Moderna, Inc., Cambridge, MA, USA.
Meridian Clinical Research, Binghamton, NY, USA.
Nat Med. 2022 Nov;28(11):2388-2397. doi: 10.1038/s41591-022-02031-7. Epub 2022 Oct 6.
Updated immunization strategies are needed to address multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here we report interim results from an ongoing, open-label phase 2/3 trial evaluating the safety and immunogenicity of the bivalent Coronavirus Disease 2019 (COVID-19) vaccine candidate mRNA-1273.211, which contains equal mRNA amounts encoding the ancestral SARS-CoV-2 and Beta variant spike proteins, as 50-µg (n = 300) and 100-µg (n = 595) first booster doses administered approximately 8.7-9.7 months after the mRNA-1273 primary vaccine series ( NCT04927065 ). The primary objectives were to evaluate the safety and reactogenicity of mRNA-1273.211 and to demonstrate non-inferior antibody responses compared to the mRNA-1273 100-µg primary series. Additionally, a pre-specified immunogenicity objective was to demonstrate superior antibody responses compared to the previously authorized mRNA-1273 50-µg booster. The mRNA-1273.211 booster doses (50-µg or 100-µg) 28 days after immunization elicited higher neutralizing antibody responses against the ancestral SARS-CoV-2 and Beta variant than those elicited 28 days after the second mRNA‑1273 dose of the primary series ( NCT04470427 ). Antibody responses 28 days and 180 days after the 50-µg mRNA-1273.211 booster dose were also higher than those after a 50-µg mRNA-1273 booster dose ( NCT04405076 ) against the ancestral SARS-CoV-2 and Beta, Omicron BA.1 and Delta variants, and all pre-specified immunogenicity objectives were met. The safety and reactogenicity profile of the bivalent mRNA-1273.211 booster (50-µg) was similar to the booster dose of mRNA-1273 (50-µg). Immunization with the primary series does not set a ceiling to the neutralizing antibody response, and a booster dose of the bivalent vaccine elicits a robust response with titers that are likely to be protective against COVID-19. These results indicate that bivalent booster vaccines can induce potent, durable and broad antibody responses against multiple variants, providing a new tool in response to emerging variants.
需要更新免疫策略以应对多种严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 变体。在这里，我们报告了一项正在进行的、开放性标签的 2/3 期试验的中期结果，该试验评估了二价新型冠状病毒病 (COVID-19) 疫苗候选物 mRNA-1273.211 的安全性和免疫原性，该疫苗包含等量的编码原始 SARS-CoV-2 和 Beta 变体刺突蛋白的 mRNA，作为约 8.7-9.7 个月后 mRNA-1273 初级疫苗系列（NCT04927065）的 50-µg（n=300）和 100-µg（n=595）首剂加强针。主要目的是评估 mRNA-1273.211 的安全性和反应原性，并证明与 mRNA-1273 100-µg 初级系列相比具有非劣效抗体反应。此外，一个预先指定的免疫原性目标是证明与先前批准的 mRNA-1273 50-µg 加强针相比具有更好的抗体反应。接种 mRNA-1273.211 加强针（50-µg 或 100-µg）后 28 天，针对原始 SARS-CoV-2 和 Beta 变体的中和抗体反应高于第二次 mRNA-1273 剂量后 28 天（NCT04470427）初级系列。接种 50-µg mRNA-1273.211 加强针后 28 天和 180 天的抗体反应也高于接种 50-µg mRNA-1273 加强针后的抗体反应（NCT04405076），针对原始 SARS-CoV-2 和 Beta、Omicron BA.1 和 Delta 变体，所有预先指定的免疫原性目标均已达到。二价 mRNA-1273.211 加强针（50-µg）的安全性和反应原性与 mRNA-1273（50-µg）的加强针相似。初级系列免疫不会设定中和抗体反应的上限，并且二价疫苗的加强针会引发强大的反应，其滴度可能对 COVID-19 具有保护作用。这些结果表明，二价加强疫苗可以针对多种变体诱导强大、持久和广泛的抗体反应，为应对新出现的变体提供了一种新工具。
