研究性季节性流感疫苗mRNA-1010在健康成年人中的安全性和免疫原性：1/2期随机试验的最终结果

Safety and Immunogenicity of mRNA-1010, an Investigational Seasonal Influenza Vaccine, in Healthy Adults: Final Results From a Phase 1/2 Randomized Trial.

作者信息

Ananworanich Jintanat, Lee Ivan T, Ensz David, Carmona Lizbeth, Schaefers Kristi, Avanesov Andrei, Stadlbauer Daniel, Choi Angela, Pucci Alicia, McGrath Shannon, Kuo Hsiao-Hsuan, Henry Carole, Chen Ren, Huang Wenmei, Nachbagauer Raffael, Paris Robert

机构信息

Moderna, Inc, Cambridge, Massachusetts.

Meridian Clinical Research, Sioux City, Iowa.

出版信息

J Infect Dis. 2025 Feb 4;231(1):e113-e122. doi: 10.1093/infdis/jiae329.

BACKGROUND

Seasonal influenza remains a global public health concern. A messenger RNA (mRNA)-based quadrivalent seasonal influenza vaccine, mRNA-1010, was investigated in a first-in-human, phase 1/2 clinical trial conducted in 3 parts.

METHODS

In parts 1 to 3 of this stratified observer-blind study, adults aged ≥18 years were randomly assigned to receive a single dose (6.25-200 µg) of mRNA-1010 or placebo (part 1) or an active comparator (Afluria; parts 2 and 3). Primary study objectives were assessment of safety, reactogenicity, and humoral immunogenicity of mRNA-1010, placebo (part 1), or active comparator (parts 2 and 3). Exploratory end points included assessment of cellular immunogenicity (part 1) and antigenic breadth against vaccine heterologous strains (A/H3N2; parts 1 and 2).

RESULTS

In all study parts, solicited adverse reactions were reported more frequently for mRNA-1010 than placebo or Afluria, and most were grade 1 or 2 in severity. No vaccine-related serious adverse events or deaths were reported. In parts 1 and 2, a single dose of mRNA-1010 (25-200 µg) elicited robust day 29 hemagglutination inhibition titers that persisted through 6 months. In part 3, lower doses of mRNA-1010 (6.25-25 µg) elicited day 29 hemagglutination inhibition titers that were higher or comparable to those of Afluria for influenza A strains. When compared with Afluria, mRNA-1010 (50 µg) elicited broader A/H3N2 antibody responses (part 2). mRNA-1010 induced greater T-cell responses than placebo at day 8 that were sustained or stronger at day 29 (part 1).

CONCLUSIONS

Data support the continued development of mRNA-1010 as a seasonal influenza vaccine.

CLINICAL TRIALS REGISTRATION

NCT04956575 (https://clinicaltrials.gov/study/NCT04956575).

背景

季节性流感仍然是全球公共卫生关注的问题。一种基于信使核糖核酸（mRNA）的四价季节性流感疫苗mRNA-1010，在一项分3部分进行的首次人体1/2期临床试验中进行了研究。

方法

在这项分层观察者盲法研究的第1至3部分中，年龄≥18岁的成年人被随机分配接受单剂量（6.25 - 200μg）的mRNA-1010或安慰剂（第1部分）或活性对照品（Afluria；第2和3部分）。主要研究目标是评估mRNA-1010、安慰剂（第1部分）或活性对照品（第2和3部分）的安全性、反应原性和体液免疫原性。探索性终点包括评估细胞免疫原性（第1部分）和针对疫苗异源毒株（A/H3N2；第1和2部分）的抗原广度。

结果

在所有研究部分中，mRNA-1010组报告的主动不良反应比安慰剂组或Afluria组更频繁，且大多数严重程度为1级或2级。未报告与疫苗相关的严重不良事件或死亡。在第1和第2部分中，单剂量的mRNA-1010（25 - 200μg）在第29天引发了强劲的血凝抑制滴度，且持续了6个月。在第3部分中，较低剂量的mRNA-1010（6.25 - 25μg）引发的第29天血凝抑制滴度，对于甲型流感毒株而言，高于或与Afluria相当。与Afluria相比，mRNA-1010（50μg）引发了更广泛的A/H3N2抗体反应（第2部分）。mRNA-1010在第8天诱导的T细胞反应比安慰剂更大，且在第29天持续或更强（第1部分）。