• Roos S G Sablerolles, Wim J R Rietdijk, Abraham Goorhuis, Douwe F Postma, Leo G Visser, Daryl Geers, Katharina S Schmitz, Hannah M Garcia Garrido, KoopmansMarion P GMPGFrom the Departments of Internal Medicine (R.S.G.S., M.L.), Hospital Pharmacy (R.S.G.S., W.J.R.R., P.H.M.K.), and Viroscience (D.G., K.S.S., M.P.G.K., C.H.G., R.D.V.) and the Department of Internal Medicine, Division of Allergy and Cl, Virgil A S H Dalm, Neeltje A Kootstra, Anke L W Huckriede, Melvin Lafeber, Debbie van Baarle, Corine H GeurtsvanKessel, Rory D de Vries, van der KuyP Hugo MPHM0000-0002-7128-8801From the Departments of Internal Medicine (R.S.G.S., M.L.), Hospital Pharmacy (R.S.G.S., W.J.R.R., P.H.M.K.), and Viroscience (D.G., K.S.S., M.P.G.K., C.H.G., R.D.V.) and the Department of Internal Medicine, Divisi, and SWITCH Research Group.
• From the Departments of Internal Medicine (R.S.G.S., M.L.), Hospital Pharmacy (R.S.G.S., W.J.R.R., P.H.M.K.), and Viroscience (D.G., K.S.S., M.P.G.K., C.H.G., R.D.V.) and the Department of Internal Medicine, Division of Allergy and Clinical Immunology, and Department of Immunology (V.A.S.H.D.), Erasmus University Medical Center, Rotterdam, the Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases (A.G., H.M.G.G.), and the Department of Experimental Immunology, Amsterdam University Medical Centers, Amsterdam Institute for Infection and Immunity, University of Amsterdam (N.A.K.), Amsterdam, the Department of Internal Medicine and Infectious Diseases (D.F.P.), and the Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen (A.L.W.H., D.B.), Groningen, the Department of Infectious Diseases, Leiden University Medical Center, Leiden (L.G.V.), and the Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven (D.B.) - all in the Netherlands.
• N. Engl. J. Med. 2022 Mar 10; 386 (10): 951963951-963.

BackgroundThe 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.MethodsIn 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.ResultsHomologous or heterologous booster vaccination 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.ConclusionsThe 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.).Copyright © 2022 Massachusetts Medical Society.

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