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

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. · Journal of Infection (2025) · DOI: 10.1016/j.jinf.2025.106436

Resumen

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.