BNT162b2-boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19

Georg M.N. Behrens*, Joana Barros-Martins, Anne Cossmann, Gema Morillas Ramos, Metodi V. Stankov, Ivan Odak, Alexandra Dopfer-Jablonka, Laura Hetzel, Miriam Köhler, Gwendolyn Patzer, Christoph Binz, Christiane Ritter, Michaela Friedrichsen, Christian Schultze-Florey, Inga Ravens, Stefanie Willenzon, Anja Bubke, Jasmin Ristenpart, Anika Janssen, George SsebyatikaVerena Krähling, Günter Bernhardt, Markus Hoffmann, Stefan Pöhlmann, Thomas Krey, Berislav Bošnjak, Swantje I. Hammerschmidt, Reinhold Förster*

*Corresponding author for this work
21 Citations (Scopus)


Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) has been reported to be superior in inducing protective immunity compared to repeated application of the same vaccine. However, data comparing immunity decline after homologous and heterologous vaccination as well as effects of a third vaccine application after heterologous ChAd/BNT vaccination are lacking. Here we show longitudinal monitoring of ChAd/ChAd (n = 41) and ChAd/BNT (n = 88) vaccinated individuals and the impact of a third vaccination with BNT. The third vaccination greatly augments waning anti-spike IgG but results in only moderate increase in spike-specific CD4 + and CD8 + T cell numbers in both groups, compared to cell frequencies already present after the second vaccination in the ChAd/BNT group. More importantly, the third vaccination efficiently restores neutralizing antibody responses against the Alpha, Beta, Gamma, and Delta variants of the virus, but neutralizing activity against the B.1.1.529 (Omicron) variant remains severely impaired. In summary, inferior SARS-CoV-2 specific immune responses following homologous ChAd/ChAd vaccination can be compensated by heterologous BNT vaccination, which might influence the choice of vaccine type for subsequent vaccination boosts.

Original languageEnglish
Article number4872
JournalNature Communications
Issue number1
Publication statusPublished - 12.2022

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Structural and Cell Biology (CSCM/ZMSZ)

DFG Research Classification Scheme

  • 204-04 Virology
  • 204-05 Immunology
  • 201-04 Structural Biology

Coronavirus related work

  • Research on SARS-CoV-2 / COVID-19

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