Immunogenicity and reactogenicity of a first booster with BNT162b2 or full-dose mRNA-1273: A randomised VACCELERATE trial in adults ≥75 years (EU-COVAT-1)

Julia M Neuhann¹, Jannik Stemler¹, Antonio J Carcas², Jesús Frías-Iniesta², Murat Akova³, Ullrich Bethe¹, Sarah Heringer¹, Jon Salmanton-García¹, Lea Tischmann¹, Marouan Zarrouk⁴, Arnd Cüppers⁵, Jan Grothe¹, Alejandro Garcia Leon⁶, Patrick Mallon⁶, Riya Negi⁶, Colette Gaillard⁶, Gurvin Saini⁶, Christine Lammens⁷, An Hotterbeekx⁸, Katherine Loens⁷, Surbhi Malhotra-Kumar⁷, Herman Goossens⁷, Samir Kumar-Singh⁸, Franz König⁹, Lusine Yeghiazaryan⁹, Martin Posch⁹, Philipp Koehler¹⁰, Oliver A Cornely¹¹

Affiliations

¹ University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Herderstr. 52, 50931 Cologne, Germany; University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Kerpener Str. 62, 50937 Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne Department, Herderstr. 52, 50931 Cologne, Germany.
² Hospital La Paz, Clinical Pharmacology Service, Institute for Health Research (IdiPAZ), Universidad Autónoma de Madrid, Faculty of Medicine, Madrid, Spain.
³ Hacettepe University School of Medicine, Department of Infectious Diseases, Ankara, Turkey.
⁴ University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Herderstr. 52, 50931 Cologne, Germany.
⁵ University of Cologne, Faculty of Medicine, Clinical Trials Centre Cologne (CTCC Cologne), Gleueler Str. 269, 50935 Cologne, Germany.
⁶ Centre for Experimental Pathogen Host Research (CEPHR), School of Medicine, University College Dublin (UCD), Ireland.
⁷ Laboratory of Medical Microbiology (LMM), Vaccine & Infectious Disease Institute and Biobank Antwerp, University of Antwerp, Belgium.
⁸ Molecular Pathology Group, Laboratory of Cell Biology & Histology and Vaccine & Infectious Disease Institute (CBH), Faculty of Medicine, University of Antwerp, Belgium.
⁹ Medical University of Vienna, Center for Medical Data Science, Spitalgasse 23, 1090 Vienna, Austria.
¹⁰ University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Herderstr. 52, 50931 Cologne, Germany; University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Kerpener Str. 62, 50937 Cologne, Germany.
¹¹ University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Herderstr. 52, 50931 Cologne, Germany; University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Kerpener Str. 62, 50937 Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne Department, Herderstr. 52, 50931 Cologne, Germany; University of Cologne, Faculty of Medicine, Clinical Trials Centre Cologne (CTCC Cologne), Gleueler Str. 269, 50935 Cologne, Germany. Electronic address: oliver.cornely@uk-koeln.de.

PMID: 37919141
DOI: 10.1016/j.vaccine.2023.10.029

Clinical Trial

Immunogenicity and reactogenicity of a first booster with BNT162b2 or full-dose mRNA-1273: A randomised VACCELERATE trial in adults ≥75 years (EU-COVAT-1)

Julia M Neuhann et al. Vaccine. 2023.

. 2023 Nov 22;41(48):7166-7175.

doi: 10.1016/j.vaccine.2023.10.029. Epub 2023 Oct 31.

Authors

Affiliations

¹ University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Herderstr. 52, 50931 Cologne, Germany; University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Kerpener Str. 62, 50937 Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne Department, Herderstr. 52, 50931 Cologne, Germany.
² Hospital La Paz, Clinical Pharmacology Service, Institute for Health Research (IdiPAZ), Universidad Autónoma de Madrid, Faculty of Medicine, Madrid, Spain.
³ Hacettepe University School of Medicine, Department of Infectious Diseases, Ankara, Turkey.
⁴ University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Herderstr. 52, 50931 Cologne, Germany.
⁵ University of Cologne, Faculty of Medicine, Clinical Trials Centre Cologne (CTCC Cologne), Gleueler Str. 269, 50935 Cologne, Germany.
⁶ Centre for Experimental Pathogen Host Research (CEPHR), School of Medicine, University College Dublin (UCD), Ireland.
⁷ Laboratory of Medical Microbiology (LMM), Vaccine & Infectious Disease Institute and Biobank Antwerp, University of Antwerp, Belgium.
⁸ Molecular Pathology Group, Laboratory of Cell Biology & Histology and Vaccine & Infectious Disease Institute (CBH), Faculty of Medicine, University of Antwerp, Belgium.
⁹ Medical University of Vienna, Center for Medical Data Science, Spitalgasse 23, 1090 Vienna, Austria.
¹⁰ University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Herderstr. 52, 50931 Cologne, Germany; University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Kerpener Str. 62, 50937 Cologne, Germany.
¹¹ University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Herderstr. 52, 50931 Cologne, Germany; University of Cologne, Faculty of Medicine, and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Kerpener Str. 62, 50937 Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne Department, Herderstr. 52, 50931 Cologne, Germany; University of Cologne, Faculty of Medicine, Clinical Trials Centre Cologne (CTCC Cologne), Gleueler Str. 269, 50935 Cologne, Germany. Electronic address: oliver.cornely@uk-koeln.de.

PMID: 37919141
DOI: 10.1016/j.vaccine.2023.10.029

Abstract

Background: Vaccination remains crucial for protection against severe SARS-CoV-2 infection, especially for people of advanced age, however, optimal dosing regimens are as yet lacking.

