Distinguishing SARS-CoV-2 infection and vaccine responses up to 18 months post-infection using nucleocapsid protein and receptor-binding domain antibodies

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The prediction of the durability of immunity against COVID-19 is relevant, and longitudinal studies are essential for unraveling the details regarding protective SARS‐CoV‐2 antibody responses. It has become challenging to discriminate between COVID-19 vaccine- and infection-induced immune responses since all approved vaccines in Europe and the USA are based on the viral spike (S) protein, which is also the most commonly used antigen in immunoassays measuring immunoglobulins (Igs) against SARS-CoV-2. We have developed a nucleocapsid (N) protein-based sandwich ELISA for detecting pan anti-SARS-CoV-2 Ig with a sensitivity and specificity of 97%. Generalized mixed models were used to determine the degree of long‐term humoral immunity against the N protein and the receptor-binding domain (RBD) of the S protein in a cohort of infected individuals to distinguish between COVID-19 vaccine- and infection-induced immunity. N-specific waning could be observed in individuals who did not experience reinfection, while individuals who experienced reinfection had a new significant increase in N-specific Ig levels. In individuals that seroconverted without a reinfection, 70.1% remained anti-N seropositive after 550 days. The anti-RBD Ig dynamics were unaffected by reinfection but exhibited a clear increase in RBD-specific Ig when vaccination was initiated. In conclusion, a clear difference in the dynamics of the antibody response against N protein and RBD was observed over time. Anti-N protein-specific Igs can be detected up to 18 months after SARS-CoV-2 infection allowing long-term discrimination of infectious and vaccine antibody responses.
TidsskriftMicrobiology Spectrum
Udgave nummer5
Antal sider16
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This work was supported by grants from the Carlsberg Foundation (CF20-476 0045), the Novo Nordisk Foundation (NFF205A0063505 and NNF20SA0064201), the Svend Andersen Research Foundation (SARF2021), and the cooperation Nótaskip.

Publisher Copyright:
Copyright © 2023 Jarlhelt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

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