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N Engl J Med . Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming

tetano

Editor, Senior Moderator
N Engl J Med


. 2022 Jan 19.
doi: 10.1056/NEJMoa2116747. Online ahead of print.
Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming


Roos S G Sablerolles[SUP] 1 [/SUP], Wim J R Rietdijk[SUP] 1 [/SUP], Abraham Goorhuis[SUP] 1 [/SUP], Douwe F Postma[SUP] 1 [/SUP], Leo G Visser[SUP] 1 [/SUP], Daryl Geers[SUP] 1 [/SUP], Katharina S Schmitz[SUP] 1 [/SUP], Hannah M Garcia Garrido[SUP] 1 [/SUP], Marion P G Koopmans[SUP] 1 [/SUP], Virgil A S H Dalm[SUP] 1 [/SUP], Neeltje A Kootstra[SUP] 1 [/SUP], Anke L W Huckriede[SUP] 1 [/SUP], Melvin Lafeber[SUP] 1 [/SUP], Debbie van Baarle[SUP] 1 [/SUP], Corine H GeurtsvanKessel[SUP] 1 [/SUP], Rory D de Vries[SUP] 1 [/SUP], P Hugo M van der Kuy[SUP] 1 [/SUP], SWITCH Research Group



Affiliations

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.).
 
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