PortalPublikationenSafety, reactogenicity, and immunogenicity of homologous and...

Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study

Standard

Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study. / Hillus, David; Schwarz, Tatjana; Tober-Lau, Pinkus; Vanshylla, Kanika; Hastor, Hana; Thibeault, Charlotte; Jentzsch, Stefanie; Helbig, Elisa T; Lippert, Lena J; Tscheak, Patricia; Schmidt, Marie Luisa; Riege, Johanna; Solarek, André; von Kalle, Christof; Dang-Heine, Chantip; Gruell, Henning; Kopankiewicz, Piotr; Suttorp, Norbert; Drosten, Christian; Bias, Harald; Seybold, Joachim; Klein, Florian; Kurth, Florian; Corman, Victor Max; Sander, Leif Erik; EICOV/COVIM Study Group.

in: LANCET RESP MED, Jahrgang 9, Nr. 11, 11.2021, S. 1255-1265.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Hillus, D, Schwarz, T, Tober-Lau, P, Vanshylla, K, Hastor, H, Thibeault, C, Jentzsch, S, Helbig, ET, Lippert, LJ, Tscheak, P, Schmidt, ML, Riege, J, Solarek, A, von Kalle, C, Dang-Heine, C, Gruell, H, Kopankiewicz, P, Suttorp, N, Drosten, C, Bias, H, Seybold, J, Klein, F, Kurth, F, Corman, VM, Sander, LE & EICOV/COVIM Study Group 2021, 'Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study', LANCET RESP MED, Jg. 9, Nr. 11, S. 1255-1265. https://doi.org/10.1016/S2213-2600(21)00357-X

APA

Hillus, D., Schwarz, T., Tober-Lau, P., Vanshylla, K., Hastor, H., Thibeault, C., Jentzsch, S., Helbig, E. T., Lippert, L. J., Tscheak, P., Schmidt, M. L., Riege, J., Solarek, A., von Kalle, C., Dang-Heine, C., Gruell, H., Kopankiewicz, P., Suttorp, N., Drosten, C., ... EICOV/COVIM Study Group (2021). Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study. LANCET RESP MED, 9(11), 1255-1265. https://doi.org/10.1016/S2213-2600(21)00357-X

Vancouver

Hillus D, Schwarz T, Tober-Lau P, Vanshylla K, Hastor H, Thibeault C et al. Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study. LANCET RESP MED. 2021 Nov;9(11):1255-1265. https://doi.org/10.1016/S2213-2600(21)00357-X

