近日，美国辉瑞公司Kelly Lindert团队研究了改良mRNA流感疫苗的有效性、免疫原性和安全性。2025年11月20日出版的《新英格兰医学杂志》发表了这项成果。

尽管使用了获得许可的疫苗，流感仍然是一个主要的健康负担。核苷修饰信使RNA（modRNA）流感疫苗在1-2期试验中显示出有前景的流感免疫原性和可接受的安全性。

在这项3期试验中，研究组在美国、南非和菲律宾的2022-2023年流感季节，随机分配年龄在18岁至64岁之间的健康成年人接种四价modRNA流感疫苗（modRNA组）或许可的灭活四价流感疫苗（对照组）。主要终点是相对疗效，定义为接种modRNA疫苗后与对照疫苗相比，至少14天内实验室确诊流感相关流感样疾病的参与者百分比降低，并对非效性和优越性进行分析。免疫原性通过血凝抑制（HAI）试验评估。研究组评估了接种后7天内的反应原性、1个月内的不良事件和6个月内的严重不良事件。研究组评估了modRNA组疫苗的有效性、免疫原性和安全性。

共有18476名参与者接受了随机分组：9225人被分配接受modRNA疫苗，9251人接受对照疫苗。在modRNA组57例和对照组87例的基础上，与流感样疾病的对照疫苗相比，modRNA疫苗的相对疗效为34.5%(95%可信区间为7.4至53.9)，这一发现符合非劣效性和优越性的标准。流感样疾病病例主要由A/H3N2和A/H1N1毒株引起，但几乎没有B毒株引起。抗体反应的非劣效性表明在流感病毒的A株，而不是B株。在两种疫苗组中均观察到主要的轻度或中度反应性，但在modRNA组中报告的反应性更频繁（总体局部反应，70.1%对43.1%；总体全身反应，65.8%对48.7%）。modRNA组中有5.6%的参与者发烧，对照组中有1.7%。两组的不良事件概况相似。

研究结果表明，modRNA疫苗在统计学上优于对照疫苗，对A/H3N2和A/H1N1株具有更强的免疫应答，但与更多的反应性事件相关。

附：英文原文

Title: Efficacy, Immunogenicity, and Safety of Modified mRNA Influenza Vaccine

Author: David Fitz-Patrick, Donald S. McVinnie, Lisa A. Jackson, Graham Crowther, Anita Geevarughese, Kevin D. Cannon, Lazaro M. Garcia, Yanely Pineiro Puebla, Zhuobiao Yi, Luke Cunliffe, Alok Maniar, Agnieszka M. Zareba, Claudia Ana Ianos, Emily Gomme, Kenneth Koury, Pirada Suphaphiphat Allen, Annaliesa S. Anderson, Alejandra Gurtman, Kelly Lindert

Issue&Volume: 2025-11-20

Abstract:

BACKGROUND

Influenza remains a major health burden despite the use of licensed vaccines. Nucleoside-modified messenger RNA (modRNA) influenza vaccines have shown promising immunogenicity against influenza and an acceptable safety profile in a phase 1–2 trial.

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. 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. Immunogenicity was evaluated by means of a hemagglutination inhibition (HAI) assay. We assessed reactogenicity within 7 days after vaccination, adverse events through 1 month, and serious adverse events through 6 months. We assessed vaccine efficacy, immunogenicity, and safety in the modRNA group.

RESULTS

A total of 18,476 participants underwent randomization: 9225 were assigned to receive the modRNA vaccine and 9251 to receive the control vaccine. 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. Cases of influenza-like illness were caused by A/H3N2 and A/H1N1 strains but almost no B strains. The noninferiority of the antibody response on HAI assay was shown for influenza A strains but not for B strains. 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%). Fever occurred in 5.6% of the participants in the modRNA group and in 1.7% of those in the control group. Adverse event profiles were similar in the two groups.

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.

DOI: NJ202511203932008

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2416779