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)

• Published in: Vaccine 2023-11, Vol.41 (48), p.7166-7175
• Main Authors: Neuhann, Julia M., Stemler, Jannik, Carcas, Antonio J., Frías-Iniesta, Jesús, Akova, Murat, Bethe, Ullrich, Heringer, Sarah, Salmanton-García, Jon, Tischmann, Lea, Zarrouk, Marouan, Cüppers, Arnd, Grothe, Jan, Leon, Alejandro Garcia, Mallon, Patrick, Negi, Riya, Gaillard, Colette, Saini, Gurvin, Lammens, Christine, Hotterbeekx, An, Loens, Katherine, Malhotra-Kumar, Surbhi, Goossens, Herman, Kumar-Singh, Samir, König, Franz, Yeghiazaryan, Lusine, Posch, Martin, Koehler, Philipp, Cornely, Oliver A.
• Format: Article
• Language: English
• Subjects: 2019-nCoV Vaccine mRNA-1273; Adult; Advanced age; Age; Aged; Anti-RBD IgG; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; BNT162 Vaccine; Confidence intervals; COVID-19; COVID-19 vaccines; COVID-19 Vaccines - adverse effects; Dosage; Electrochemiluminescence; Humans; Immunoassay; Immunogenicity; Immunogenicity, Vaccine; Immunoglobulin G; Immunoglobulins; mRNA; Neutralising antibodies; Regulatory approval; RNA, Messenger; Safety; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Third dose; Variants of concern
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2023.10.029

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. 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. 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. 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. This trial was funded by the European Commission (Framework Program HORIZON 2020).