Immunogenicity and reactogenicity of a first booster with BNT162b2 or full-dose mRNA-1273 : a randomised VACCELERATE trial in adults 6575\ua0years (EU-COVAT-1)

Abstract: Background 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. Methods 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 6575 years. Fifty-three participants were randomised to full-doses of either mRNA-1273 (Spikevax\uae, 100 \ub5g) or BNT162b2 (Comirnaty\uae, 30 \ub5g). 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. Results Between 08th of November 2021 and 04th of January 2022, 53 participants 6575 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. Interpretation 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 6575 years