Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1-nCoV19 and BNT162b2: a prospective cohort study
Authors: Hillus David , Schwarz Tatjana , Tober-Lau Pinkus , Hastor Hana , Thibeault Charlotte , Kasper Stefanie , Helbig Elisa T. , Lippert Lena J. , Tscheak Patricia , Schmidt Marie Luisa , Riege Johanna , Solarek André , Kalle Christof von , Dang-Heine Chantip , Kopankiewicz Piotr , Suttorp Norbert , Drosten Christian , Bias Harald , Seybold Joachim ,   EICOV/COVIM Study Group, Conrad Claudia , Steuer Doris , Gläser Ute , Sinnigen Anne-Sophie , Rubisch Carolin , Olk Nadine , Hasler Lisbeth , Sanchez-Rezza Angela , Kronenberg Paolo , Horn Alexandra , Koch Willi , Stubbemann Paula , Gabelich Julie-Anne , Münn Friederike , Tesch Julia , Mackeldanz Petra , Bergfeld Leon , Bleicker Tobias , Beheim-Schwarzbach Jörn Ilmo , Hiller Anna , Brumhard Sophia , Bardtke Lara , Pohl Kai , Wendisch Daniel , Georg Philipp , Treue Denise , Briesemeister Dana , Schlesinger Jenny , Hetey Andreas , Kegel Luisa , Richter Annelie , Al-Rim Ben , Maeß Birgit , Behn Kerstin , Lysi Michelle , Zvorc Saskia , Rönnefarth Maria , Schmidt Sein , Krannich Alexander , Schellenberger Isabelle , Schwanitz Georg , Schenkel Viktoria , Bethke Norma , Hülso Claudia , Dieckmann Sebastian , Peiser Christian , Kurth Florian , Corman Victor Max , Sander Leif Erik 
Published: May 2021

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 Charité - Universitätsmedizin 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.