2363. Three-Month Safety and Immunogenicity of Bivalent SARS-CoV-2 Omicron-Containing Booster Vaccines: Interim Results From a Phase 3, Randomized, Observer-Blind, Active-Controlled Trial

Abstract Background Updated COVID-19 vaccines have been developed to help broaden protection against circulating SARS-CoV-2 variants. Here we present a 3-month interim analysis from a phase 3, randomized, observer-blind, active-controlled study of 2 omicron BA.1-containing vaccines: BA.1-monovalent mRNA-1273.529 (BA.1 variant only) and BA.1-bivalent mRNA-1273.214 (SARS-CoV-2 Wuhan-Hu-1 strain and BA.1 variant). Methods This multicenter study evaluated safety and immunogenicity of the BA.1-monovalent (Part 1) and -bivalent (Part 2) vaccines in individuals aged ≥ 16 years in the United Kingdom (NCT05249829). Eligible participants previously received 2 or 3 doses of an authorized/approved COVID-19 vaccine and were randomly assigned 1:1 to receive a 50-µg booster of the original mRNA-1273 vaccine or either BA.1-monovalent or -bivalent vaccines. Safety and reactogenicity up to 3 months post-booster were evaluated. Immunogenicity objectives were to demonstrate non-inferiority and/or superiority of BA.1-monovalent or -bivalent vaccine-elicited immune responses to BA.1 and the ancestral strain (D614G) at Day 29 and Month 3 compared with a booster dose of mRNA-1273 in participants without evidence of baseline SARS-CoV-2 infection up to day of analysis visit on Day 29 or Month 3. Results At the interim analysis, 724 (Part 1) and 2824 (Part 2) booster recipients were included in the safety analysis set. BA.1-monovalent and -bivalent booster vaccines were well-tolerated with no new safety concerns identified. Compared with mRNA-1273, a fourth dose of BA.1-monovalent or -bivalent vaccine elicited superior nAb responses against omicron BA.1 at Month 3, with geometric mean ratios (GMRs) of 1.77 (96% CI, 1.55-2.02) and 1.67 (96% CI, 1.54-1.81), respectively. Non-inferior (lower bound of confidence interval ≥ 0.67) nAb responses against D614G were also demonstrated with GMRs of 0.80 (95% CI, 0.71-0.90) for BA.1-monovalent and 1.11 (96% CI, 1.03-1.18) for -bivalent vaccines. Conclusion The BA.1 monovalent and bivalent booster vaccines elicited nAb responses against BA.1 that remain superior to mRNA-1273 at 3 months post-booster with no new safety concerns. These results support variant-updated vaccines to protect against evolving SARS-CoV-2. Disclosures Ivan T. Lee, MD, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Catherine A. Cosgrove, PhD, Novavax: Advisor/Consultant|Novavax: Grant/Research Support|Novavax: Speaker Patrick Moore, MRCGP, AstraZeneca: Advisor/Cons