Influenza and COVID-19 mRNA Vaccine (Moderna)

前言 当地时间8月5日，Moderna宣布FDA批准其mRNA流感疫苗mFLUSIVA（mRNA-1010）上市，用于50岁及以上人群。 这是全球首款获批的mRNA流感疫苗，预计未来数周将在美国零售药房供货，赶在2026—2027流感季前铺开。 但仔细拆解FDA的批文，会发现一个耐人寻味的细节：50至64岁拿到的是传统批准，65岁及以上拿到的却是加速批准。 同一款产品，同一份数据，FDA给出了两种不同的审评结论。 这不是监管的双标，而是对证据边界的精准划线。 一 为什么65岁以上 只给“有条件放行” 答案不在数据，而在对照疫苗的选择。 美国CDC多年来对65岁以上人群优先推荐高剂量、佐剂型或重组流感疫苗，而不是标准剂量。 但Moderna的4万人试验采用的是标准剂量对照。 一个击败了标准剂量的产品，并不等于能在老年人群中战胜强化版疫苗。 Moderna随后补做了一项2,992人的III期研究，头对头对阵赛诺菲高剂量流感疫苗Fluzone High-Dose。 这次比的是免疫原性。结果显示mRNA-1010的抗体应答达到非劣效和优效标准。 FDA据此同意用免疫原性作为替代终点，给65岁以上人群开了加速批准通道。 代价是Moderna必须补课。 公司计划开展一项约80万人的上市后研究，在2027—2029两个流感季中直接比较mFLUSIVA与CDC优先推荐的老年疫苗。 这次的批准只确认了mFLUSIVA有资格站上擂台，并没有宣布它彻底赢了比赛。 二 4万人的答卷 26.6%的效力意味着什么？ mFLUSIVA的III期试验规模不小。 11个国家、40,805名50岁以上受试者，头对头对比标准剂量灭活流感疫苗。 mFLUSIVA组流感确诊率为2.0%，对照组为2.8%，相对疫苗效力26.6%。 在50至64岁亚组中，这一数字是26.1%。 更值得关注的一个探索性终点：在需要住院、急诊或紧急医疗处理的重症病例中，rVE升至47.9%。 由于事件数较少，这个数字目前还只能看作一个积极的信号，而非定论。 但如果后续数据能持续验证，那将是mRNA疫苗在流感领域最有说服力的价值锚点。 按毒株拆分，由于试验期间甲型流感占了94%的病例，总体结果基本由A型驱动，针对H1N1和H3N2的rVE分别为29.6%和22.2%。 B/Victoria的病例太少，置信区间跨过零，尚无法得出可靠结论。 三 更高保护，伴随更高反应 安全方面，FDA整合分析了71,916名受试者数据，严重不良事件和特别关注不良事件在疫苗组和对照组之间基本平衡，未发现新的安全信号。 但反应原性的差异难以忽略。 mFLUSIVA组局部和全身不良反应发生率分别为67.5%和58.0%，对照组仅为32.1%和32.4%。 3级全身反应发生率5.5%，对照组仅0.9%。 注射部位疼痛、疲劳、头痛、肌痛、寒战等这些熟悉的mRNA副作用清单依然存在，大多轻至中度，中位持续约两天。 这是mRNA疫苗始终要面对的价值交换：更高的效力承诺，以更高的短期反应为代价。 四 赛道已变 从“能不能做”到“能不能赢” 新冠疫苗证明了mRNA能跑多快，但流感是另一种游戏。 这个市场已有鸡胚、细胞培养、重组蛋白、高剂量、佐剂型等多条成熟路线，mRNA不能只靠“平台叙事”占位，必须在头对头试验中证明真实增益。 mFLUSIVA首次给出了这样的证据。 传统流感疫苗从毒株选择到供应通常需要6—8个月，鸡胚培养还可能引入适应性突变。 mRNA路线理论上可以缩短周期、减少抗原漂移。 但这些优势能否在现实中兑现，取决于监管、生产和采购体系能否同步提速。 平台速度不会自动转化为公共卫生效力，mFLUSIVA上市后的真实世界表现才是答案。 对Moderna自身而言，这张批文还补上了另一块关键拼图。 其新冠—流感联合疫苗mRNA-1083此前因FDA要求补充流感组分效力证据而撤回美国上市申请。如今mFLUSIVA获批，为联合疫苗的重新推进扫除了核心障碍。 五 中国药企的“流感时刻” 还有多远？ Moderna落子之后，全球视线开始转向太平洋此岸。 国内mRNA企业已形成清晰的临床梯队。 艾博生物的冻干带状疱疹疫苗ABO1108于2026年6月启动III期，入组18,000例，是全球首个进入III期的带状疱疹mRNA疫苗，进度领先。 深信生物的带状疱疹疫苗IN001处于II期，瑞吉生物的RH110同样在II期阶段，嘉晨西海主攻自复制mRNA路线。 上市公司中，沃森生物联合蓝鹊推进RSV和带状疱疹管线，石药集团HPV治疗性疫苗SYS6026已启动II期。 2026年6月，CDE发布《预防用mRNA疫苗临床试验技术指导原则（试行）》，监管框架从模糊走向清晰。 当赛道从应急切换为常规，竞争规则也在悄然改变：谁能用差异化技术解决真实临床痛点，谁就能拿到下一轮入场券。 结语 mFLUSIVA的获批，把行业追问从“mRNA能不能做流感疫苗”推向了三个更现实的问题： 它能否在不同流感季持续维持相对优势？ 能否真正战胜老年人现有的强化型疫苗？ 更快的生产方式能否改变全球流感疫苗运转了数十年的供应节奏？ mRNA技术拿到了流感赛道的入场券。 但平台潜力不等于临床价值，真正的比赛才刚刚开始。 全文可扫码下方图片二维码获取

Despite a major curveball thrown by the FDA earlier this year, Moderna has managed to strike true with a U.S. approval for its mRNA-based influenza vaccine. The FDA on late Wednesday signed off on Moderna’s vaccine, christened mFlusiva, to prevent seasonal influenza in all adults ages 50 years and older. With the green light, Moderna has scooped up its fourth FDA nod and cleared the way for the first-ever flu shot leveraging mRNA technology in the United States. The vaccine’s odds of approval stateside were thrown into flux in February when the FDA issued Moderna a rare refusal to file (RTF) letter, citing concerns with the design of the phase 3 trial for the shot, at the time known as mRNA-1010. Moderna publicly pushed back against the FDA’s decision not to take up its application, and the agency—whose Center for Biologics Evaluation and Research (CBER) responsible for vaccines was at the time headed up by controversial director Vinay Prasad, M.D.