Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response

C. C.A. Noble; E. McDonald; S. Nicholson; S. Biering-Sørensen; L. F. Pittet; A. L. Byrne; J. Croda; M. Dalcolmo; M. V.G. Lacerda; M. Lucas; D. J. Lynn; C. Prat Aymerich; P. C. Richmond; A. Warris; N. Curtis; N. L. Messina

doi:10.1016/j.jinf.2025.106436

Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response

C. C.A. Noble^*, E. McDonald, S. Nicholson, S. Biering-Sørensen, L. F. Pittet, A. L. Byrne, J. Croda, M. Dalcolmo, M. V.G. Lacerda, M. Lucas, D. J. Lynn, C. Prat Aymerich, P. C. Richmond, A. Warris, N. Curtis, N. L. Messina

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Objectives: SARS-CoV-2 nucleocapsid (N) protein antibodies can be used to identify the serological response to natural infection in those who have previously received a COVID-19 spike-based vaccine. Anti-N antibody responses can also be induced by inactivated whole SARS-CoV-2 virus vaccines, such as CoronaVac. We aimed to characterise antibody responses to the N protein following COVID-19 and following vaccination with CoronaVac. Methods: Using participants from an international randomised controlled trial, we investigated the evolution of anti-N antibody responses over time in two separate groups: adults following COVID-19, and in adults following vaccination with CoronaVac. Results: In 212 participants who had COVID-19, the anti-N seroconversion rate was 96.9% in those infected following an incomplete course of COVID-19 (spike-based) vaccinations and 88.2% in those infected following a complete course. Anti-N antibody indices were highly variable between participants, and higher in participants who had more severe COVID-19 symptoms, were aged ≥60 years, were unvaccinated, had comorbidities and those resident in Brazil. Most participants remained seropositive after 12 months. In 317 separate participants, the anti-N seroconversion rate was 63.5% following CoronaVac vaccination, with variable antibody indices. Conclusions: Anti-N responses to COVID-19 and CoronaVac are highly variable but persistent. A prior complete course of COVID-19 spike-based vaccination reduced both anti-N seroconversion and antibody indices following COVID-19.

Original language	English
Article number	106436
Journal	Journal of Infection
Volume	90
Issue number	3
DOIs	https://doi.org/10.1016/j.jinf.2025.106436
Publication status	Published - Mar 2025

Keywords

Anti-N
Antibody
CoronaVac
COVID-19
Nucleocapsid protein
SARS-CoV-2
Seroconversion
Vaccination

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Noble, C. C. A., McDonald, E., Nicholson, S., Biering-Sørensen, S., Pittet, L. F., Byrne, A. L., Croda, J., Dalcolmo, M., Lacerda, M. V. G., Lucas, M., Lynn, D. J., Prat Aymerich, C., Richmond, P. C., Warris, A., Curtis, N., & Messina, N. L. (2025). Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response. Journal of Infection, 90(3), Article 106436. https://doi.org/10.1016/j.jinf.2025.106436

@article{7531adafc4da4eb4bf2cf24ab27c8e0c,

title = "Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response",

abstract = "Objectives: SARS-CoV-2 nucleocapsid (N) protein antibodies can be used to identify the serological response to natural infection in those who have previously received a COVID-19 spike-based vaccine. Anti-N antibody responses can also be induced by inactivated whole SARS-CoV-2 virus vaccines, such as CoronaVac. We aimed to characterise antibody responses to the N protein following COVID-19 and following vaccination with CoronaVac. Methods: Using participants from an international randomised controlled trial, we investigated the evolution of anti-N antibody responses over time in two separate groups: adults following COVID-19, and in adults following vaccination with CoronaVac. Results: In 212 participants who had COVID-19, the anti-N seroconversion rate was 96.9% in those infected following an incomplete course of COVID-19 (spike-based) vaccinations and 88.2% in those infected following a complete course. Anti-N antibody indices were highly variable between participants, and higher in participants who had more severe COVID-19 symptoms, were aged ≥60 years, were unvaccinated, had comorbidities and those resident in Brazil. Most participants remained seropositive after 12 months. In 317 separate participants, the anti-N seroconversion rate was 63.5% following CoronaVac vaccination, with variable antibody indices. Conclusions: Anti-N responses to COVID-19 and CoronaVac are highly variable but persistent. A prior complete course of COVID-19 spike-based vaccination reduced both anti-N seroconversion and antibody indices following COVID-19.",

keywords = "Anti-N, Antibody, CoronaVac, COVID-19, Nucleocapsid protein, SARS-CoV-2, Seroconversion, Vaccination",