Bibtex

@article{fa4cbf137e2042e9a5c56d6d8901a17e,
title = "Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study",
abstract = "BACKGROUND: Heterologous vaccine regimens have been widely discussed as a way to mitigate intermittent supply shortages and to improve immunogenicity and safety of COVID-19 vaccines. We aimed to assess the reactogenicity and immunogenicity of heterologous immunisations with ChAdOx1 nCov-19 (AstraZeneca, Cambridge, UK) and BNT162b2 (Pfizer-BioNtech, Mainz, Germany) compared with homologous BNT162b2 and ChAdOx1 nCov-19 immunisation.METHODS: This is an interim analysis of a prospective observational cohort study enrolling health-care workers in Berlin (Germany) who received either homologous ChAdOx1 nCov-19 or heterologous ChAdOx1 nCov-19-BNT162b2 vaccination with a 10-12-week vaccine interval or homologous BNT162b2 vaccination with a 3-week vaccine interval. We assessed reactogenicity after the first and second vaccination by use of electronic questionnaires on days 1, 3, 5, and 7. Immunogenicity was measured by the presence of SARS-CoV-2-specific antibodies (full spike-IgG, S1-IgG, and RBD-IgG), by an RBD-ACE2 binding inhibition assay (surrogate SARS-CoV-2 virus neutralisation test), a pseudovirus neutralisation assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351]), and anti-S1-IgG avidity. T-cell reactivity was measured by IFN-γ release assay.FINDINGS: Between Dec 27, 2020, and June 14, 2021, 380 participants were enrolled in the study, with 174 receiving homologous BNT162b2 vaccination, 38 receiving homologous ChAdOx1 nCov-19 vaccination, and 104 receiving ChAdOx1 nCov-19-BNT162b2 vaccination. Systemic symptoms were reported by 103 (65%, 95% CI 57·1-71·8) of 159 recipients of homologous BNT162b2, 14 (39%, 24·8-55·1) of 36 recipients of homologous ChAdOx1 nCov-19, and 51 (49%, 39·6-58·5) of 104 recipients of ChAdOx1 nCov-19-BNT162b2 after the booster immunisation. Median anti-RBD IgG levels 3 weeks after boost immunisation were 5·4 signal to cutoff ratio (S/co; IQR 4·8-5·9) in recipients of homologous BNT162b2, 4·9 S/co (4·3-5·6) in recipients of homologous ChAdOx1 nCov-19, and 5·6 S/co (5·1-6·1) in recipients of ChAdOx1 nCov-19- BNT162b2. Geometric mean of 50% inhibitory dose against alpha and beta variants were highest in recipients of ChAdOx1 nCov-19-BNT162b2 (956·6, 95% CI 835·6-1095, against alpha and 417·1, 349·3-498·2, against beta) compared with those in recipients of homologous ChAdOx1 nCov-19 (212·5, 131·2-344·4, against alpha and 48·5, 28·4-82·8, against beta; both p<0·0001) or homologous BNT162b2 (369·2, 310·7-438·6, against alpha and 72·4, 60·5-86·5, against beta; both p<0·0001). SARS-CoV-2 S1 T-cell reactivity 3 weeks after boost immunisation was highest in recipients of ChAdOx1 nCov-19-BNT162b2 (median IFN-γ concentration 4762 mIU/mL, IQR 2723-8403) compared with that in recipients of homologous ChAdOx1 nCov-19 (1061 mIU/mL, 599-2274, p<0·0001) and homologous BNT162b2 (2026 mIU/mL, 1459-4621, p=0·0008) vaccination.INTERPRETATION: The heterologous ChAdOx1 nCov-19-BNT162b2 immunisation with 10-12-week interval, recommended in Germany, is well tolerated and improves immunogenicity compared with homologous ChAdOx1 nCov-19 vaccination with 10-12-week interval and BNT162b2 vaccination with 3-week interval. Heterologous prime-boost immunisation strategies for COVID-19 might be generally applicable.FUNDING: Forschungsnetzwerk der Universit{\"a}tsmedizin zu COVID-19, the German Ministry of Education and Research, Zalando SE.",
keywords = "Antibodies, Viral/blood, BNT162 Vaccine/immunology, COVID-19/prevention & control, ChAdOx1 nCoV-19/immunology, Germany, Health Personnel, Humans, Immunogenicity, Vaccine, Immunoglobulin G/blood, Neutralization Tests, Prospective Studies, SARS-CoV-2, Vaccination",
author = "David Hillus and Tatjana Schwarz and Pinkus Tober-Lau and Kanika Vanshylla and Hana Hastor and Charlotte Thibeault and Stefanie Jentzsch and Helbig, {Elisa T} and Lippert, {Lena J} and Patricia Tscheak and Schmidt, {Marie Luisa} and Johanna Riege and Andr{\'e} Solarek and {von Kalle}, Christof and Chantip Dang-Heine and Henning Gruell and Piotr Kopankiewicz and Norbert Suttorp and Christian Drosten and Harald Bias and Joachim Seybold and Florian Klein and Florian Kurth and Corman, {Victor Max} and Sander, {Leif Erik} and {EICOV/COVIM Study Group}",
note = "Copyright {\textcopyright} 2021 Elsevier Ltd. All rights reserved.",
year = "2021",
month = nov,
doi = "10.1016/S2213-2600(21)00357-X",
language = "English",
volume = "9",
pages = "1255--1265",
journal = "LANCET RESP MED",
issn = "2213-2600",
publisher = "Elsevier Limited",
number = "11",

}

RIS

TY - JOUR

T1 - Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study

AU - Hillus, David

AU - Schwarz, Tatjana

AU - Tober-Lau, Pinkus

AU - Vanshylla, Kanika

AU - Hastor, Hana

AU - Thibeault, Charlotte

AU - Jentzsch, Stefanie

AU - Helbig, Elisa T

AU - Lippert, Lena J

AU - Tscheak, Patricia

AU - Schmidt, Marie Luisa

AU - Riege, Johanna

AU - Solarek, André

AU - von Kalle, Christof

AU - Dang-Heine, Chantip

AU - Gruell, Henning

AU - Kopankiewicz, Piotr

AU - Suttorp, Norbert

AU - Drosten, Christian

AU - Bias, Harald

AU - Seybold, Joachim

AU - Klein, Florian

AU - Kurth, Florian

AU - Corman, Victor Max

AU - Sander, Leif Erik

AU - EICOV/COVIM Study Group

N1 - Copyright © 2021 Elsevier Ltd. All rights reserved.

