From first infection to reinfection: Comparing Nucleocapsid antibody kinetics in vaccinated and unvaccinated adults

Vaccine. 2025 Aug 30:62:127593. doi: 10.1016/j.vaccine.2025.127593. Epub 2025 Aug 13.

Abstract

Objectives: Determining infection histories of individuals with prior immunity is critical to studying SARS-CoV-2 imprinting and vaccine responses. To better understand the response to infection, we examine nucleocapsid protein antibody dynamics around first and second SARS-CoV-2 infections in vaccinated and unvaccinated adults.

Methods: The presence and levels of nucleocapsid-antibodies were measured around first and second SARS-CoV-2 infections. Antibody waning was measured with accelerated failure time models.

Results: After first-infections 95.8 % (88.5-98.6 %) of unvaccinated and 89.4 % (86.5-91.7 %) of vaccinated participants seroconverted. Vaccinated adults had 45.5 % shorter seropositivity (event time ratio = 0.55, 95 %CI: 0.45-0.66). After second-infections, 89.1 % (76.9-95.3 %) of vaccinated and 94.4 % (74.2-99.0 %) of unvaccinated participants had a 4-fold rise in antibody levels. Regardless of vaccination, antibody levels after second-infections are significantly higher than after first-infections.

Conclusions: These findings suggest nucleocapsid serology can inform researchers about past infections regardless of exposure status, and potentially differentiate between initial infections and reinfections.

Keywords: Epidemiology; Nucleocapsid; SARS-Cov-2; Serology; Vaccination.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Coronavirus Nucleocapsid Proteins* / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nucleocapsid* / immunology
  • Reinfection* / immunology
  • SARS-CoV-2* / immunology
  • Vaccination
  • Young Adult

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • Coronavirus Nucleocapsid Proteins