemic has affected all individuals 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 individuals. 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.
Databáze: OpenAIRE
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