PY - 2021/11

Y1 - 2021/11

N2 - BACKGROUND: Heterologous vaccine regimens have been widely discussed as a way to mitigate intermittent supply shortages and to improve immunogenicity and safety of COVID-19 vaccines. We aimed to assess the reactogenicity and immunogenicity of heterologous immunisations with ChAdOx1 nCov-19 (AstraZeneca, Cambridge, UK) and BNT162b2 (Pfizer-BioNtech, Mainz, Germany) compared with homologous BNT162b2 and ChAdOx1 nCov-19 immunisation.METHODS: This is an interim analysis of a prospective observational cohort study enrolling health-care workers in Berlin (Germany) who received either homologous ChAdOx1 nCov-19 or heterologous ChAdOx1 nCov-19-BNT162b2 vaccination with a 10-12-week vaccine interval or homologous BNT162b2 vaccination with a 3-week vaccine interval. We assessed reactogenicity after the first and second vaccination by use of electronic questionnaires on days 1, 3, 5, and 7. Immunogenicity was measured by the presence of SARS-CoV-2-specific antibodies (full spike-IgG, S1-IgG, and RBD-IgG), by an RBD-ACE2 binding inhibition assay (surrogate SARS-CoV-2 virus neutralisation test), a pseudovirus neutralisation assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351]), and anti-S1-IgG avidity. T-cell reactivity was measured by IFN-γ release assay.FINDINGS: Between Dec 27, 2020, and June 14, 2021, 380 participants were enrolled in the study, with 174 receiving homologous BNT162b2 vaccination, 38 receiving homologous ChAdOx1 nCov-19 vaccination, and 104 receiving ChAdOx1 nCov-19-BNT162b2 vaccination. Systemic symptoms were reported by 103 (65%, 95% CI 57·1-71·8) of 159 recipients of homologous BNT162b2, 14 (39%, 24·8-55·1) of 36 recipients of homologous ChAdOx1 nCov-19, and 51 (49%, 39·6-58·5) of 104 recipients of ChAdOx1 nCov-19-BNT162b2 after the booster immunisation. Median anti-RBD IgG levels 3 weeks after boost immunisation were 5·4 signal to cutoff ratio (S/co; IQR 4·8-5·9) in recipients of homologous BNT162b2, 4·9 S/co (4·3-5·6) in recipients of homologous ChAdOx1 nCov-19, and 5·6 S/co (5·1-6·1) in recipients of ChAdOx1 nCov-19- BNT162b2. Geometric mean of 50% inhibitory dose against alpha and beta variants were highest in recipients of ChAdOx1 nCov-19-BNT162b2 (956·6, 95% CI 835·6-1095, against alpha and 417·1, 349·3-498·2, against beta) compared with those in recipients of homologous ChAdOx1 nCov-19 (212·5, 131·2-344·4, against alpha and 48·5, 28·4-82·8, against beta; both p<0·0001) or homologous BNT162b2 (369·2, 310·7-438·6, against alpha and 72·4, 60·5-86·5, against beta; both p<0·0001). SARS-CoV-2 S1 T-cell reactivity 3 weeks after boost immunisation was highest in recipients of ChAdOx1 nCov-19-BNT162b2 (median IFN-γ concentration 4762 mIU/mL, IQR 2723-8403) compared with that in recipients of homologous ChAdOx1 nCov-19 (1061 mIU/mL, 599-2274, p<0·0001) and homologous BNT162b2 (2026 mIU/mL, 1459-4621, p=0·0008) vaccination.INTERPRETATION: The heterologous ChAdOx1 nCov-19-BNT162b2 immunisation with 10-12-week interval, recommended in Germany, is well tolerated and improves immunogenicity compared with homologous ChAdOx1 nCov-19 vaccination with 10-12-week interval and BNT162b2 vaccination with 3-week interval. Heterologous prime-boost immunisation strategies for COVID-19 might be generally applicable.FUNDING: Forschungsnetzwerk der Universitätsmedizin zu COVID-19, the German Ministry of Education and Research, Zalando SE.

