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

Research output: Contribution to journalJournal articleResearchpeer-review

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Distinguishing SARS-CoV-2 infection and vaccine responses up to 18 months post-infection using nucleocapsid protein and receptor-binding domain antibodies. / Jarlhelt, Ida; Pérez-Alós, Laura; Bayarri-Olmos, Rafael; Hansen, Cecilie Bo; Petersen, Maria Skaalum; Weihe, Pál; Armenteros, Jose Juan Almagro; Madsen, Johannes Roth; Nielsen, Jacob Pohl Stangerup; Hilsted, Linda Maria; Iversen, Kasper Karmark; Bundgaard, Henning; Nielsen, Susanne Dam; Garred, Peter.

In: Microbiology Spectrum, Vol. 11, No. 5, 2023.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Jarlhelt, I, Pérez-Alós, L, Bayarri-Olmos, R, Hansen, CB, Petersen, MS, Weihe, P, Armenteros, JJA, Madsen, JR, Nielsen, JPS, Hilsted, LM, Iversen, KK, Bundgaard, H, Nielsen, SD & Garred, P 2023, 'Distinguishing SARS-CoV-2 infection and vaccine responses up to 18 months post-infection using nucleocapsid protein and receptor-binding domain antibodies', Microbiology Spectrum, vol. 11, no. 5. https://doi.org/10.1128/spectrum.01796-23

APA

Jarlhelt, I., Pérez-Alós, L., Bayarri-Olmos, R., Hansen, C. B., Petersen, M. S., Weihe, P., Armenteros, J. J. A., Madsen, J. R., Nielsen, J. P. S., Hilsted, L. M., Iversen, K. K., Bundgaard, H., Nielsen, S. D., & Garred, P. (2023). Distinguishing SARS-CoV-2 infection and vaccine responses up to 18 months post-infection using nucleocapsid protein and receptor-binding domain antibodies. Microbiology Spectrum, 11(5). https://doi.org/10.1128/spectrum.01796-23

Vancouver

Jarlhelt I, Pérez-Alós L, Bayarri-Olmos R, Hansen CB, Petersen MS, Weihe P et al. Distinguishing SARS-CoV-2 infection and vaccine responses up to 18 months post-infection using nucleocapsid protein and receptor-binding domain antibodies. Microbiology Spectrum. 2023;11(5). https://doi.org/10.1128/spectrum.01796-23

Author

Jarlhelt, Ida ; Pérez-Alós, Laura ; Bayarri-Olmos, Rafael ; Hansen, Cecilie Bo ; Petersen, Maria Skaalum ; Weihe, Pál ; Armenteros, Jose Juan Almagro ; Madsen, Johannes Roth ; Nielsen, Jacob Pohl Stangerup ; Hilsted, Linda Maria ; Iversen, Kasper Karmark ; Bundgaard, Henning ; Nielsen, Susanne Dam ; Garred, Peter. / Distinguishing SARS-CoV-2 infection and vaccine responses up to 18 months post-infection using nucleocapsid protein and receptor-binding domain antibodies. In: Microbiology Spectrum. 2023 ; Vol. 11, No. 5.

Bibtex

@article{1ba72c31a370475eb0485dc898153227,
title = "Distinguishing SARS-CoV-2 infection and vaccine responses up to 18 months post-infection using nucleocapsid protein and receptor-binding domain antibodies",
abstract = "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. IMPORTANCE Longitudinal studies are essential to unravel details regarding the protective antibody responses after COVID-19 infection and vaccination. It has become challenging to distinguish long-term immune responses to SARS-CoV-2 infection and vaccination since most approved vaccines are based on the viral spike (S) protein, which is also mostly used in immunoassays measuring immunoglobulins (Igs) against SARS-CoV-2. We have developed a novel nucleocapsid (N) protein-based sandwich ELISA for detecting pan-anti-SARS-CoV-2 Ig, exhibiting high sensitivity and specificity. Generalized mixed models were used to determine long‐term humoral immunity in a cohort of infected individuals from the Faroe Islands, distinguishing between COVID-19 vaccine- and infection-induced immunity. A clear difference in the dynamics of the antibody response against N protein and S protein was observed over time, and the anti-N protein-specific Igs could be detected up to 18 months after SARS-CoV-2 infection. This enables long-term discrimination between natural infection and vaccine-dependent antibody responses.",
keywords = "antibody duration, nucleocapsid protein, RBD, sandwich antibody ELISA, SARS-CoV-2, spike protein",
author = "Ida Jarlhelt and Laura P{\'e}rez-Al{\'o}s and Rafael Bayarri-Olmos and Hansen, {Cecilie Bo} and Petersen, {Maria Skaalum} and P{\'a}l Weihe and Armenteros, {Jose Juan Almagro} and Madsen, {Johannes Roth} and Nielsen, {Jacob Pohl Stangerup} and Hilsted, {Linda Maria} and Iversen, {Kasper Karmark} and Henning Bundgaard and Nielsen, {Susanne Dam} and Peter Garred",
note = "Publisher Copyright: Copyright {\textcopyright} 2023 Jarlhelt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.",
year = "2023",
doi = "10.1128/spectrum.01796-23",
language = "English",
volume = "11",
journal = "Microbiology spectrum",
issn = "2165-0497",
publisher = "American Society for Microbiology",
number = "5",

