Efficacy, Immunogenicity, and Safety of Modified mRNA Influenza Vaccine.

Nucleoside-modified messenger RNA (modRNA) influenza vaccines have shown promising immunogenicity against influenza and an acceptable safety profile in a phase 1-2 trial.

在1-2期试验中，核苷酸修饰的信使RNA（modRNA）流感疫苗对流感显示出有希望的免疫原性，并且具有可接受的安全性。

Methods

In this phase 3 trial, we randomly assigned healthy adults between the ages of 18 and 64 years to receive either a quadrivalent modRNA influenza vaccine (modRNA group) or a licensed inactivated quadrivalent influenza vaccine (control group) during the 2022-2023 influenza season in the United States, South Africa, and the Philippines.

在这项III期试验中，我们将18至64岁的健康成人随机分配，以接受四价modRNA流感疫苗（modRNA组）或已获批准的灭活四价流感疫苗（对照组），在美国、南非和菲律宾的2022-2023流感季节接种。

The primary end point was relative efficacy, defined by the reduction in the percentage of participants with laboratory-confirmed influenza associated with influenza-like illness at least 14 days after vaccination with the modRNA vaccine, as compared with the control vaccine, and analyzed for noninferiority and superiority.

主要终点是相对效力，通过modRNA疫苗接种后至少14天，与对照疫苗相比，实验室确诊的流感与流感样疾病相关的参与者的百分比减少来定义，并分析非劣效性和优越性。

Immunogenicity was evaluated by means of a hemagglutination inhibition (HAI) assay.

通过血凝抑制(HAI)试验评估了免疫原性。

We assessed reactogenicity within 7 days after vaccination, adverse events through 1 month, and serious adverse events through 6 months.

我们在接种疫苗后7天内评估了反应原性，1个月内评估了不良事件，以及6个月内评估了严重不良事件。

We assessed vaccine efficacy, immunogenicity, and safety in the modRNA group.

我们评估了mRNA修饰疫苗组的疫苗效力、免疫原性和安全性。

Results

A total of 18,476 participants underwent randomization: 9225 were assigned to receive the modRNA vaccine and 9251 to receive the control vaccine.

共有18,476名参与者进行了随机分组：9225人被分配接受mRNA修饰疫苗，9251人被分配接受对照疫苗。

The relative efficacy of the modRNA vaccine as compared with the control vaccine against influenza-like illness was 34.5% (95% confidence interval[CI], 7.4 to 53.9) on the basis of 57 cases in the modRNA group and 87 cases in the control group, a finding that met the criteria for both noninferiority and superiority.

与对照疫苗相比，modRNA疫苗对类流感疾病的相对有效性为34.5%（95%置信区间[CI]，7.4至53.9），基于modRNA组57例和对照组87例病例，这一发现满足了非劣效性和优越性的标准。

Cases of influenza-like illness were caused by A/H3N2 and A/H1N1 strains but almost no B strains.

类流感疾病病例由A/H3N2和A/H1N1株引起，但几乎不涉及B株。

The noninferiority of the antibody response on HAI assay was shown for influenza A strains but not for B strains.

抗体对流感A型病毒株的血凝素抑制(HAI)试验反应的非劣效性得到了证明，但对B型病毒株则没有。

Primarily mild or moderate reactogenicity was observed in both vaccine groups but was reported more frequently in the modRNA group (overall local reactions, 70.1% vs. 43.1%; overall systemic events, 65.8% vs. 48.7%).

在两个疫苗组中主要观察到轻度或中度的反应原性，但modRNA组报告更为频繁（总体局部反应，70.1%对比43.1%；总体全身事件，65.8%对比48.7%）。

Fever occurred in 5.6% of the participants in the modRNA group and in 1.7% of those in the control group.

modRNA组中有5.6%的参与者出现发热，对照组中则为1.7%。

Adverse eventprofiles were similar in the two groups.

两组的不良事件特征相似。

Conclusions

The modRNA vaccine had statistically superior efficacy over the control vaccine, with greater immune responses to A/H3N2 and A/H1N1 strains, but was associated with more reactogenicity events.

与对照疫苗相比，modRNA疫苗在A/H3N2和A/H1N1株的免疫反应方面具有统计学上显著的优越性，但与更多的反应原性事件相关。

(Funded by Pfizer; C4781004 ClinicalTrials.gov number, NCT05540522.)See also in NEJM Evidence: Human clinical trial of a nucleoside-modified mRNA influenza vaccine.

(由辉瑞资助; ClinicalTrials.gov编号C4781004，NCT05540522。)也在NEJM Evidence中看到：一种核苷酸修饰的mRNA流感疫苗的人体临床试验。