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; Reinhold Förster

doi:10.1038/s41467-022-32527-2

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

31 Citations (Scopus)

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.

Original language	English
Article number	4872
Journal	Nature Communications
Volume	13
Issue number	1
ISSN	1751-8628
DOIs	https://doi.org/10.1038/s41467-022-32527-2
Publication status	Published - 12.2022

Funding

This work was supported by the German Center for Infection Research TTU 01.938 (grant no 80018019238 to G.M.N.B and R.F.), and TTU 04.820 to G.M.N.B., by Deutsche Forschungsgemeinschaft, (DFG, German Research Foundation) Excellence Strategy EXC 2155 “RESIST” (Project ID39087428 to R.F.), by funds of the State of Lower Saxony (14-76103-184 CORONA-11/20 to R.F.), by funds of the BMBF (NaFoUniMedCovid19 FKZ: 01KX2021; Projects B-FAST to R.F.) and Deutsche Forschungsgemeinschaft, SFB 900/3 (Projects B1, 158989968 to R.F.), and the European Regional Development Fund (Defeat Corona, ZW7-8515131 to A.D-J. and G.M.N.B. and ZW7-85151373 to G.M.N.B.). We thank the CoCo Study participants for their support and the entire CoCo study team for help. We would like to thank Luis Manthey, Annika Heidemann, Till Redeker, Madeleine Rommel, Christian Sturm, Marie Mikuteit, Jacqueline Niewolik, Ruth Sikora, Janine Topal, Kerstin Sträche, Birgit Heinisch, Michael Stephan, Mariel Nöhre, Simone Müller, Olivera Dragicevic, Kim Do Thi Hoang, Amy Kempf, and Inga Nehlmeier for technical and logistical support.

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

2.21-04 Virology
2.21-05 Immunology
2.11-04 Structural Biology

Coronavirus related work

Research on SARS-CoV-2 / COVID-19

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-022-32527-2

Cite this

Behrens, G. M. N., Barros-Martins, J., Cossmann, A., Ramos, G. M., Stankov, M. V., Odak, I., Dopfer-Jablonka, A., Hetzel, L., Köhler, M., Patzer, G., Binz, C., Ritter, C., Friedrichsen, M., Schultze-Florey, C., Ravens, I., Willenzon, S., Bubke, A., Ristenpart, J., Janssen, A., ... Förster, R. (2022). BNT162b2-boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19. Nature Communications, 13(1), Article 4872. https://doi.org/10.1038/s41467-022-32527-2

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

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.",

author = "Behrens, \{Georg M.N.\} and Joana Barros-Martins and Anne Cossmann and Ramos, \{Gema Morillas\} and Stankov, \{Metodi V.\} and Ivan Odak and Alexandra Dopfer-Jablonka and Laura Hetzel and Miriam K{\"o}hler and Gwendolyn Patzer and Christoph Binz and Christiane Ritter and Michaela Friedrichsen and Christian Schultze-Florey and Inga Ravens and Stefanie Willenzon and Anja Bubke and Jasmin Ristenpart and Anika Janssen and George Ssebyatika and Verena Kr{\"a}hling and G{\"u}nter Bernhardt and Markus Hoffmann and Stefan P{\"o}hlmann and Thomas Krey and Berislav Bo{\v s}njak and Hammerschmidt, \{Swantje I.\} and Reinhold F{\"o}rster",

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Behrens, GMN, Barros-Martins, J, Cossmann, A, Ramos, GM, Stankov, MV, Odak, I, Dopfer-Jablonka, A, Hetzel, L, Köhler, M, Patzer, G, Binz, C, Ritter, C, Friedrichsen, M, Schultze-Florey, C, Ravens, I, Willenzon, S, Bubke, A, Ristenpart, J, Janssen, A, Ssebyatika, G, Krähling, V, Bernhardt, G, Hoffmann, M, Pöhlmann, S, Krey, T, Bošnjak, B, Hammerschmidt, SI & Förster, R 2022, 'BNT162b2-boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19', Nature Communications, vol. 13, no. 1, 4872. https://doi.org/10.1038/s41467-022-32527-2

TY - JOUR

T1 - BNT162b2-boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19

AU - Behrens, Georg M.N.

AU - Barros-Martins, Joana

AU - Cossmann, Anne

AU - Ramos, Gema Morillas

AU - Stankov, Metodi V.

AU - Odak, Ivan

AU - Dopfer-Jablonka, Alexandra

AU - Hetzel, Laura

AU - Köhler, Miriam

AU - Patzer, Gwendolyn

AU - Binz, Christoph

AU - Ritter, Christiane

AU - Friedrichsen, Michaela

AU - Schultze-Florey, Christian

AU - Ravens, Inga

AU - Willenzon, Stefanie

AU - Bubke, Anja

AU - Ristenpart, Jasmin

AU - Janssen, Anika

AU - Ssebyatika, George

AU - Krähling, Verena

AU - Bernhardt, Günter

AU - Hoffmann, Markus

AU - Pöhlmann, Stefan

AU - Krey, Thomas

AU - Bošnjak, Berislav

AU - Hammerschmidt, Swantje I.

AU - Förster, Reinhold

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85136086399

U2 - 10.1038/s41467-022-32527-2

DO - 10.1038/s41467-022-32527-2

M3 - Journal articles

C2 - 35982040

AN - SCOPUS:85136086399

SN - 1751-8628

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4872

ER -

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

Abstract

Funding

Research Areas and Centers

DFG Research Classification Scheme

Coronavirus related work

UN SDGs

Access to Document

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