International Journal of Infectious Diseases (Sep 2024)
Immunogenicity, reactogenicity, and safety of a second booster with BNT162b2 or full-dose mRNA-1273: A randomized VACCELERATE trial in adults aged ≥75 years (EU-COVAT-1-AGED Part B)
- Jannik Stemler,
- Lusine Yeghiazaryan,
- Christoph Stephan,
- Kristin Greve-Isdahl Mohn,
- Antonio-José Carcas-Sansuan,
- Esperanza Romero Rodriguez,
- José Moltó,
- Itziar Vergara Mitxeltorena,
- Tobias Welte,
- Birutė Zablockienė,
- Murat Akova,
- Ullrich Bethe,
- Sarah Heringer,
- Jon Salmanton-García,
- Julia Jeck,
- Lea Tischmann,
- Marouan Zarrouk,
- Arnd Cüppers,
- Lena M. Biehl,
- Jan Grothe,
- Sibylle C. Mellinghoff,
- Julia A. Nacov,
- Julia M. Neuhann,
- Rosanne Sprute,
- Jesús Frías-Iniesta,
- Riya Negi,
- Colette Gaillard,
- Gurvin Saini,
- Alejandro García León,
- Patrick W.G. Mallon,
- Christine Lammens,
- An Hotterbeekx,
- Katherine Loens,
- Surbhi Malhotra-Kumar,
- Herman Goossens,
- Samir Kumar-Singh,
- Franz König,
- Martin Posch,
- Philipp Koehler,
- Oliver A. Cornely
Affiliations
- Jannik Stemler
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany
- Lusine Yeghiazaryan
- Medical University of Vienna, Center for Medical Data Science, Institute of Medical Statistics, Vienna, Austria
- Christoph Stephan
- Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Frankfurt am Main, Germany
- Kristin Greve-Isdahl Mohn
- Helse Bergen HF, Haukeland University Hospital, Department Internal Medicine, Bergen, Norway; Influenza Centre, Department of Clinical Sciences, University of Bergen, Norway
- Antonio-José Carcas-Sansuan
- Hospital La Paz, Clinical Pharmacology Service, Institute for Health Research, Universidad Autónoma de Madrid, Faculty of Medicine, Madrid, Spain
- Esperanza Romero Rodriguez
- Distrito Sanitario Córdoba Guadalquivir, Primary Care Unit, Isla Lanzarote, s/n, Córdoba and Maimonides Biomedical Research Institute of Córdoba(IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
- José Moltó
- Fundació Lluita Contra les Infeccions, Infectious Diseases Department, Hospital Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain
- Itziar Vergara Mitxeltorena
- Asociación Instituto BIODONOSTIA, Primary Care Research Unit of Gipuzkoa Integrated Health Organizations, San Sebastián (Gipuzkoa), Spain
- Tobias Welte
- Medizinische Hochschule Hannover, Klinik für Pneumologie, Hannover, Germany
- Birutė Zablockienė
- Centre of Infectious Diseases, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania; Lithuania and Clinic of Infectious Diseases and Dermatovenerology, Institute of Clinical Medicine, Vilnius University Faculty of Medicine, Vilnius University, Vilnius, Lithuania
- Murat Akova
- Hacettepe University School of Medicine, Department of Infectious Diseases, Ankara, Turkey
- Ullrich Bethe
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany
- Sarah Heringer
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany
- Jon Salmanton-García
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany
- Julia Jeck
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany
- Lea Tischmann
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany
- Marouan Zarrouk
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany
- Arnd Cüppers
- University of Cologne, Faculty of Medicine, Clinical Trials Centre Cologne (CTCC Cologne), Cologne, Germany
- Lena M. Biehl
- 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany
- Jan Grothe
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany
- Sibylle C. Mellinghoff
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany
- Julia A. Nacov
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany
- Julia M. Neuhann
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany
- Rosanne Sprute
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany
- Jesús Frías-Iniesta
- Hospital La Paz, Clinical Pharmacology Service, Institute for Health Research, Universidad Autónoma de Madrid, Faculty of Medicine, Madrid, Spain
- Riya Negi
- Centre for Experimental Pathogen Host Research (CEPHR), School of Medicine, University College Dublin (UCD), Dublin, Ireland
