Modeling of waning immunity after SARS-CoV-2 vaccination and influencing factors

Laura Pérez-Alós*, Jose Juan Almagro Armenteros, Johannes Roth Madsen, Cecilie Bo Hansen, Ida Jarlhelt, Sebastian Rask Hamm, Line Dam Heftdal, Mia Marie Pries-Heje, Dina Leth Møller, Kamille Fogh, Rasmus Bo Hasselbalch, Anne Rosbjerg, Søren Brunak, Erik Sørensen, Margit Anita Hørup Larsen, Sisse Rye Ostrowski, Ruth Frikke-Schmidt, Rafael Bayarri-Olmos, Linda Maria Hilsted, Kasper Karmark IversenHenning Bundgaard, Susanne Dam Nielsen, Peter Garred*

*Corresponding author for this work


SARS-CoV-2 vaccines are crucial in controlling COVID-19, but knowledge of which factors determine waning immunity is limited. We examined antibody levels and T-cell gamma-interferon release after two doses of BNT162b2 vaccine or a combination of ChAdOx1-nCoV19 and BNT162b2 vaccines for up to 230 days after the first dose. Generalized mixed models with and without natural cubic splines were used to determine immunity over time. Antibody responses were influenced by natural infection, sex, and age. IgA only became significant in naturally infected. A one-year IgG projection suggested an initial two-phase response in those given the second dose delayed (ChAdOx1/BNT162b2) followed by a more rapid decrease of antibody levels. T-cell responses correlated significantly with IgG antibody responses. Our results indicate that IgG levels will drop at different rates depending on prior infection, age, sex, T-cell response, and the interval between vaccine injections. Only natural infection mounted a significant and lasting IgA response.

Original languageEnglish
Article number1614
JournalNature Communications
Issue number1
Publication statusPublished - Dec 2022


  • Antibodies, Viral
  • BNT162 Vaccine
  • COVID-19/prevention & control
  • COVID-19 Vaccines
  • Humans
  • SARS-CoV-2
  • Vaccination
  • Vaccines, Inactivated
  • Viral Vaccines


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