A Bivalent Omicron-Containing Booster Vaccine against Covid-19
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Spyros Chalkias1, Charles Harper1, Keith Vrbicky1
1From Moderna, Cambridge (S.C., N.M., J.E.T., X.C., Y.C., A.S., B.G., D.K.E., J.F., H.Z., J.M.M., R.D.), and Brigham and Women's Hospital, Boston (S.R.W., L.R.B.) - both in Massachusetts; Meridian Clinical Research, Norfolk (C.H., K.V.), Meridian Clinical Research, Omaha (B.E.), and Meridian Clinical Research, Grand Island (A.B.) - all in Nebraska; and the Department of Surgery, Duke University Medical Center, Durham, NC (D.C.M.).
Background:
The safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster vaccine are not known.
Methods:
In this ongoing, phase 2-3 study, we compared the 50-μg bivalent vaccine mRNA-1273.214 (25 μg each of ancestral Wuhan-Hu-1 and omicron B.1.1.529 [BA.1] spike messenger RNAs) with the previously authorized 50-μg mRNA-1273 booster. We administered mRNA-1273.214 or mRNA-1273 as a second booster in adults who had previously received a two-dose (100-μg) primary series and first booster (50-μg) dose of mRNA-1273 (≥3 months earlier). The primary objectives were to assess the safety, reactogenicity, and immunogenicity of mRNA-1273.214 at 28 days after the booster dose.
Results:
Interim results are presented. Sequential groups of participants received 50 μg of mRNA-1273.214 (437 participants) or mRNA-1273 (377 participants) as a second booster dose. The median time between the first and second boosters was similar for mRNA-1273.214 (136 days) and mRNA-1273 (134 days). In participants with no previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the geometric mean titers of neutralizing antibodies against the omicron BA.1 variant were 2372.4 (95% confidence interval [CI], 2070.6 to 2718.2) after receipt of the mRNA-1273.214 booster and 1473.5 (95% CI, 1270.8 to 1708.4) after receipt of the mRNA-1273 booster. In addition, 50-μg mRNA-1273.214 and 50-μg mRNA-1273 elicited geometric mean titers of 727.4 (95% CI, 632.8 to 836.1) and 492.1 (95% CI, 431.1 to 561.9), respectively, against omicron BA.4 and BA.5 (BA.4/5), and the mRNA-1273.214 booster also elicited higher binding antibody responses against multiple other variants (alpha, beta, gamma, and delta) than the mRNA-1273 booster. Safety and reactogenicity were similar with the two booster vaccines. Vaccine effectiveness was not assessed in this study; in an exploratory analysis, SARS-CoV-2 infection occurred in 11 participants after the mRNA-1273.214 booster and in 9 participants after the mRNA-1273 booster.
Conclusions:
The bivalent omicron-containing vaccine mRNA-1273.214 elicited neutralizing antibody responses against omicron that were superior to those with mRNA-1273, without evident safety concerns. (Funded by Moderna; ClinicalTrials.gov number, NCT04927065.).
Insights
The bivalent omicron-containing mRNA-1273.214 vaccine shows superior neutralizing antibody responses against omicron variants compared to the original mRNA-1273 booster. This new vaccine demonstrated similar safety and reactogenicity profiles.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- The safety and immunogenicity of bivalent omicron-containing vaccines remain largely unknown.
- The mRNA-1273.214 vaccine is a bivalent booster candidate containing ancestral Wuhan-Hu-1 and omicron BA.1 spike messenger RNAs.
Purpose of the Study:
- To compare the safety, reactogenicity, and immunogenicity of the bivalent mRNA-1273.214 booster vaccine against the authorized mRNA-1273 booster.
- To assess antibody responses elicited by mRNA-1273.214 in adults who have previously received a primary series and a first booster dose of mRNA-1273.
Main Methods:
- An ongoing phase 2-3 study comparing 50-μg mRNA-1273.214 with 50-μg mRNA-1273 as a second booster dose.
- Participants received boosters at least 3 months after their first booster dose.
- Primary objectives included assessment of safety, reactogenicity, and immunogenicity at 28 days post-booster.
Main Results:
- The mRNA-1273.214 booster elicited significantly higher neutralizing antibody titers against omicron BA.1 and BA.4/5 variants compared to the mRNA-1273 booster.
- Higher binding antibody responses against multiple SARS-CoV-2 variants (alpha, beta, gamma, delta) were observed with mRNA-1273.214.
- Safety and reactogenicity profiles were similar between the bivalent mRNA-1273.214 and the mRNA-1273 booster vaccines.
Conclusions:
- The bivalent omicron-containing mRNA-1273.214 vaccine is superior in eliciting neutralizing antibody responses against omicron variants.
- The mRNA-1273.214 vaccine demonstrates an acceptable safety and reactogenicity profile, comparable to the existing mRNA-1273 booster.
- These findings support the potential of mRNA-1273.214 as an effective booster for enhanced protection against SARS-CoV-2 omicron variants.
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