Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming

Roos S G Sablerolles; Abraham Goorhuis; SWITCH Research Group; Wim J R Rietdijk; Douwe F Postma; Leo G Visser; Daryl Geers; Katharina S Schmitz; Hannah M Garcia Garrido; Marion P G Koopmans; Virgil A S H Dalm; Neeltje A Kootstra; Anke L W Huckriede; Melvin Lafeber; Debbie van Baarle; Corine H GeurtsvanKessel; Rory D de Vries; P Hugo M van der Kuy

doi:10.1056/NEJMoa2116747

Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming

Roos S G Sablerolles, Abraham Goorhuis, SWITCH Research Group, Wim J R Rietdijk, Douwe F Postma, Leo G Visser, Daryl Geers, Katharina S Schmitz, Hannah M Garcia Garrido, Marion P G Koopmans, Virgil A S H Dalm, Neeltje A Kootstra, Anke L W Huckriede, Melvin Lafeber, Debbie van Baarle, Corine H GeurtsvanKessel, Rory D de Vries, P Hugo M van der Kuy

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND: The Ad26.COV2.S vaccine, which was approved as a single-shot immunization regimen, has been shown to be effective against severe coronavirus disease 2019. However, this vaccine induces lower severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S)-specific antibody levels than those induced by messenger RNA (mRNA)-based vaccines. The immunogenicity and reactogenicity of a homologous or heterologous booster in persons who have received an Ad26.COV2.S priming dose are unclear.

METHODS: In this single-blind, multicenter, randomized, controlled trial involving health care workers who had received a priming dose of Ad26.COV2.S vaccine, we assessed immunogenicity and reactogenicity 28 days after a homologous or heterologous booster vaccination. The participants were assigned to receive no booster, an Ad26.COV2.S booster, an mRNA-1273 booster, or a BNT162b2 booster. The primary end point was the level of S-specific binding antibodies, and the secondary end points were the levels of neutralizing antibodies, S-specific T-cell responses, and reactogenicity. A post hoc analysis was performed to compare mRNA-1273 boosting with BNT162b2 boosting.

RESULTS: Homologous or heterologous booster vaccination in 434 participants resulted in higher levels of S-specific binding antibodies, neutralizing antibodies, and T-cell responses than a single Ad26.COV2.S vaccination. The increase in binding antibodies was significantly larger with heterologous regimens that included mRNA-based vaccines than with the homologous booster. The mRNA-1273 booster was most immunogenic and was associated with higher reactogenicity than the BNT162b2 and Ad26.COV2.S boosters. Local and systemic reactions were generally mild to moderate in the first 2 days after booster administration.

CONCLUSIONS: The Ad26.COV2.S and mRNA boosters had an acceptable safety profile and were immunogenic in health care workers who had received a priming dose of Ad26.COV2.S vaccine. The strongest responses occurred after boosting with mRNA-based vaccines. Boosting with any available vaccine was better than not boosting. (Funded by the Netherlands Organization for Health Research and Development ZonMw; SWITCH ClinicalTrials.gov number, NCT04927936.).

Original language	English
Pages (from-to)	951-963
Number of pages	13
Journal	New England Journal of Medicine
Volume	386
Issue number	10
Early online date	19 Jan 2022
DOIs	https://doi.org/10.1056/NEJMoa2116747
Publication status	Published - 10 Mar 2022

Bibliographical note

Funding Information:
Supported by a grant (10430072110001) from the Netherlands Organization for Health Research and Development ZonMw. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

Publisher Copyright:
Copyright © 2022 Massachusetts Medical Society.

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https://hdl.handle.net/11370/a2a830f0-ff54-4ac5-9c1d-bab0044a09b1Licence: Article 25fa Dutch Copyright Act

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Sablerolles, R. S. G., Goorhuis, A., SWITCH Research Group, Rietdijk, W. J. R., Postma, D. F., Visser, L. G., Geers, D., Schmitz, K. S., Garcia Garrido, H. M., Koopmans, M. P. G., Dalm, V. A. S. H., Kootstra, N. A., Huckriede, A. L. W., Lafeber, M., van Baarle, D., GeurtsvanKessel, C. H., de Vries, R. D., & van der Kuy, P. H. M. (2022). Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming. New England Journal of Medicine, 386(10), 951-963. https://doi.org/10.1056/NEJMoa2116747

