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Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1-nCoV19 and BNT162b2: a prospective cohort study

By David Hillus, Tatjana Schwarz, Pinkus Tober-Lau, Hana Hastor, Charlotte Thibeault, Stefanie Kasper, Elisa T. Helbig, Lena J. Lippert, Patricia Tscheak, Marie Luisa Schmidt, Johanna Riege, Andr Solarek, Christof von Kalle, Chantip Dang-Heine, Piotr Kopankiewicz, Norbert Suttorp, Christian Drosten, Harald Bias, Joachim Seybold, COVIM/EICOV Study Group, Florian Kurth, Victor M Corman, Leif Erik Sander

Posted 22 May 2021
medRxiv DOI: 10.1101/2021.05.19.21257334

Objective: to assess reactogenicity and immunogenicity of heterologous prime-boost immunisations of ChAdOx1-nCoV19 (Vaxzevria, ChAdOx) followed by BNT162b2 (Comirnaty, BNT) compared to homologous BNT/BNT immunisation. Design: prospective, observational cohort study. Setting: unicenter study in a cohort of health care workers at a tertiary care center in Berlin, Germany. Participants: 340 health care workers immunised between 27 December 2020 and 21 May 2021 at Charite - Universitaetsmedizin Berlin, Germany Main outcome measures: the main outcomes were reactogenicity assessed on days one, three, five and seven post prime and boost vaccination, and immunogenicity measured by serum SARS-CoV-2 full spike-, spike S1-, and spike RBD-IgG, virus neutralisation capacity, anti-S1-IgG avidity, and T cell reactivity measured by Interferon gamma release assay at 3-4 weeks post prime and boost immunisation. Results: Heterologous ChAdOx/BNT booster vaccination was overall well-tolerated and reactogenicity was largely comparable to homologous BNT/BNT vaccination. Systemic reactions were most frequent after prime immunisation with ChAdOx (86%, 95CI: 79-91), and less frequent after homologous BNT/BNT (65%, 95CI: 56-72), or heterologous ChAdOx/BNT booster vaccination (48%, 95CI: 36-59). Serum antibody responses and T cell reactivity were strongly increased after both homologous and heterologous boost, and immunogenicity was overall robust, and comparable between both regimens in this cohort, with slightly increased S1-IgG avidity and T cell responses following heterologous booster immunisation. Conclusions: Evidence of rare thrombotic events associated with ChAdOx has led to recommendation of a heterologous booster with mRNA vaccines for certain age groups in several European countries, despite a lack of robust safety and immunogenicity data for this vaccine regimen. This interim analysis provides evidence that the currently recommended heterologous ChAdOx/BNT immunisation regimen with 10-12 week vaccine intervals is well tolerated and slightly more immunogenic compared to homologous BNT/BNT vaccination with three week vaccine intervals. Heterologous prime-boost immunisation for COVID-19 may be generally applicable to optimise logistics and improve immunogenicity and to mitigate potential intermittent supply shortages for individual vaccines.

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