TY - JOUR
T1 - Heterologous ChAdOx1/BNT162b2 vaccination induces stronger immune response than homologous ChAdOx1 vaccination
T2 - The pragmatic, multi-center, three-arm, partially randomized HEVACC trial
AU - HEVACC Study Group
AU - Bánki, Zoltán
AU - Mateus, Jose
AU - Rössler, Annika
AU - Schäfer, Helena
AU - Bante, David
AU - Riepler, Lydia
AU - Grifoni, Alba
AU - Sette, Alessandro
AU - Simon, Viviana
AU - Falkensammer, Barbara
AU - Ulmer, Hanno
AU - Neurauter, Bianca
AU - Borena, Wegene
AU - Krammer, Florian
AU - von Laer, Dorothee
AU - Weiskopf, Daniela
AU - Kimpel, Janine
N1 - Funding Information:
We thank Sabine Embacher, Albert Falch, Melanie Gössl, Corinna Griesbaum, Julia Haller, Teresa Harthaller, Luiza Hoch, Eva Hochmuth, Maria Huber, Stefan Mayer, Brigitte Müllauer, Michelle Negle, Evelyn Peer, Lisa-Maria Raschbichler, and Lisa Werner for excellent technical and organizational help. We thank Hannes Winner for critical discussion. We gratefully acknowledge the Authors from the Originating laboratories responsible for obtaining the specimens and the Submitting laboratories where genetic sequence data were generated and shared via the GISAID Initiative, on which this research is based (listed in Supplementary Table S12). We are grateful to the Central Institute of Clinical Chemistry and Laboratory Medicine (ZIMCL) of the Medical University of Innsbruck, Hospital Pharmacy of the University Hospital of Innsbruck, the Tirol Kliniken, the city of Innsbruck, the government of the state Tyrol and the ambulance service of Tyrol for technical and organizational support. We thank the Mount Sinai Pathogens Surveillance Program for precision surveillance of SARS-CoV-2 variants circulating in New York City and for access to de-identified, SARS-CoV-2 positive diagnostic nasopharyngeal swab specimen. This work was supported by the Medical University of Innsbruck. This work was partially funded by NIH contract No. 75N9301900065 (DW, AS), contract No. 75N93021C00016 (AS), and by SARS-CoV-2 Assessment of Viral Evolution (SAVE) program to AS. Reagents provided by the Simon and Krammer laboratories were generated using funding from the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. Upon publication of our study, the data will be available from the corresponding authors upon receipt of a suitable request. Aliquots of synthesized sets of peptides utlitzed in this study to characterize vaccine specific T cell responses will be made available upon request to D.W. and execution of a Material transfer agreement. There might be restrictions to the availability of the peptide reagents due to cost and limited quantity.
Funding Information:
This work was supported by the Medical University of Innsbruck. This work was partially funded by NIH contract No. 75N9301900065 (DW, AS), contract No. 75N93021C00016 (AS), and by SARS-CoV-2 Assessment of Viral Evolution (SAVE) program to AS. Reagents provided by the Simon and Krammer laboratories were generated using funding from the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051.
Publisher Copyright:
© 2022 The Authors
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - BNT162b2
KW - ChAdOx1
KW - Heterologous COVID-19 vaccination
KW - Neutralizing antibodies
KW - SARS-CoV-2
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=85131904002&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2022.104073
DO - 10.1016/j.ebiom.2022.104073
M3 - Article
C2 - 35617826
AN - SCOPUS:85131904002
SN - 2352-3964
VL - 80
JO - eBioMedicine
JF - eBioMedicine
M1 - 104073
ER -