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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)

Neuhann JM 1 , Stemler J 1 , Carcas AJ 2 , Frías-Iniesta J 2 , Akova M 3 , Bethe U 1 Show all authors , Heringer S 1 , Salmanton-García J 1 , Tischmann L 1 , Zarrouk M 4 , Cüppers A 5 , Grothe J 1 , Leon AG 6 , Mallon P 6 , Negi R 6 , Gaillard C 6 , Saini G 6 , Lammens C 7 , Hotterbeekx A 8 , Loens K 7 , Malhotra-Kumar S 7 , Goossens H 7 , Kumar-Singh S 8 , König F 9 , Yeghiazaryan L 9 , Posch M 9 , Koehler P 10 , Cornely OA 11

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

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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