Preprint Brief Report Version 1 Preserved in Portico This version is not peer-reviewed

Epitope Coverage of Anti-SARS-CoV-2 Nucleocapsid IgA and IgG Antibodies Correlates With Protection Against Re-Infection by New Variants in Subsequent Waves of the COVID-19 Pandemic

Version 1 : Received: 23 December 2022 / Approved: 27 December 2022 / Online: 27 December 2022 (10:43:18 CET)

A peer-reviewed article of this Preprint also exists.

Mullins, M.O.; Smith, M.; Maboreke, H.; Nel, A.J.M.; Ntusi, N.A.B.; Burgers, W.A.; Blackburn, J.M. Epitope Coverage of Anti-SARS-CoV-2 Nucleocapsid IgA and IgG Antibodies Correlates with Protection against Re-Infection by New Variants in Subsequent Waves of the COVID-19 Pandemic. Viruses 2023, 15, 584. Mullins, M.O.; Smith, M.; Maboreke, H.; Nel, A.J.M.; Ntusi, N.A.B.; Burgers, W.A.; Blackburn, J.M. Epitope Coverage of Anti-SARS-CoV-2 Nucleocapsid IgA and IgG Antibodies Correlates with Protection against Re-Infection by New Variants in Subsequent Waves of the COVID-19 Pandemic. Viruses 2023, 15, 584.

Abstract

The COVID-19 pandemic continues to affect individuals across the globe, with some individuals experiencing more severe disease than others. The relatively high frequency of re-infections and breakthrough infections observed with SARS-CoV-2 highlights the importance of extending our understanding of immunity to COVID-19. Here we aim to shed light on the importance of antibody titers and epitope utilization in protection from re-infection. Health care workers are highly exposed to COVID-19 and are therefore also more likely to become re-infected. We utilized quantitative, multi-antigen, multi-epitope SARS-CoV-2 protein microarrays to measure IgG and IgA titers against various domains of the nucleocapsid and spike proteins. Potential re-infections in a large, diverse health care worker cohort (N=300) during the second wave of the pandemic were identified by assessing the IgG anti-N titers before and after the second wave. We assessed epitope coverage and antibody titers between the 'single infection’ and ‘re-infection’ groups. Clear differences were observed in the breadth of the anti-N response before the second wave, with the epitope coverage for both IgG (p=0.019) and IgA (p=0.015) being significantly increased in those who did not become re-infected compared to those who did. Additionally, the IgG anti-N (p=0.004) and anti-S titers (p=0.018) were significantly higher in those not re-infected. These results highlight the importance of the breadth of elicited antibody epitope coverage following natural infection in protection from re-infection and disease in the COVID-19 pandemic.

Keywords

immunoassay; epitope coverage; quantitative antibody binding; protein microarray; SARS-CoV-2 antibodies; humoral response; SARS-CoV-2 re-infection

Subject

Biology and Life Sciences, Immunology and Microbiology

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