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Comparative studies of SARS-CoV-2 antinucleocapsid (anti-N) antibody response in the context of inactivated virus vaccines versus natural infection are limited. This study aims to determine and compare the anti-N antibody levels in people vaccinated with Sinopharm’s (Wuhan, China) inactivated virus vaccine in comparison with naturally infected unvaccinated and Pfizer’s spike (S) mRNA-based vaccinated subjects. Two hundred ninety-nine Jordanian adults participated in the study including unvaccinated COVID-19-infected patients (n = 99), Pfizer-vaccinated (n = 100), and Sinopharm-vaccinated recipients (n = 100). Serum samples were assayed for anti-N IgG, anti-N IgM, and anti-S IgG. Sera of 64.6% of naturally infected unvaccinated participants had positive anti-S IgG (median = 36.35 U/mL; range: 0.04–532.5 U/mL) compared to 88% of Pfizer-vaccinated (Manhattan, NY, USA) (median = 26.52 U/mL; range: 0.39–1265 U/mL) and 58% of Sinopharm-vaccinated subjects (median = 14.35 U/mL; range: 0.39–870.17 U/mL). Samples of 60.6% of naturally infected unvaccinated people had positive anti-N IgG (median = 15.03 U/mL; range: 0–265.1 U/mL) compared to 25% of Pfizer-vaccinated (median = 0.02 U/mL; range: 0–68 U/mL) and 48% of Sinopharm-vaccinated subjects (median = 0.8 U/mL; range: 0–146.3 U/mL). Anti-N titers among the three groups were significantly different (p &lt; 0.05). Anti-N IgM antibodies appeared in 23.2% of the naturally infected unvaccinated group (median = 0.29 U/mL; range: 0–15 U/mL) compared to only 9.0% of Pfizer-vaccinated (median = 018 U/mL; range: 0–33 U/mL) and 7.0% of Sinopharm-vaccinated subjects (median = 0.2 U/mL; range: 0–12.02 U/mL). A significant negative correlation was found between anti-S and age for both vaccines and between anti-S and the presence of chronic disease in Sinopharm-vaccinated subjects. A significant positive correlation between anti-N and anti-S titers was found among the three groups. This study shows that the inactivated virus vaccine, Sinopharm, induces an anti-N response that can boost that of natural infection or vice versa. On the other hand, the Pfizer mRNA-based vaccine induces a significantly stronger anti-S Ab response.

SARS-CoV-2 Antinucleocapsid Antibody Response of mRNA and Inactivated Virus Vaccines Compared to Unvaccinated Individuals