AB - BACKGROUND: Heterologous vaccine regimens have been widely discussed as a way to mitigate intermittent supply shortages and to improve immunogenicity and safety of COVID-19 vaccines. We aimed to assess the reactogenicity and immunogenicity of heterologous immunisations with ChAdOx1 nCov-19 (AstraZeneca, Cambridge, UK) and BNT162b2 (Pfizer-BioNtech, Mainz, Germany) compared with homologous BNT162b2 and ChAdOx1 nCov-19 immunisation.METHODS: This is an interim analysis of a prospective observational cohort study enrolling health-care workers in Berlin (Germany) who received either homologous ChAdOx1 nCov-19 or heterologous ChAdOx1 nCov-19-BNT162b2 vaccination with a 10-12-week vaccine interval or homologous BNT162b2 vaccination with a 3-week vaccine interval. We assessed reactogenicity after the first and second vaccination by use of electronic questionnaires on days 1, 3, 5, and 7. Immunogenicity was measured by the presence of SARS-CoV-2-specific antibodies (full spike-IgG, S1-IgG, and RBD-IgG), by an RBD-ACE2 binding inhibition assay (surrogate SARS-CoV-2 virus neutralisation test), a pseudovirus neutralisation assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351]), and anti-S1-IgG avidity. T-cell reactivity was measured by IFN-γ release assay.FINDINGS: Between Dec 27, 2020, and June 14, 2021, 380 participants were enrolled in the study, with 174 receiving homologous BNT162b2 vaccination, 38 receiving homologous ChAdOx1 nCov-19 vaccination, and 104 receiving ChAdOx1 nCov-19-BNT162b2 vaccination. Systemic symptoms were reported by 103 (65%, 95% CI 57·1-71·8) of 159 recipients of homologous BNT162b2, 14 (39%, 24·8-55·1) of 36 recipients of homologous ChAdOx1 nCov-19, and 51 (49%, 39·6-58·5) of 104 recipients of ChAdOx1 nCov-19-BNT162b2 after the booster immunisation. Median anti-RBD IgG levels 3 weeks after boost immunisation were 5·4 signal to cutoff ratio (S/co; IQR 4·8-5·9) in recipients of homologous BNT162b2, 4·9 S/co (4·3-5·6) in recipients of homologous ChAdOx1 nCov-19, and 5·6 S/co (5·1-6·1) in recipients of ChAdOx1 nCov-19- BNT162b2. Geometric mean of 50% inhibitory dose against alpha and beta variants were highest in recipients of ChAdOx1 nCov-19-BNT162b2 (956·6, 95% CI 835·6-1095, against alpha and 417·1, 349·3-498·2, against beta) compared with those in recipients of homologous ChAdOx1 nCov-19 (212·5, 131·2-344·4, against alpha and 48·5, 28·4-82·8, against beta; both p<0·0001) or homologous BNT162b2 (369·2, 310·7-438·6, against alpha and 72·4, 60·5-86·5, against beta; both p<0·0001). SARS-CoV-2 S1 T-cell reactivity 3 weeks after boost immunisation was highest in recipients of ChAdOx1 nCov-19-BNT162b2 (median IFN-γ concentration 4762 mIU/mL, IQR 2723-8403) compared with that in recipients of homologous ChAdOx1 nCov-19 (1061 mIU/mL, 599-2274, p<0·0001) and homologous BNT162b2 (2026 mIU/mL, 1459-4621, p=0·0008) vaccination.INTERPRETATION: The heterologous ChAdOx1 nCov-19-BNT162b2 immunisation with 10-12-week interval, recommended in Germany, is well tolerated and improves immunogenicity compared with homologous ChAdOx1 nCov-19 vaccination with 10-12-week interval and BNT162b2 vaccination with 3-week interval. Heterologous prime-boost immunisation strategies for COVID-19 might be generally applicable.FUNDING: Forschungsnetzwerk der Universitätsmedizin zu COVID-19, the German Ministry of Education and Research, Zalando SE.

KW - Antibodies, Viral/blood

KW - BNT162 Vaccine/immunology

KW - COVID-19/prevention & control

KW - ChAdOx1 nCoV-19/immunology

KW - Germany

KW - Health Personnel

KW - Humans

KW - Immunogenicity, Vaccine

KW - Immunoglobulin G/blood

KW - Neutralization Tests

KW - Prospective Studies

KW - SARS-CoV-2

KW - Vaccination

U2 - 10.1016/S2213-2600(21)00357-X

DO - 10.1016/S2213-2600(21)00357-X

M3 - SCORING: Journal article

C2 - 34391547

VL - 9

SP - 1255

EP - 1265

JO - LANCET RESP MED

JF - LANCET RESP MED

SN - 2213-2600

IS - 11

ER -