Efficacy and Safety of an mRNA Seasonal Influenza Vaccine in Adults.

An investigational messenger RNA (mRNA)-based vaccine called mRNA-1010 encodes hemagglutinin glycoproteins from World Health Organization-recommended influenza strains.

一种名为mRNA-1010的实验性信使RNA（mRNA）疫苗编码了世界卫生组织推荐的流感病毒株的血凝素糖蛋白。

Methods

In this phase 3, double-blind, active-controlled trial, we randomly assigned adults 50 years of age or older to receive trivalent mRNA-1010 (37.5 μg, which includes 12.5 μg of each strain) or a licensed standard-dose comparator.

在这项III期、双盲、活性对照试验中，我们随机分配了50岁及以上的成人接受三价mRNA-1010（37.5微克，包括每株12.5微克）或已批准的标准剂量对照剂。

The primary efficacy end point was relative vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction (RT-PCR)-confirmed, protocol-defined influenza-like illness caused by influenza A or B, from at least 14 days after vaccination through the end of the influenza season.

主要疗效终点是针对通过逆转录聚合酶链反应（RT-PCR）确认的、由流感A或B引起的、符合方案定义的流感样疾病（ILI）的相对疫苗效力，从接种疫苗后至少14天起至流感季节结束。

Hypothesis testing was conducted hierarchically to assess noninferiority (lower boundary of the 95% confidence interval[CI], >-10%), superiority (lower boundary of the 95% CI, >0%), and a higher level of superiority (lower boundary of the 95% CI, >9.1%).

假设检验是分层进行的，以评估非劣效性（95%置信区间下限，>-10%）、优越性（95%置信区间下限，>0%）和更高水平的优越性（95%置信区间下限，>9.1%）。

Results

A total of 40,703 participants received mRNA-1010 (20,350 participants) or the standard-dose comparator (20,353 participants); the median follow-up was 181 days (range, 1 to 227).

共有40,703名参与者接受了mRNA-1010（20,350名参与者）或标准剂量对照（20,353名参与者）；中位随访时间为181天（范围，1至227天）。

RT-PCR-confirmed, protocol-defined influenza-like illness was observed in 411 of 20,179 recipients of mRNA-1010 (2.0%) and 557 of 20,124 recipients of the standard-dose comparator (2.8%), which corresponds to a relative vaccine efficacy of 26.6% (95% CI, 16.7 to 35.4), thereby meeting the criteria for noninferiority, superiority, and higher-level superiority.

经RT-PCR确认的、符合方案定义的流感样疾病在mRNA-1010的20,179名接种者中观察到411例（2.0%），而在标准剂量对照组的20,124名接种者中观察到557例（2.8%），这对应于相对疫苗效力为26.6%（95%置信区间，16.7至35.4），从而满足了非劣效性、优越性和更高级优越性的标准。

Solicited adverse reactions were more frequent with mRNA-1010 than with the standard-dose comparator (injection-site pain in 65.8% vs. 29.8%, fatigue in 45.1% vs. 20.3%, headache in 37.8% vs. 18.0%, and myalgia in 35.4% vs. 11.6%); most reactions were mild to moderate and transient.

mRNA-1010的接种者中，与标准剂量对照组相比，所诱导的不良反应更为频繁（接种部位疼痛为65.8%对比29.8%，疲劳为45.1%对比20.3%，头痛为37.8%对比18.0%，肌肉痛为35.4%对比11.6%）；大多数反应为轻度至中度且短暂。

Serious adverse events were reported in 2.2% of the recipients of mRNA-1010 (with three events considered by the investigator to be vaccine-related) and in 1.9% of the recipients of the standard-dose comparator (with two events considered by the investigator to be vaccine-related).

在 mRNA-1010 接种者中报告了 2.2% 的严重不良事件（调查员认为其中三起与疫苗相关），而在标准剂量对照组接种者中报告了 1.9% 的严重不良事件（调查员认为其中两起与疫苗相关）。

Conclusions

In this trial, mRNA-1010 was superior to standard-dose licensed vaccines for prevention of RT-PCR-confirmed, protocol-defined influenza-like illness in adults 50 years of age or older.

在这项试验中，mRNA-1010 在预防 50 岁及以上成人经 RT-PCR 确认的、符合方案定义的流感样疾病方面，优于标准剂量的已授权疫苗。

Solicited adverse reactions were more frequent with mRNA-1010.

与mRNA-1010相关的不良反应发生频率更高。

(Funded by Blackstone Life Sciences and Moderna; Fluent ClinicalTrials.gov number, NCT06602024.).

该研究由Blackstone Life Sciences和Moderna资助；Fluent ClinicalTrials.gov编号为NCT06602024。