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).

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.
Competing Interests: Declarations of competing interest JS has received research grants by the German Federal Ministry of Education and Research (BMBF), Noscendo and Basilea Pharmaceuticals; has received speaker honoraria by AbbVie, Hikma, 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, all outside the submitted work. 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. JSG has received speaker honoraria from Gilead and Pfizer, outside of the submitted work. MZ has received honoraria for lecturing courses by Pfizer Malaysia; is now an employee with AiCuris AG. RS has received lecture honoraria from Pfizer and Hikma, outside of the submitted work. 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 collaborations from AbbVie. PWGM has received honoraria and/or grant funding from Gilead, Janssen, MSD, ViiV Healthcare, GSK, and AstraZeneca, outside of the submitted work. SMK has received grants from Pfizer, MSD, Huvepharma, AiCuris, Astra Zeneca, Mylan, Janssen pharma. 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 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, and The Prime Meridian Group. Kristin G-I Mohn has received honoraria for lectures from Takeda, IQVIA and BioNTech, has received a Research Grant from Norwegian Regional Health authorities, West, grant nr F12626 and is a Member of an advisory board on committee for National vaccination programs, Norwegian Public Health Institute. The remaining authors have no competing interest to declare.
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