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

SWITCH Research Group, Roos S G Sablerolles, Wim J R Rietdijk, Abraham Goorhuis, Douwe F Postma, Leo G Visser, Daryl Geers, 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*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

24 Citaten (Scopus)
14 Downloads (Pure)


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 number, NCT04927936.).

Originele taal-2English
Pagina's (van-tot)951-963
Aantal pagina's13
TijdschriftThe New England journal of medicine
Nummer van het tijdschrift10
Vroegere onlinedatum19-jan-2022
StatusPublished - 10-mrt-2022

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