author = "Noble, {C. C.A.} and E. McDonald and S. Nicholson and S. Biering-S{\o}rensen and Pittet, {L. F.} and Byrne, {A. L.} and J. Croda and M. Dalcolmo and Lacerda, {M. V.G.} and M. Lucas and Lynn, {D. J.} and {Prat Aymerich}, C. and Richmond, {P. C.} and A. Warris and N. Curtis and Messina, {N. L.}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = mar,

doi = "10.1016/j.jinf.2025.106436",

language = "English",

volume = "90",

journal = "Journal of Infection",

issn = "0163-4453",

publisher = "W.B. Saunders Ltd",

number = "3",

}

Noble, CCA, McDonald, E, Nicholson, S, Biering-Sørensen, S, Pittet, LF, Byrne, AL, Croda, J, Dalcolmo, M, Lacerda, MVG, Lucas, M, Lynn, DJ, Prat Aymerich, C, Richmond, PC, Warris, A, Curtis, N & Messina, NL 2025, 'Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response', Journal of Infection, vol. 90, no. 3, 106436. https://doi.org/10.1016/j.jinf.2025.106436

TY - JOUR

T1 - Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response

AU - Noble, C. C.A.

AU - McDonald, E.

AU - Nicholson, S.

AU - Biering-Sørensen, S.

AU - Pittet, L. F.

AU - Byrne, A. L.

AU - Croda, J.

AU - Dalcolmo, M.

AU - Lacerda, M. V.G.

AU - Lucas, M.

AU - Lynn, D. J.

AU - Prat Aymerich, C.

AU - Richmond, P. C.

AU - Warris, A.

AU - Curtis, N.

AU - Messina, N. L.

PY - 2025/3

Y1 - 2025/3

N2 - Objectives: SARS-CoV-2 nucleocapsid (N) protein antibodies can be used to identify the serological response to natural infection in those who have previously received a COVID-19 spike-based vaccine. Anti-N antibody responses can also be induced by inactivated whole SARS-CoV-2 virus vaccines, such as CoronaVac. We aimed to characterise antibody responses to the N protein following COVID-19 and following vaccination with CoronaVac. Methods: Using participants from an international randomised controlled trial, we investigated the evolution of anti-N antibody responses over time in two separate groups: adults following COVID-19, and in adults following vaccination with CoronaVac. Results: In 212 participants who had COVID-19, the anti-N seroconversion rate was 96.9% in those infected following an incomplete course of COVID-19 (spike-based) vaccinations and 88.2% in those infected following a complete course. Anti-N antibody indices were highly variable between participants, and higher in participants who had more severe COVID-19 symptoms, were aged ≥60 years, were unvaccinated, had comorbidities and those resident in Brazil. Most participants remained seropositive after 12 months. In 317 separate participants, the anti-N seroconversion rate was 63.5% following CoronaVac vaccination, with variable antibody indices. Conclusions: Anti-N responses to COVID-19 and CoronaVac are highly variable but persistent. A prior complete course of COVID-19 spike-based vaccination reduced both anti-N seroconversion and antibody indices following COVID-19.

AB - Objectives: SARS-CoV-2 nucleocapsid (N) protein antibodies can be used to identify the serological response to natural infection in those who have previously received a COVID-19 spike-based vaccine. Anti-N antibody responses can also be induced by inactivated whole SARS-CoV-2 virus vaccines, such as CoronaVac. We aimed to characterise antibody responses to the N protein following COVID-19 and following vaccination with CoronaVac. Methods: Using participants from an international randomised controlled trial, we investigated the evolution of anti-N antibody responses over time in two separate groups: adults following COVID-19, and in adults following vaccination with CoronaVac. Results: In 212 participants who had COVID-19, the anti-N seroconversion rate was 96.9% in those infected following an incomplete course of COVID-19 (spike-based) vaccinations and 88.2% in those infected following a complete course. Anti-N antibody indices were highly variable between participants, and higher in participants who had more severe COVID-19 symptoms, were aged ≥60 years, were unvaccinated, had comorbidities and those resident in Brazil. Most participants remained seropositive after 12 months. In 317 separate participants, the anti-N seroconversion rate was 63.5% following CoronaVac vaccination, with variable antibody indices. Conclusions: Anti-N responses to COVID-19 and CoronaVac are highly variable but persistent. A prior complete course of COVID-19 spike-based vaccination reduced both anti-N seroconversion and antibody indices following COVID-19.

KW - Anti-N

KW - Antibody

KW - CoronaVac

KW - COVID-19

KW - Nucleocapsid protein

KW - SARS-CoV-2

KW - Seroconversion

KW - Vaccination

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U2 - 10.1016/j.jinf.2025.106436

DO - 10.1016/j.jinf.2025.106436

M3 - Article

C2 - 39922387

AN - SCOPUS:85219126202

SN - 0163-4453

VL - 90

JO - Journal of Infection

JF - Journal of Infection

IS - 3

M1 - 106436

ER -

Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response

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Keywords

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