Immunogenicity, reactogenicity, and safety to assess booster vaccinations with BNT162b2 or double-dose mRNA-1273 in adults ≥75 years (EU-COVAT-1-AGED)–final report

BACKGROUND: To determine long-term immunogenicity and reactogenicity of different SARS-CoV-2 messenger RNA (mRNA) vaccines in a population ≥75 years of age in a randomized trial. METHODS: Participants were randomized to receive either BNT162b2 30 µg or a double booster dose of mRNA-1273, i.e., 100 µg, as the third and fourth vaccinations (first and second booster). The primary endpoint was the rate of a two-fold geometric mean titer (GMT) antibody increase 14 days after vaccination targeting the receptor binding domain (RBD) region of wild-type SARS-CoV-2. Secondary endpoints included neutralizing capacity against wild-type and 25 variants at 14 days (D14) and 12 months (M12). Safety was assessed by monitoring adverse events (AEs) for 7 days after vaccination. FINDINGS: Between November 2021 and September 2022, 322 participants received a SARS-CoV-2 vaccine as a first (Part A) or second booster (Part B). Primary endpoint results have been published previously. In Part A, it was reached by 100% of participants in both vaccine arms, with a higher GMT increase in the mRNA-1273 arm (ratio, 1.64). At M12, the GMT of anti-RBD immunoglobulin G (IgG) was slightly higher than at D14 (9319.7 vs 8568.4 IU/mL) in the BNT162b2 arm, while in the mRNA-1273 arm, the GMT was equal (14,163.8 vs 14,266.7 IU/mL at D14). In Part B, the primary endpoint was reached by 78.5% of participants in the BNT162b2 and 87.2% in the mRNA-1273 arm (P = 0.056), respectively, with a higher GMT increase of anti-RBD IgG for mRNA-1273 (ratio, 1.38). At M12, GMT of anti-RBD IgG was markedly lower than at D14 (9962 vs 15,248.2 IU/mL) in the BNT162b2 arm as well as in the mRNA-1273 arm (12,024.3 vs 21,325.6 IU/mL). Higher neutralizing capacity in individuals who received a booster with mRNA-1273 was detected against wild-type and 15 of 25 tested variants. Fewer participants in the mRNA-1273 arm had vaccine-related AEs (29.6% vs 38.5%), but severity was more frequently grade 2 (n = 38, 28.1% vs n = 22, 16.3%). INTERPRETATION: Long-term serological immunogenicity and virus neutralization capacity in participants ≥75 years of age were numerically better with an mRNA-1273 100 µg booster, with a comparable safety profile.