- Colette Gaillard
- Centre for Experimental Pathogen Host Research (CEPHR), School of Medicine, University College Dublin (UCD), Dublin, Ireland
- Gurvin Saini
- Centre for Experimental Pathogen Host Research (CEPHR), School of Medicine, University College Dublin (UCD), Dublin, Ireland
- Alejandro García León
- Centre for Experimental Pathogen Host Research (CEPHR), School of Medicine, University College Dublin (UCD), Dublin, Ireland
- Patrick W.G. Mallon
- Centre for Experimental Pathogen Host Research (CEPHR), School of Medicine, University College Dublin (UCD), Dublin, Ireland
- Christine Lammens
- Laboratory of Medical Microbiology (LMM), Vaccine & Infectious Disease Institute and BioBank Antwerp, University of Antwerp, Antwerpen, Belgium
- An Hotterbeekx
- Molecular Pathology Group, Laboratory of Cell Biology & Histology (CBH) and Vaccine & Infectious Disease Institute (CBH), Faculty of Medicine, University of Antwerp, Antwerpen, Belgium
- Katherine Loens
- Laboratory of Medical Microbiology (LMM), Vaccine & Infectious Disease Institute and BioBank Antwerp, University of Antwerp, Antwerpen, Belgium
- Surbhi Malhotra-Kumar
- Laboratory of Medical Microbiology (LMM), Vaccine & Infectious Disease Institute and BioBank Antwerp, University of Antwerp, Antwerpen, Belgium
- Herman Goossens
- Laboratory of Medical Microbiology (LMM), Vaccine & Infectious Disease Institute and BioBank Antwerp, University of Antwerp, Antwerpen, Belgium
- Samir Kumar-Singh
- Molecular Pathology Group, Laboratory of Cell Biology & Histology (CBH) and Vaccine & Infectious Disease Institute (CBH), Faculty of Medicine, University of Antwerp, Antwerpen, Belgium
- Franz König
- Medical University of Vienna, Center for Medical Data Science, Institute of Medical Statistics, Vienna, Austria
- Martin Posch
- Medical University of Vienna, Center for Medical Data Science, Institute of Medical Statistics, Vienna, Austria
- Philipp Koehler
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany
- Oliver A. Cornely
- University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 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), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn Cologne Department, Cologne, Germany; University of Cologne, Faculty of Medicine, Clinical Trials Centre Cologne (CTCC Cologne), Cologne, Germany; Corresponding author.
- Journal volume & issue
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Vol. 146
p. 107161
Abstract
Objectives: To assess the safety and immunogenicity of a fourth vaccination (second booster) in individuals aged ≥75 years. Methods: Participants were randomized to BNT162b2 (Comirnaty, 30 µg) or messenger RNA (mRNA)-1273 (Spikevax, 100 µg). The primary end point was the rate of two-fold antibody titer increase 14 days after vaccination, targeting the receptor binding domain (RBD) region of wild-type SARS-CoV-2. The secondary end points included changes in neutralizing activity against wild-type and 25 variants. Safety was assessed by monitoring solicited adverse events (AEs) for 7 days. Results: A total of 269 participants (mean age 81 years, mRNA-1273 n = 135/BNT162b2 n = 134) were included. Two-fold anti-RBD immunoglobulin (Ig) G titer increase was achieved by 101 of 129 (78%) and 116 of 133 (87%) subjects in the BNT162b2 and the mRNA-1273 group, respectively (P = 0.054). A second booster of mRNA-1273 provided higher anti-RBD IgG geometric mean titer: 21.326 IU/mL (95% confidence interval: 18.235-24.940) vs BNT162b2: 15.181 IU/mL (95% confidence interval: 13.172-17.497). A higher neutralizing activity was noted for the mRNA-1273 group. The most frequent AE was pain at the injection site (51% in mRNA-1273 and 48% in BNT162b2). Participants in the mRNA-1273 group had less vaccine-related AEs (30% vs 39%). Conclusions: A second booster of either BNT162b2 or mRNA-1273 provided substantial IgG increase. Full-dose mRNA-1273 provided higher IgG levels and neutralizing capacity against SARS-CoV-2, with similar safety profile for subjects of advanced age.
