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 Ssebyatika, Verena Krähling, Günter Bernhardt, Markus Hoffmann, Stefan Pöhlmann, Thomas Krey, Berislav Bošnjak, Swantje I. Hammerschmidt and Reinhold Förster ()
Additional contact information
Georg M. N. Behrens: Hannover Medical School
Joana Barros-Martins: Hannover Medical School
Anne Cossmann: Hannover Medical School
Gema Morillas Ramos: Hannover Medical School
Metodi V. Stankov: Hannover Medical School
Ivan Odak: Hannover Medical School
Alexandra Dopfer-Jablonka: Hannover Medical School
Laura Hetzel: Hannover Medical School
Miriam Köhler: Hannover Medical School
Gwendolyn Patzer: Hannover Medical School
Christoph Binz: Hannover Medical School
Christiane Ritter: Hannover Medical School
Michaela Friedrichsen: Hannover Medical School
Christian Schultze-Florey: Hannover Medical School
Inga Ravens: Hannover Medical School
Stefanie Willenzon: Hannover Medical School
Anja Bubke: Hannover Medical School
Jasmin Ristenpart: Hannover Medical School
Anika Janssen: Hannover Medical School
George Ssebyatika: University of Lübeck
Verena Krähling: Philipps University Marburg
Günter Bernhardt: Hannover Medical School
Markus Hoffmann: German Primate Center
Stefan Pöhlmann: German Primate Center
Thomas Krey: University of Lübeck
Berislav Bošnjak: Hannover Medical School
Swantje I. Hammerschmidt: Hannover Medical School
Reinhold Förster: Partner Site Hannover-Braunschweig

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-32527-2

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