LB750. Safety and Immunogenicity of a Bivalent Omicron-Containing Booster Vaccine against COVID-19

Abstract

Background Vaccination strategies that provide enhanced immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are needed. We evaluated the safety and immunogenicity of a bivalent omicron containing vaccine, mRNA-1273.214 (50 µg), administered as a second booster dose in adult participants. Methods In this ongoing phase 2/3 trial, 50 µg of the bivalent vaccine mRNA-1273.214 (25 µg each ancestral Wuhan-Hu-1 and omicron BA.1 spike mRNAs) or 50 µg of the authorized mRNA-1273 were administered as second boosters in adults who previously received a 2 dose (100 µg) primary series and a first booster (50 µg) dose of mRNA-1273 (≥ 3 months prior). Primary objectives were safety and reactogenicity and immunogenicity 28 days post-booster dose. Results In participants with no prior SARS-CoV-2 infection who received booster doses of mRNA-1273.214 (n=334) or mRNA-1273 (n=260), neutralizing antibody (nAb) geometric mean titers (GMTs [95% confidence interval (CI)]) against omicron BA.1 were 2372.4 (2070.6−2718.2) and 1473.5 (1270.8−1708.4), respectively. The model-based GMT ratio (GMR [97.5% CI]) of mRNA-1273.214 compared to mRNA-1273 was 1.75 (1.49−2.04), meeting the pre-specified superiority criterion against omicron BA.1. The pre-specified criterion for non-inferiority against the ancestral SARS-CoV-2 strain was also met. Additionally, mRNA-1273.214 elicited higher GMTs (727.4 [632.8−836.1]) than mRNA-1273 (492.1 [431.1−561.9]) against omicron subvariants BA.4/BA.5 [GMR (95% CI) 1.69 [1.51−1.90])]. Binding antibody responses against alpha, beta, gamma, delta, and omicron were numerically higher in the mRNA-1273.214 group compared to mRNA-1273. mRNA-1273.214 GMTs were consistently higher across age (18-< 65 and ≥ 65 years) and pre-booster SARS-CoV-2 infection subgroups (Figure). Safety and reactogenicity were similar for both vaccine groups. Conclusion The bivalent omicron containing mRNA-1273.214 elicited superior nAb responses against omicron 28 days post-immunization compared to mRNA-1273 regardless of age and prior SARS-CoV-2 infection; no new safety concerns were identified. Disclosures Spyros Chalkias, MD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Stephen R. Walsh, MD, Janssen Vaccines: Grant/Research Support|Moderna, Inc.: Grant/Research Support|NIAID/NIH: Grant/Research Support|Sanofi Pasteur: Grant/Research Support Nichole McGhee, B.S., Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Joanne Tomassini, Ph.D., Moderna, Inc.: Advisor/Consultant Xing Chen, Sc.D., Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Ying Chang, M.S., Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Andrea Sutherland, M.D., MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds David Montefiori, Ph.D., Moderna, Inc.: Grant/Research Support Bethany Girard, Ph.D., Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Darin Edwards, Ph.D., Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Jing Feng, M.S., Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Honghong Zhou, Ph.D., Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Lindsey R. Baden, MD, Moderna, Inc.: Grant/Research Support|NIAID: Grant/Research Support Jacqueline Miller, MD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Rituparna Das, M.D., Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds.

Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents

“…Preliminary data from phase II-III trials indicate a boost in neutralizing antibody titers against both XBB.1.5 lineages and BA.2.86. 12 In the most recent real-world data, Marking et al ( 2024) reported a significant increase in neutralization activity against all variants tested after XBB.1.5 vaccination, with a more than 10-fold increase in GMT two weeks after vaccination (84 to 869) in 24 HCWs (median age = 64 years) 14 12 We were encouraged by the finding that a similarly robust GMFR in JN.1 subvariant specific neutralizing antibody to that arising to the XBB.1.5 monovalent vaccination occurred both in NHRs and in HCWs, and both with and without interval infection. However, we also note that absolute JN.1 specific neutralizing antibody titers after XBB.1.5 monovalent vaccination were far below those of XBB specific neutralizing titers after XBB.1.5 monovalent vaccination.…”

“…Preliminary data from phase II-III trials indicate a boost in neutralizing antibody titers against both XBB.1.5 lineages and BA.2.86. 12 In the most recent real-world data, Marking et al (2024) reported a significant increase in neutralization activity against all variants tested after XBB.1.5 vaccination, with a more than 10-fold increase in GMT two weeks after vaccination (84 to 869) in 24 HCWs (median age = 64 years) 14 and Stankov et al (2024) reported a rise in GMT neutralization from 27 to 967 for XBB.1.5 and from 28 to 906 for XBB.1.16 after the updated monovalent Omicron XBB.1.5 vaccine (median age = 45). 13 Our study cohort demonstrated 13.6 GMFR (from 88 to 1198) in neutralizing antibodies to XBB.1.5 in HCWs, 11.3 GMFR (from 49 to 555) in NH without known SARS-CoV-2 infection since bivalent vaccine dose, and 17.3 GMFR (from 121 to 2089) in NHRs with known interval infection.…”

“…Previously, Chalkias et al (2023) reported similar GMFRs of neutralizing antibody levels in ancestral, BA.4/5 and XBB.1.5 sub variants after monovalent XBB.1.5 vaccine in a relatively younger study population (n=50, median age 55). 12…”

“…[7][8][9] The first and second monovalent boost and bivalent SARS-CoV-2 mRNA vaccine augmented immunity and demonstrated significant reduction in risk of infection, hospitalization and death at four months following vaccine administration. 10,11 The newer monovalent XBB.1.5 vaccine has demonstrated adequate immunogenicity and cross-reactivity with current circulating strains in healthier, younger populations, [12][13][14] but it is unknown whether this broader protection is also afforded to NHRs. We present an assessment of the immune response following XBB.1.5 monovalent vaccination to prior SARS-CoV-2 strains and the JN.1 variant among NHRs and a reference population of HCWs.…”