Omicron infection-associated T- and B-cell immunity in antigen-naive and triple-COVID-19-vaccinated individuals

Joana Barros-Martins, Swantje I. Hammerschmidt, Gema Morillas Ramos, Anne Cossmann, Laura Hetzel, Ivan Odak, Miriam Köhler, Metodi V. Stankov, Christiane Ritter, Michaela Friedrichsen, Inga Ravens, Anja Schimrock, Jasmin Ristenpart, Anika Janssen, Stefanie Willenzon, Günter Bernhardt, Ralf Lichtinghagen, Berislav Bošnjak, Georg M.N. Behrens, Reinhold Förster

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Since early 2022, various Omicron variants have dominated the SARS-CoV-2 pandemic in most countries. All Omicron variants are B-cell immune escape variants, and antibodies induced by first-generation COVID-19 vaccines or by infection with earlier SARS-CoV-2 variants largely fail to protect individuals from Omicron infection. In the present study, we investigated the effect of Omicron infections in triple-vaccinated and in antigen-naive individuals. We show that Omicron breakthrough infections occurring 2–3.5 months after the third vaccination restore B-cell and T-cell immune responses to levels similar to or higher than those measured 14 days after the third vaccination, including the induction of Omicron-neutralizing antibodies. Antibody responses in breakthrough infection derived mostly from cross-reacting B cells, initially induced by vaccination, whereas Omicron infections in antigen-naive individuals primarily generated B cells binding to the Omicron but not the Wuhan spike protein. Although antigen-naive individuals mounted considerable T-cell responses after infection, B-cell responses were low, and neutralizing antibodies were frequently below the limit of detection. In summary, the detection of Omicron-associated B-cell responses in primed and in antigen-naive individuals supports the application of Omicron-adapted COVID-19 vaccines, but calls into question their suitability if they also contain/encode antigens of the original Wuhan virus.

Original languageEnglish
Article number1166589
JournalFrontiers in Immunology
StatePublished - 2023
Externally publishedYes


  • COVID-19
  • Omicron infection
  • Omicron variants
  • SARS-CoV-2
  • breakthrough infection
  • heterologous vaccination


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