Methods: EU-COVAT-1-AGED Part A is a randomised controlled, adaptive, multicentre phase II trial evaluating safety and immunogenicity of a 3rd vaccination (1st booster) in individuals ≥75 years. Fifty-three participants were randomised to full-doses of either mRNA-1273 (Spikevax®, 100 µg) or BNT162b2 (Comirnaty®, 30 µg). The primary endpoint was the rate of 2-fold circulating antibody titre increase 14 days post-vaccination measured by quantitative electrochemiluminescence (ECL) immunoassay, targeting RBD region of Wuhan wild-type SARS-CoV-2. Secondary endpoints included the changes in neutralising capacity against wild-type and 25 variants of concern at 14 days and up to 12 months. Safety was assessed by monitoring of solicited adverse events (AEs) for seven days after on-study vaccination. Unsolicited AEs were collected until the end of follow-up at 12 months, SAEs were pursued for a further 30 days.

Results: Between 08th of November 2021 and 04th of January 2022, 53 participants ≥75 years received a COVID-19 vaccine as 1st booster. Fifty subjects (BNT162b2 n = 25/mRNA-1273 n = 25) were included in the analyses for immunogenicity at day 14. The primary endpoint of a 2-fold anti-RBD IgG titre increase 14 days after vaccination was reached for all subjects. A 3rd vaccination of full-dose mRNA-1273 provided higher anti-RBD IgG titres (Geometric mean titre) D14 mRNA-127310711 IU/mL (95 %-CI: 8003;14336) vs. BNT162b2: 7090 IU/mL (95 %-CI: 5688;8837). We detected a pattern showing higher neutralising capacity of full-dose mRNA-1273 against wild-type as well as for 23 out of 25 tested variants.

Interpretation: Third doses of either BNT162b2 or mRNA-1273 provide substantial circulating antibody increase 14 days after vaccination. Full-dose mRNA-1273 provides higher antibody levels with an overall similar safety profile for people ≥75 years.

Funding: This trial was funded by the European Commission (Framework Program HORIZON 2020).

Keywords: Advanced age; Anti-RBD IgG; Neutralising antibodies; SARS-CoV-2; Third dose; Variants of concern.

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Conflict of interest statement

Declaration of Competing Interest JN no conflicts declared. JS has received research grants by the Ministry of Education and Research (BMBF) and Basilea Pharmaceuticals; has received speaker honoraria by AbbVie, Pfizer and Gilead; has been a consultant to Gilead, Produkt & Markt GmbH, Alvea Vax and Micron Research and has received travel grants by German Society for Infectious Diseases (DGI) and Meta-Alexander Foundation. AJC no conflicts declared. JFI has received research grants by the Instituto de Salud Carlos III, Ministry of Science. Spain. Has received grants or research contracts from Laboratorios Faes, Normon, Pfizer, Italfarmaco, GSK, Prestige, has been a consultant or has received speaker honoraria from Faes, Normon, Cinfa, Mundipharma, Abbott, Novartis and docency colaborations from Abbvie. MA has received research grants from Pfizer and Gilead. Contributed to educational activities organized/supported by Pfizer, Roche, Gilead, GSK, Moderna and Sanofi. All honoraria from these activities are paid to the Institution. UB no conflicts declared. SH no conflicts declared. JSG has received speaker honoraria from Gilead and Pfizer, outside of the submitted work. LT no conflicts declared. MZ has received honoraria for lecturing courses by Pfizer Malaysia; is now an employee with AiCuris AG. AC no conflicts declared. JG no conflicts declared. AGL no conflicts declared. PM has received honoraria from Gilead and AstraZeneca, outside of the submitted work. RN no conflicts declared. CG no conflicts declared. GS no conflicts declared. AH no conflicts declared. SKS no conflicts declared. KL no conflicts declared. CL no conflicts declared. HG no conflicts declared. SMK has received grants from Pfizer, MSD, Huvepharma, AiCuris, Astra Zeneca, Mylan, Janssen pharma. FK no conflicts declared. LY no conflicts declared. MP no conflicts declared. PK reports grants or contracts from German Federal Ministry of Research and Education (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung) and NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network) of the Network University Medicine (NUM) and the State of North Rhine-Westphalia; Consulting fees Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited, Noxxon N.V. and Pfizer Pharma; Honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., Datamed GmbH, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, HELIOS Kliniken GmbH, Lahn-Dill-Kliniken GmbH, medupdate GmbH, MedMedia GmbH, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC, streamedup! GmbH and University Hospital and LMU Munich; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited and Pfizer Pharma; A pending patent currently reviewed at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. OAC reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Abbvie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, Pfizer, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Abbvie, Al-Jazeera Pharmaceuticals, Astellas, Gilead, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Noscendo, Pfizer, Shionogi; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, PSI, Pulmocide, Shionogi, The Prime Meridian Group; A patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Stocks from CoRe Consulting, EasyRadiology; Other interests from DGHO, DGI, ECMM, EHA, ISHAM, MSG-ERC, Wiley.

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Immunogenicity and reactogenicity of a first booster with BNT162b2 or full-dose mRNA-1273: A randomised VACCELERATE trial in adults ≥75 years (EU-COVAT-1)

Affiliations

Immunogenicity and reactogenicity of a first booster with BNT162b2 or full-dose mRNA-1273: A randomised VACCELERATE trial in adults ≥75 years (EU-COVAT-1)

Authors

Affiliations

Abstract

Conflict of interest statement

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