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; EU-COVAT-1 AGED study group on behalf of the VACCELERATE consortium

doi:10.1016/j.ijid.2024.107161

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)

Int J Infect Dis. 2024 Sep:146:107161. doi: 10.1016/j.ijid.2024.107161. Epub 2024 Jul 9.

Authors

Jannik Stemler¹, Lusine Yeghiazaryan², Christoph Stephan³, Kristin Greve-Isdahl Mohn⁴, Antonio-José Carcas-Sansuan⁵, Esperanza Romero Rodriguez⁶, José Moltó⁷, Itziar Vergara Mitxeltorena⁸, Tobias Welte⁹, Birutė Zablockienė¹⁰, Murat Akova¹¹, Ullrich Bethe¹, Sarah Heringer¹, Jon Salmanton-García¹, Julia Jeck¹, Lea Tischmann¹, Marouan Zarrouk¹², Arnd Cüppers¹³, Lena M Biehl¹⁴, Jan Grothe¹, Sibylle C Mellinghoff¹, Julia A Nacov¹, Julia M Neuhann¹, Rosanne Sprute¹, Jesús Frías-Iniesta⁵, Riya Negi¹⁵, Colette Gaillard¹⁵, Gurvin Saini¹⁵, Alejandro García León¹⁵, Patrick W G Mallon¹⁵, Christine Lammens¹⁶, An Hotterbeekx¹⁷, Katherine Loens¹⁶, Surbhi Malhotra-Kumar¹⁶, Herman Goossens¹⁶, Samir Kumar-Singh¹⁷, Franz König², Martin Posch², Philipp Koehler¹⁸, Oliver A Cornely¹⁹; EU-COVAT-1 AGED study group on behalf of the VACCELERATE consortium

Affiliations

¹ 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.
² Medical University of Vienna, Center for Medical Data Science, Institute of Medical Statistics, Vienna, Austria.
³ Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Frankfurt am Main, Germany.
⁴ Helse Bergen HF, Haukeland University Hospital, Department Internal Medicine, Bergen, Norway; Influenza Centre, Department of Clinical Sciences, University of Bergen, Norway.
⁵ Hospital La Paz, Clinical Pharmacology Service, Institute for Health Research, Universidad Autónoma de Madrid, Faculty of Medicine, Madrid, Spain.
⁶ 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.
⁷ Fundació Lluita Contra les Infeccions, Infectious Diseases Department, Hospital Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain; CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain.
⁸ Asociación Instituto BIODONOSTIA, Primary Care Research Unit of Gipuzkoa Integrated Health Organizations, San Sebastián (Gipuzkoa), Spain.
⁹ Medizinische Hochschule Hannover, Klinik für Pneumologie, Hannover, Germany.
¹⁰ 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.
¹¹ Hacettepe University School of Medicine, Department of Infectious Diseases, Ankara, Turkey.
¹² University of Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
¹³ University of Cologne, Faculty of Medicine, Clinical Trials Centre Cologne (CTCC Cologne), Cologne, Germany.
¹⁴ 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.
¹⁵ Centre for Experimental Pathogen Host Research (CEPHR), School of Medicine, University College Dublin (UCD), Dublin, Ireland.
¹⁶ Laboratory of Medical Microbiology (LMM), Vaccine & Infectious Disease Institute and BioBank Antwerp, University of Antwerp, Antwerpen, Belgium.
¹⁷ Molecular Pathology Group, Laboratory of Cell Biology & Histology (CBH) and Vaccine & Infectious Disease Institute (CBH), Faculty of Medicine, University of Antwerp, Antwerpen, Belgium.
¹⁸ 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.
¹⁹ 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. Electronic address: [email protected].

PMID: 38992789
DOI: 10.1016/j.ijid.2024.107161

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.

Keywords: Advanced age; Booster vaccination; Immunosenescence; Neutralizing antibodies; SARS-CoV-2; Variants of concern.

Publication types

Randomized Controlled Trial

MeSH terms

2019-nCoV Vaccine mRNA-1273* / immunology
Aged
Aged, 80 and over
Antibodies, Neutralizing* / blood
Antibodies, Viral* / blood
BNT162 Vaccine* / immunology
COVID-19 Vaccines / administration & dosage
COVID-19 Vaccines / adverse effects
COVID-19 Vaccines / immunology
COVID-19* / immunology
COVID-19* / prevention & control
Female
Humans
Immunization, Secondary*
Immunogenicity, Vaccine*
Immunoglobulin G / blood
Male
SARS-CoV-2* / immunology
Spike Glycoprotein, Coronavirus / immunology

Substances

BNT162 Vaccine
Antibodies, Viral
2019-nCoV Vaccine mRNA-1273
Antibodies, Neutralizing
COVID-19 Vaccines
Immunoglobulin G
Spike Glycoprotein, Coronavirus

Supplementary concepts

SARS-CoV-2 variants