A Bivalent Omicron-Containing Booster Vaccine against Covid-19,The New England Journal of Medicine

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A Bivalent Omicron-Containing Booster Vaccine against Covid-19
The New England Journal of Medicine ( IF 96.2 ) Pub Date : 2022-09-16 , DOI: 10.1056/nejmoa2208343
Spyros Chalkias ₁ , Charles Harper ₁ , Keith Vrbicky ₁ , Stephen R Walsh ₁ , Brandon Essink ₁ , Adam Brosz ₁ , Nichole McGhee ₁ , Joanne E Tomassini ₁ , Xing Chen ₁ , Ying Chang ₁ , Andrea Sutherland ₁ , David C Montefiori ₁ , Bethany Girard ₁ , Darin K Edwards ₁ , Jing Feng ₁ , Honghong Zhou ₁ , Lindsey R Baden ₁ , Jacqueline M Miller ₁ , Rituparna Das ₁

Affiliation

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.)

中文翻译：

一种针对 Covid-19 的含有 Omicron 的二价加强疫苗

背景

含二价 omicron 的 mRNA-1273.214 加强疫苗的安全性和免疫原性尚不清楚。

方法

在这项正在进行的 2-3 期研究中，我们将 50 μg 二价疫苗 mRNA-1273.214（祖先 Wuu-Hu-1 和 omicron B.1.1.529 [BA.1] 刺突信使 RNA 各 25 μg）与先前授权的 50 μg mRNA-1273 加强剂。我们将 mRNA-1273.214 或 mRNA-1273 作为第二次加强剂给予先前接受过两剂 (100 μg) 初级系列和第一剂 (50 μg) mRNA-1273（≥3 个月前）的成人。主要目标是在加强剂量后 28 天评估 mRNA-1273.214 的安全性、反应原性和免疫原性。

结果

公布了中期结果。连续分组的参与者接受 50 μg mRNA-1273.214（437 名参与者）或 mRNA-1273（377 名参与者）作为第二次加强剂量。mRNA-1273.214（136 天）和 mRNA-1273（134 天）的第一次和第二次加强免疫之间的中位时间相似。在既往没有严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染的参与者中，针对 omicron BA.1 变体的中和抗体的几何平均滴度为 2372.4（95% 置信区间 [CI]，2070.6 至 2718.2）。接受 mRNA-1273.214 加强剂和收到 mRNA-1273 加强剂后的 1473.5（95% CI，1270.8 至 1708.4）。此外，50 μg mRNA-1273.214 和 50 μg mRNA-1273 相对 omicron BA.4 的几何平均滴度分别为 727.4（95% CI，632.8 至 836.1）和 492.1（95% CI，431.1 至 561.9）和 BA.5 (BA.4/5)，并且与 mRNA-1273 加强剂相比，mRNA-1273.214 加强剂还引发了针对多种其他变体（α、β、γ 和 δ）的更高的结合抗体应答。两种加强疫苗的安全性和反应原性相似。本研究未评估疫苗有效性；在一项探索性分析中，在 mRNA-1273.214 加强剂后的 11 名参与者和在 mRNA-1273 加强剂后的 9 名参与者中发生了 SARS-CoV-2 感染。