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

Authors:

• 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.

Details:

Journal of Infection, Volume 90, Issue 3, 2025-03-31

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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.