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title = "Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming",

abstract = "BACKGROUND: The Ad26.COV2.S vaccine, which was approved as a single-shot immunization regimen, has been shown to be effective against severe coronavirus disease 2019. However, this vaccine induces lower severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S)-specific antibody levels than those induced by messenger RNA (mRNA)-based vaccines. The immunogenicity and reactogenicity of a homologous or heterologous booster in persons who have received an Ad26.COV2.S priming dose are unclear.METHODS: In this single-blind, multicenter, randomized, controlled trial involving health care workers who had received a priming dose of Ad26.COV2.S vaccine, we assessed immunogenicity and reactogenicity 28 days after a homologous or heterologous booster vaccination. The participants were assigned to receive no booster, an Ad26.COV2.S booster, an mRNA-1273 booster, or a BNT162b2 booster. The primary end point was the level of S-specific binding antibodies, and the secondary end points were the levels of neutralizing antibodies, S-specific T-cell responses, and reactogenicity. A post hoc analysis was performed to compare mRNA-1273 boosting with BNT162b2 boosting.RESULTS: Homologous or heterologous booster vaccination in 434 participants resulted in higher levels of S-specific binding antibodies, neutralizing antibodies, and T-cell responses than a single Ad26.COV2.S vaccination. The increase in binding antibodies was significantly larger with heterologous regimens that included mRNA-based vaccines than with the homologous booster. The mRNA-1273 booster was most immunogenic and was associated with higher reactogenicity than the BNT162b2 and Ad26.COV2.S boosters. Local and systemic reactions were generally mild to moderate in the first 2 days after booster administration.CONCLUSIONS: The Ad26.COV2.S and mRNA boosters had an acceptable safety profile and were immunogenic in health care workers who had received a priming dose of Ad26.COV2.S vaccine. The strongest responses occurred after boosting with mRNA-based vaccines. Boosting with any available vaccine was better than not boosting. (Funded by the Netherlands Organization for Health Research and Development ZonMw; SWITCH ClinicalTrials.gov number, NCT04927936.).",

author = "Sablerolles, {Roos S G} and Abraham Goorhuis and {SWITCH Research Group} and Rietdijk, {Wim J R} and Postma, {Douwe F} and Visser, {Leo G} and Daryl Geers and Schmitz, {Katharina S} and {Garcia Garrido}, {Hannah M} and Koopmans, {Marion P G} and Dalm, {Virgil A S H} and Kootstra, {Neeltje A} and Huckriede, {Anke L W} and Melvin Lafeber and {van Baarle}, Debbie and GeurtsvanKessel, {Corine H} and {de Vries}, {Rory D} and {van der Kuy}, {P Hugo M}",

note = "Funding Information: Supported by a grant (10430072110001) from the Netherlands Organization for Health Research and Development ZonMw. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. Publisher Copyright: Copyright {\textcopyright} 2022 Massachusetts Medical Society.",

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month = mar,

day = "10",

doi = "10.1056/NEJMoa2116747",

language = "English",

volume = "386",

pages = "951--963",

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Sablerolles, RSG, Goorhuis, A, SWITCH Research Group, Rietdijk, WJR, Postma, DF, Visser, LG, Geers, D , Schmitz, KS, Garcia Garrido, HM, Koopmans, MPG, Dalm, VASH, Kootstra, NA, Huckriede, ALW, Lafeber, M, van Baarle, D, GeurtsvanKessel, CH , de Vries, RD & van der Kuy, PHM 2022, 'Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming', New England Journal of Medicine, vol. 386, no. 10, pp. 951-963. https://doi.org/10.1056/NEJMoa2116747

TY - JOUR

T1 - Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming

AU - Sablerolles, Roos S G

AU - Goorhuis, Abraham

AU - SWITCH Research Group

AU - Rietdijk, Wim J R

AU - Postma, Douwe F

AU - Visser, Leo G

AU - Geers, Daryl

AU - Schmitz, Katharina S

AU - Garcia Garrido, Hannah M

AU - Koopmans, Marion P G

AU - Dalm, Virgil A S H

AU - Kootstra, Neeltje A

AU - Huckriede, Anke L W

AU - Lafeber, Melvin

AU - van Baarle, Debbie

AU - GeurtsvanKessel, Corine H

AU - de Vries, Rory D

AU - van der Kuy, P Hugo M

N1 - Funding Information: Supported by a grant (10430072110001) from the Netherlands Organization for Health Research and Development ZonMw. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. Publisher Copyright: Copyright © 2022 Massachusetts Medical Society.

