tetano
Editor, Senior Moderator
N Engl J Med
. 2022 Sep 16.
doi: 10.1056/NEJMoa2208343. Online ahead of print.
A Bivalent Omicron-Containing Booster Vaccine against Covid-19
Spyros Chalkias[SUP] 1 [/SUP], Charles Harper[SUP] 1 [/SUP], Keith Vrbicky[SUP] 1 [/SUP], Stephen R Walsh[SUP] 1 [/SUP], Brandon Essink[SUP] 1 [/SUP], Adam Brosz[SUP] 1 [/SUP], Nichole McGhee[SUP] 1 [/SUP], Joanne E Tomassini[SUP] 1 [/SUP], Xing Chen[SUP] 1 [/SUP], Ying Chang[SUP] 1 [/SUP], Andrea Sutherland[SUP] 1 [/SUP], David C Montefiori[SUP] 1 [/SUP], Bethany Girard[SUP] 1 [/SUP], Darin K Edwards[SUP] 1 [/SUP], Jing Feng[SUP] 1 [/SUP], Honghong Zhou[SUP] 1 [/SUP], Lindsey R Baden[SUP] 1 [/SUP], Jacqueline M Miller[SUP] 1 [/SUP], Rituparna Das[SUP] 1 [/SUP]
Affiliations
Abstract
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.).
. 2022 Sep 16.
doi: 10.1056/NEJMoa2208343. Online ahead of print.
A Bivalent Omicron-Containing Booster Vaccine against Covid-19
Spyros Chalkias[SUP] 1 [/SUP], Charles Harper[SUP] 1 [/SUP], Keith Vrbicky[SUP] 1 [/SUP], Stephen R Walsh[SUP] 1 [/SUP], Brandon Essink[SUP] 1 [/SUP], Adam Brosz[SUP] 1 [/SUP], Nichole McGhee[SUP] 1 [/SUP], Joanne E Tomassini[SUP] 1 [/SUP], Xing Chen[SUP] 1 [/SUP], Ying Chang[SUP] 1 [/SUP], Andrea Sutherland[SUP] 1 [/SUP], David C Montefiori[SUP] 1 [/SUP], Bethany Girard[SUP] 1 [/SUP], Darin K Edwards[SUP] 1 [/SUP], Jing Feng[SUP] 1 [/SUP], Honghong Zhou[SUP] 1 [/SUP], Lindsey R Baden[SUP] 1 [/SUP], Jacqueline M Miller[SUP] 1 [/SUP], Rituparna Das[SUP] 1 [/SUP]
Affiliations
- PMID: 36112399
- DOI: 10.1056/NEJMoa2208343
Abstract
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.).