新型冠状病毒刺突受体结合域和N端结构域mRNA疫苗的安全性和免疫原性
Safety and Immunogenicity of SARS-CoV-2 Spike Receptor-Binding Domain and N-Terminal Domain mRNA Vaccine.
作者信息
Chalkias Spyros, Pragalos Antionette, Akinsola Adebayo, Berman Gary, Ampajwala Madhavi, Meyer Jay, Schoch Lorraine, Zhou Wen, Paila Yamuna D, Deng Weiping, Feng Jing, de Windt Elizabeth, Edwards Darin, Miller Jacqueline, Das Rituparna
机构信息
Clinical Development, Infectious Diseases, Moderna, Inc, Cambridge, Massachusetts, USA.
CTI Clinical Trial and Consulting Services, Covington, Kentucky, USA.
出版信息
J Infect Dis. 2025 Apr 15;231(4):e754-e763. doi: 10.1093/infdis/jiaf022.
BACKGROUND
mRNA-1283 is an investigational coronavirus disease 2019 (COVID-19) mRNA vaccine encoding the receptor-binding and N-terminal domains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in contrast to the original mRNA-1273 vaccine, which encodes the full-length spike protein.
METHODS
A phase 2a, dose-ranging, observer-blind, randomized study conducted in adults (aged ≥18 years) previously vaccinated with mRNA-1273 evaluated the safety and immunogenicity of a single dose of mRNA-1283 (2.5, 5, and 10 µg) and its bivalent formulation, mRNA-1283.211 (5 and 10 µg; encoding original SARS-CoV-2 and Beta) against the comparator mRNA-1273 vaccine, 50 µg (part A). A subsequent, open-label study (part B) evaluated the safety and immunogenicity of a monovalent Omicron BA.1 vaccine, mRNA-1283.529 (5 and 10 µg).
RESULTS
A total of 340 participants were randomized in part A, and 200 participants were enrolled in part B. All dose levels of mRNA-1283 vaccines were well tolerated and increased the neutralizing antibody (nAb) responses at day 29 compared to baseline against SARS-CoV-2 D614G and Beta. The nAb responses elicited by mRNA-1283 were higher than those elicited by mRNA-1273. mRNA-1283.529 (part B) increased nAb at day 29 against Omicron BA.1. Antibody responses remained detectable for a year postvaccination.
CONCLUSIONS
mRNA-1283 was well tolerated and exhibited improved immunogenicity compared to mRNA-1273.
CLINICAL TRIALS REGISTRATION
NCT05137236.
背景
与编码全长刺突蛋白的原始mRNA-1273疫苗相比，mRNA-1283是一种正在研究的2019冠状病毒病（COVID-19）mRNA疫苗，其编码严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白的受体结合域和N端结构域。
方法
一项2a期、剂量范围、观察者盲法、随机研究在先前接种过mRNA-1273的成年人（年龄≥18岁）中进行，评估单剂量mRNA-1283（2.5、5和10μg）及其二价制剂mRNA-1283.211（5和10μg；编码原始SARS-CoV-2和贝塔毒株）相对于对照mRNA-1273疫苗50μg的安全性和免疫原性（A部分）。随后的一项开放标签研究（B部分）评估了单价奥密克戎BA.1疫苗mRNA-1283.529（5和10μg）的安全性和免疫原性。
结果
A部分共有340名参与者被随机分组，B部分招募了200名参与者。与基线相比，所有剂量水平的mRNA-1283疫苗耐受性良好，并在第29天增加了针对SARS-CoV-2 D614G和贝塔毒株的中和抗体（nAb）反应。mRNA-1283引发的nAb反应高于mRNA-1273引发的反应。mRNA-1283.529（B部分）在第29天增加了针对奥密克戎BA.1的nAb。接种疫苗后一年仍可检测到抗体反应。
结论
与mRNA-1273相比，mRNA-1283耐受性良好，免疫原性有所改善。
临床试验注册
NCT05137236。
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