PY - 2022/3/10

Y1 - 2022/3/10

N2 - BACKGROUND: The Ad26.COV2.S vaccine, which was approved as a single-shot immunization regimen, has been shown to be effective against severe coronavirus disease 2019. However, this vaccine induces lower severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S)-specific antibody levels than those induced by messenger RNA (mRNA)-based vaccines. The immunogenicity and reactogenicity of a homologous or heterologous booster in persons who have received an Ad26.COV2.S priming dose are unclear.METHODS: In this single-blind, multicenter, randomized, controlled trial involving health care workers who had received a priming dose of Ad26.COV2.S vaccine, we assessed immunogenicity and reactogenicity 28 days after a homologous or heterologous booster vaccination. The participants were assigned to receive no booster, an Ad26.COV2.S booster, an mRNA-1273 booster, or a BNT162b2 booster. The primary end point was the level of S-specific binding antibodies, and the secondary end points were the levels of neutralizing antibodies, S-specific T-cell responses, and reactogenicity. A post hoc analysis was performed to compare mRNA-1273 boosting with BNT162b2 boosting.RESULTS: Homologous or heterologous booster vaccination in 434 participants resulted in higher levels of S-specific binding antibodies, neutralizing antibodies, and T-cell responses than a single Ad26.COV2.S vaccination. The increase in binding antibodies was significantly larger with heterologous regimens that included mRNA-based vaccines than with the homologous booster. The mRNA-1273 booster was most immunogenic and was associated with higher reactogenicity than the BNT162b2 and Ad26.COV2.S boosters. Local and systemic reactions were generally mild to moderate in the first 2 days after booster administration.CONCLUSIONS: The Ad26.COV2.S and mRNA boosters had an acceptable safety profile and were immunogenic in health care workers who had received a priming dose of Ad26.COV2.S vaccine. The strongest responses occurred after boosting with mRNA-based vaccines. Boosting with any available vaccine was better than not boosting. (Funded by the Netherlands Organization for Health Research and Development ZonMw; SWITCH ClinicalTrials.gov number, NCT04927936.).

AB - BACKGROUND: The Ad26.COV2.S vaccine, which was approved as a single-shot immunization regimen, has been shown to be effective against severe coronavirus disease 2019. However, this vaccine induces lower severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S)-specific antibody levels than those induced by messenger RNA (mRNA)-based vaccines. The immunogenicity and reactogenicity of a homologous or heterologous booster in persons who have received an Ad26.COV2.S priming dose are unclear.METHODS: In this single-blind, multicenter, randomized, controlled trial involving health care workers who had received a priming dose of Ad26.COV2.S vaccine, we assessed immunogenicity and reactogenicity 28 days after a homologous or heterologous booster vaccination. The participants were assigned to receive no booster, an Ad26.COV2.S booster, an mRNA-1273 booster, or a BNT162b2 booster. The primary end point was the level of S-specific binding antibodies, and the secondary end points were the levels of neutralizing antibodies, S-specific T-cell responses, and reactogenicity. A post hoc analysis was performed to compare mRNA-1273 boosting with BNT162b2 boosting.RESULTS: Homologous or heterologous booster vaccination in 434 participants resulted in higher levels of S-specific binding antibodies, neutralizing antibodies, and T-cell responses than a single Ad26.COV2.S vaccination. The increase in binding antibodies was significantly larger with heterologous regimens that included mRNA-based vaccines than with the homologous booster. The mRNA-1273 booster was most immunogenic and was associated with higher reactogenicity than the BNT162b2 and Ad26.COV2.S boosters. Local and systemic reactions were generally mild to moderate in the first 2 days after booster administration.CONCLUSIONS: The Ad26.COV2.S and mRNA boosters had an acceptable safety profile and were immunogenic in health care workers who had received a priming dose of Ad26.COV2.S vaccine. The strongest responses occurred after boosting with mRNA-based vaccines. Boosting with any available vaccine was better than not boosting. (Funded by the Netherlands Organization for Health Research and Development ZonMw; SWITCH ClinicalTrials.gov number, NCT04927936.).

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DO - 10.1056/NEJMoa2116747

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Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming

Abstract

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