—reversed course a little over a week later. The FDA’s concerns specifically came down to the use of a standard-dose flu vaccine as the comparator arm in one of the trial’s supporting mFlusiva’s approval. The FDA at the time suggested that it had issues because Moderna had not used “the best-available standard of care” in its study—a position the company disagreed with and noted that the FDA had not flagged as a problem when previously discussing trial protocols. At one additional checkpoint on the way to approval, the FDA’s Vaccines and Related Biological Products Advisory Committee voted unanimously that mFlusiva’s benefits outweighed its risks across both the 50-to-64-year age group and in patients ages 65 years and older. With regards to those age groups, mFlusiva has secured a traditional FDA approval in the 50-to-64-year bracket and an accelerated nod in the older group. The decision was backed up by data from a pair of phase 3 trials, with the study in the younger patient group comparing mFlusiva’s relative vaccine efficacy, among other measures, against a standard-dose comparator shot. The study in adults ages 65 and up pitted mFlusiva against a high-dose inactivated flu shot but with immunogenicity as the primary objective. As required by an accelerated approval, Moderna noted that it will run a postmarketing trial to confirm its vaccine’s benefit in the older patient population. With the colder months drawing nearer, Moderna says it expects to make mFlusiva available in the U.S. for the 2026-2027 respiratory virus season. The new vaccine will join the stable of Moderna’s other mRNA vaccines Spikevax and mNexspike for COVID-19, and mResvia in respiratory syncytial virus. "The FDA approval of mFlusiva, our fourth approved product in the United States and the first mRNA-based flu vaccine, demonstrates the continued strength and versatility of our mRNA platform," Moderna helmsman Stéphane Bancel said in a Wednesday statement. "Flu remains a significant public health challenge, and mFlusiva provides an important new option for America's seniors,” he continued. “This approval also reflects the ongoing potential of our mRNA platform to help address important public health challenges through continued scientific innovation.” Outside the U.S., Moderna’s mFlusiva application has been taken under review in the European Union, Canada and Australia. While the solo flu shot is awaiting a verdict in Europe, the EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended approval for Moderna’s mCombriax in patients ages 50 and up. That mRNA vaccine is designed to confer protection against COVID and flu in a single combo shot.