}

RIS

TY - JOUR

T1 - Distinguishing SARS-CoV-2 infection and vaccine responses up to 18 months post-infection using nucleocapsid protein and receptor-binding domain antibodies

AU - Jarlhelt, Ida

AU - Pérez-Alós, Laura

AU - Bayarri-Olmos, Rafael

AU - Hansen, Cecilie Bo

AU - Petersen, Maria Skaalum

AU - Weihe, Pál

AU - Armenteros, Jose Juan Almagro

AU - Madsen, Johannes Roth

AU - Nielsen, Jacob Pohl Stangerup

AU - Hilsted, Linda Maria

AU - Iversen, Kasper Karmark

AU - Bundgaard, Henning

AU - Nielsen, Susanne Dam

AU - Garred, Peter

N1 - 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.

PY - 2023

Y1 - 2023

N2 - 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. IMPORTANCE Longitudinal studies are essential to unravel details regarding the protective antibody responses after COVID-19 infection and vaccination. It has become challenging to distinguish long-term immune responses to SARS-CoV-2 infection and vaccination since most approved vaccines are based on the viral spike (S) protein, which is also mostly used in immunoassays measuring immunoglobulins (Igs) against SARS-CoV-2. We have developed a novel nucleocapsid (N) protein-based sandwich ELISA for detecting pan-anti-SARS-CoV-2 Ig, exhibiting high sensitivity and specificity. Generalized mixed models were used to determine long‐term humoral immunity in a cohort of infected individuals from the Faroe Islands, distinguishing between COVID-19 vaccine- and infection-induced immunity. A clear difference in the dynamics of the antibody response against N protein and S protein was observed over time, and the anti-N protein-specific Igs could be detected up to 18 months after SARS-CoV-2 infection. This enables long-term discrimination between natural infection and vaccine-dependent antibody responses.

AB - 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. IMPORTANCE Longitudinal studies are essential to unravel details regarding the protective antibody responses after COVID-19 infection and vaccination. It has become challenging to distinguish long-term immune responses to SARS-CoV-2 infection and vaccination since most approved vaccines are based on the viral spike (S) protein, which is also mostly used in immunoassays measuring immunoglobulins (Igs) against SARS-CoV-2. We have developed a novel nucleocapsid (N) protein-based sandwich ELISA for detecting pan-anti-SARS-CoV-2 Ig, exhibiting high sensitivity and specificity. Generalized mixed models were used to determine long‐term humoral immunity in a cohort of infected individuals from the Faroe Islands, distinguishing between COVID-19 vaccine- and infection-induced immunity. A clear difference in the dynamics of the antibody response against N protein and S protein was observed over time, and the anti-N protein-specific Igs could be detected up to 18 months after SARS-CoV-2 infection. This enables long-term discrimination between natural infection and vaccine-dependent antibody responses.

KW - antibody duration

KW - nucleocapsid protein

KW - RBD

KW - sandwich antibody ELISA

KW - SARS-CoV-2

KW - spike protein

U2 - 10.1128/spectrum.01796-23

DO - 10.1128/spectrum.01796-23

M3 - Journal article

C2 - 37738355

AN - SCOPUS:85175561441

VL - 11

JO - Microbiology spectrum

JF - Microbiology spectrum

SN - 2165-0497

IS - 5

ER -

ID: 375962685