Heterologous ChAdOx1/BNT162b2 vaccination induces stronger immune response than homologous ChAdOx1 vaccination: The pragmatic, multi-center, three-arm, partially randomized HEVACC trial
Zoltán Bánki, Jose Mateus, Annika Rössler, Helena Schäfer, David Bante, Lydia Riepler, Alba Grifoni, Alessandro Sette, Viviana Simon, Barbara Falkensammer, Hanno Ulmer, Bianca Neurauter, Wegene Borena, HEVACC Study Group, Florian Krammer, Dorothee von Laer, Daniela Weiskopf, Janine Kimpel, Petra Flatscher, Lukas Forer, Elisabeth Graf, Gerhard Hausberger, Peter Heininger, Michael Kundi, Christine Mantinger, Conny Ower, Daniel Rainer, Magdalena Sacher, Lisa Seekircher, Sebastian Schönherr, Marton Szell, Tobias Trips, Ursula Wiedermann, Peter Willeit, Reinhard Würzner, August Zabernigg, Zoltán Bánki, Jose Mateus, Annika Rössler, Helena Schäfer, David Bante, Lydia Riepler, Alba Grifoni, Alessandro Sette, Viviana Simon, Barbara Falkensammer, Hanno Ulmer, Bianca Neurauter, Wegene Borena, HEVACC Study Group, Florian Krammer, Dorothee von Laer, Daniela Weiskopf, Janine Kimpel, Petra Flatscher, Lukas Forer, Elisabeth Graf, Gerhard Hausberger, Peter Heininger, Michael Kundi, Christine Mantinger, Conny Ower, Daniel Rainer, Magdalena Sacher, Lisa Seekircher, Sebastian Schönherr, Marton Szell, Tobias Trips, Ursula Wiedermann, Peter Willeit, Reinhard Würzner, August Zabernigg
Abstract
Background: Several COVID-19 vaccines have been approved. The mRNA vaccine from Pfizer/BioNTech (Comirnaty, BNT162b2; BNT) and the vector vaccine from AstraZeneca (Vaxzevria, ChAdOx1; AZ) have been widely used. mRNA vaccines induce high antibody and T cell responses, also to SARS-CoV-2 variants, but are costlier and less stable than the slightly less effective vector vaccines. For vector vaccines, heterologous vaccination schedules have generally proven more effective than homologous schedules.
Methods: In the HEVACC three-arm, single-blinded, adaptive design study (ClinicalTrials.gov Identifier: NCT04907331), participants between 18 and 65 years with no prior history of SARS-CoV-2 infection and a first dose of AZ or BNT were included. The AZ/AZ and the AZ/BNT arms were randomized (in a 1:1 ratio stratified by sex and trial site) and single-blinded, the third arm (BNT/BNT) was observational. We compared the reactogenicity between the study arms and hypothesized that immunogenicity was higher for the heterologous AZ/BNT compared to the homologous AZ/AZ regimen using neutralizing antibody titers as primary endpoint.
Findings: This interim analysis was conducted after 234 participants had been randomized and 254 immunized (N=109 AZ/AZ, N=115 AZ/BNZ, N=30 BNT/BNT). Heterologous AZ/BNT vaccination was well tolerated without study-related severe adverse events. Neutralizing antibody titers on day 30 were statistically significant higher in the AZ/BNT and the BNT/BNT groups than in the AZ/AZ group, for B.1.617.2 (Delta) AZ/AZ median reciprocal titer 75.9 (99.9% CI 58.0 - 132.5), AZ/BNT 571.5 (99.9% CI 396.6 - 733.1), and BNT/BNT 404.5 (99.9% CI 68.3 - 1024). Similarly, the frequency and multifunctionality of spike-specific T cell responses was comparable between the AZ/BNT and the BNT/BNT groups, but lower in the AZ/AZ vaccinees.
Interpretation: This study clearly shows the immunogenicity and safety of heterologous AZ/BNT vaccination and encourages further studies on heterologous vaccination schedules.
Funding: This work was supported by the Medical University of Innsbruck, and partially funded by NIAID contracts No. 75N9301900065, 75N93021C00016, and 75N93019C00051.
Keywords: BNT162b2; ChAdOx1; Heterologous COVID-19 vaccination; Neutralizing antibodies; SARS-CoV-2; T cells.
Conflict of interest statement
The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines which list Florian Krammer as co-inventor. Viviana Simon is also listed on the serological assay patent application as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. Florian Krammer has consulted for Merck and Pfizer (before 2020), and is currently consulting for Pfizer, Seqirus and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. A.S. is a consultant for Gritstone, Flow Pharma, Arcturus, Immunoscape, CellCarta, OxfordImmunotech and Avalia. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work. Dorothee von Laer received fundings from the Medical University of Innsbruck. All other authors declare no conflict of interest.
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
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Source: PubMed