Objectives: SARS-CoV-2 nucleocapsid (N) protein antibodies can be used to detect the serological response to natural infection in those previously receiving a COVID-19 spike-based vaccine. Anti-N antibody responses can also be detected in those receiving 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: following COVID-19, or 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 fully vaccinated. 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 COVID-19 spike-based vaccination course reduced both anti-N seroconversion and antibody indices following COVID-19.