Heterologous ChAdOx1/BNT162b2 vaccination induces stronger immune response than homologous ChAdOx1 vaccination: The pragmatic, multi-center, three-arm, partially randomized HEVACC trial.
BNT162b2
ChAdOx1
Heterologous COVID-19 vaccination
Neutralizing antibodies
SARS-CoV-2
T cells
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
25
10
2021
revised:
27
04
2022
accepted:
06
05
2022
pubmed:
27
5
2022
medline:
15
6
2022
entrez:
26
5
2022
Statut:
ppublish
Résumé
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. 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. 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. This study clearly shows the immunogenicity and safety of heterologous AZ/BNT vaccination and encourages further studies on heterologous vaccination schedules. This work was supported by the Medical University of Innsbruck, and partially funded by NIAID contracts No. 75N9301900065, 75N93021C00016, and 75N93019C00051.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
CONCLUSIONS
This study clearly shows the immunogenicity and safety of heterologous AZ/BNT vaccination and encourages further studies on heterologous vaccination schedules.
FUNDING
BACKGROUND
This work was supported by the Medical University of Innsbruck, and partially funded by NIAID contracts No. 75N9301900065, 75N93021C00016, and 75N93019C00051.
Identifiants
pubmed: 35617826
pii: S2352-3964(22)00254-7
doi: 10.1016/j.ebiom.2022.104073
pmc: PMC9126042
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
COVID-19 Vaccines
0
Vaccines, Synthetic
0
mRNA Vaccines
0
BNT162 Vaccine
N38TVC63NU
Banques de données
ClinicalTrials.gov
['NCT04907331']
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
104073Investigateurs
Petra Flatscher
(P)
Lukas Forer
(L)
Elisabeth Graf
(E)
Gerhard Hausberger
(G)
Peter Heininger
(P)
Michael Kundi
(M)
Christine Mantinger
(C)
Conny Ower
(C)
Daniel Rainer
(D)
Magdalena Sacher
(M)
Lisa Seekircher
(L)
Sebastian Schönherr
(S)
Marton Szell
(M)
Tobias Trips
(T)
Ursula Wiedermann
(U)
Peter Willeit
(P)
Reinhard Würzner
(R)
August Zabernigg
(A)
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Références
N Engl J Med. 2021 Jun 10;384(23):2187-2201
pubmed: 33882225
Vaccines (Basel). 2021 Aug 04;9(8):
pubmed: 34451982
Cell. 2020 Jun 25;181(7):1489-1501.e15
pubmed: 32473127
Lancet Infect Dis. 2021 Sep;21(9):1212-1213
pubmed: 34332707
Cell Host Microbe. 2021 Apr 14;29(4):516-521.e3
pubmed: 33798491
Nat Med. 2021 Sep;27(9):1530-1535
pubmed: 34312554
Science. 2020 Oct 2;370(6512):89-94
pubmed: 32753554
J Immunol Res. 2015;2015:763461
pubmed: 26568965
Lancet. 2021 May 29;397(10289):2043-2046
pubmed: 33991480
J Virol. 2007 May;81(10):4928-40
pubmed: 17329346
Lancet. 2021 Mar 6;397(10277):881-891
pubmed: 33617777
N Engl J Med. 2022 May 5;386(18):1764-1766
pubmed: 35320661
Lancet Respir Med. 2021 Nov;9(11):1255-1265
pubmed: 34391547
Methods Protoc. 2018 Jan 22;1(1):
pubmed: 31164554
Expert Rev Vaccines. 2019 Aug;18(8):765-779
pubmed: 31271322
Cell Rep Med. 2021 Jul 20;2(7):100355
pubmed: 34230917
Cell. 2020 Nov 12;183(4):996-1012.e19
pubmed: 33010815
Nature. 2022 Feb;602(7898):654-656
pubmed: 35016196
Nature. 2022 Feb;602(7898):682-688
pubmed: 35016197
Therapie. 2021 Jul-Aug;76(4):369-373
pubmed: 34083026
Nat Med. 2022 Mar;28(3):496-503
pubmed: 35090165
N Engl J Med. 2021 Jun 17;384(24):2352-2354
pubmed: 33826819
N Engl J Med. 2022 Apr 21;386(16):1532-1546
pubmed: 35249272
Cell Mol Immunol. 2021 Oct;18(10):2455-2456
pubmed: 34426672
Lancet. 2021 Jul 10;398(10295):121-130
pubmed: 34181880
Science. 2021 Oct 22;374(6566):eabj9853
pubmed: 34519540
N Engl J Med. 2021 Nov 4;385(19):1761-1773
pubmed: 34525277
Lancet. 2021 Sep 4;398(10303):856-869
pubmed: 34370971
Cell. 2022 Mar 3;185(5):847-859.e11
pubmed: 35139340
N Engl J Med. 2022 Feb 17;386(7):698-700
pubmed: 35021005
Science. 2021 Feb 5;371(6529):
pubmed: 33408181
Vaccines (Basel). 2020 Dec 28;9(1):
pubmed: 33379160
Nature. 2022 Mar;603(7901):488-492
pubmed: 35102311
Cell. 2021 Apr 29;184(9):2523
pubmed: 33930298
N Engl J Med. 2021 Aug 12;385(7):585-594
pubmed: 34289274
EBioMedicine. 2021 Nov;73:103626
pubmed: 34688034
Nat Med. 2021 Sep;27(9):1525-1529
pubmed: 34262158
Nat Commun. 2021 May 17;12(1):2893
pubmed: 34001897