Immunogenicity, Reactogenicity and Safety of a Second Booster with BNT162b2 or Full-Dose mRNA-1273: A Randomised VACCELERATE Trial in Adults ≥75 Years (EU-COVAT-1-AGED Part B)

• DOI: 10.2139/ssrn.4671824
• Publication Date: 2023-12-22T18:55:19Z
• Authors: Jannik Stemler; Lusine Yeghiazaryan; Christoph Stephan; Kirsten Greve-Isd...; Antonio J Carcas; Esperanza Romero ...; José Marhuenda Moltó; Itziar Vergara Mi...; Tobias Welte; Birutė Zablockienė; Murat Akova; Ullrich Bethe; Sarah Heringer; Jon Salmanton-Garcia; Julia Jeck; Lea Tischmann; Marouan Zarrouk; Arnd Cüppers; Lena M. Biehl; Jan H. Grothe; Sibylle Mellinghoff; Julia Alexandra ...; Julia M. Neuhann; Rosanne Sprute; Jesús Frías; Riya Negi; Colette Gaillard; Gurvin Saini; Alejandro Abner G...; Patrick Mallon; Christine Lammens; An Hotterbeekx; Katherine Loens; Surbhi Malhotra-K...; Herman Goossens; Samir Kumar-Singh; Franz König; Martin Posch; Philipp Koehler; Oliver A. Cornely
• Keywords: Reactogenicity; Booster (rocketry); Booster dose

Background: Booster vaccination for the elderly provides protection from severe SARS-CoV-2 infection, however data is still limited on optimal timing, dosing and immunogenicity in this population.Methods: EU-COVAT-1-AGED Part B a randomised controlled, adaptive, multicentre, phase II trial evaluating safety of 4th (2nd booster) individuals ≥75 years. Participants were to receive either BNT162b2 (Comirnaty®, 30µg) or mRNA-1273 (Spikevax®, 100µg). The primary endpoint was rate 2-fold antibody titre increase 14 days post-vaccination targeting receptor binding domain (RBD) region wild-type SARS-CoV-2. Secondary endpoints included changes neutralising capacity against 25 variants at days. Safety assessed by monitoring solicited adverse events (AE) seven after vaccination.Findings: Between February September 2022, 270 participants aged years received vaccine as 2nd booster. A total 269 (mRNA-1273 n=135/BNT162b2 n=134) analysis. anti-RBD IgG achieved 101/129 (78%) subjects group 116/133 (87%) (p=0.054). booster full-dose provided higher titres per geometric mean titre: 21.326 IU/mL (95%-CI: 18.235; 24.940) vs. BNT162b2: 15.181 13172; 17497). Higher well 15 out tested detected. most frequent AE both arms pain injection site (51% 48% BNT162b2). number with vaccine-related AEs lower than (30% 39%), but severity more frequently rated grade 2 (n=34, 25% n=21, 16%).Interpretation: substantial circulating vaccination. Full-dose levels an overall similar profile ≥ 75 years.Trial Registration: ClinicalTrials.gov Identifier: NCT05160766, EudraCT Number: 2021-004526-29.Funding: This funded European Commission (Framework Program HORIZON 2020 VACCELERATE Grant Agreement No. 101037867).Declaration Interest: JS has research grants German Federal Ministry Education Research (BMBF), Noscendo Basilea Pharmaceuticals; speaker honoraria AbbVie, Hikma, Pfizer Gilead; been consultant Gilead, Produkt&Markt GmbH, Alvea Vax Micron travel Society Infectious Diseases (DGI) Meta-Alexander Foundation, all outside submitted work. MA Gilead. Contributed educational activities organized/supported Pfizer, Roche, GSK, Moderna Sanofi. All these are paid Institution. JSG Gilead MZ lecturing courses Malaysia; now employee AiCuris AG. RS lecture JFI Instituto de Salud Carlos III, Science. Spain. Has contracts Laboratorios Faes, Normon, Italfarmaco, Prestige, Cinfa, Mundipharma, Abbott, Novartis docency colaborations Abbvie. PWGM and/or grant funding Janssen, MSD, ViiV Healthcare, GSK AstraZeneca, SMK Huvepharma, AiCuris, Astra Zeneca, Mylan, Janssen pharma. PK reports (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung) NAPKON (Nationales Pandemie Kohorten Netz, National Pandemic Cohort Network) Network University Medicine (NUM) State North Rhine-Westphalia; Consulting fees Ambu Sciences, Mundipharma Resarch Limited, Noxxon N.V. Pharma; Honoraria lectures Akademie für Infektionsmedizin e.V., Astellas Pharma, BioRad Laboratories Inc., Datamed Confederation Medical Mycology, GPR Academy Ruesselsheim, HELIOS Kliniken Lahn-Dill-Kliniken medupdate MedMedia MSD Sharp & Dohme Pharma Scilink Comunicación Científica SC, streamedup! GmbH Hospital LMU Munich; Participation Advisory Board Limited pending patent currently reviewed Patent Trade Mark Office (DE 10 2021 113 007.7); Other non-financial interests Elsevier, Wiley Taylor Francis online OAC Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Matinas, MedPace, Octapharma, Scynexis; Abbvie, Biocon, Biosys, Da Volterra, IQVIA, Menarini, Molecular Partners, MSG-ERC, Noxxon, PSI, Scynexis, Seres; Al- Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, MedScape, MedUpdate, Merck/MSD, Noscendo, Shionogi; Payment expert testimony Cidara; Data Monitoring Actelion, Allecra, Entasis, Paratek, Pulmocide, Shionogi, Prime Meridian Group. Remaining authors no conflicts declared.Ethical Approval: approved Ethics Committee Faculty Medicine, Cologne, Germany (Identifier: 21-1457-AMG-ff) ethics committees participating sites. written informed consent before start participation.