Tetravalent influenza vaccine(Split, inactivated)(Sanofi)

Total revenue of $239 million in the second quarter of 2025 Received FDA BLA approval for Nuvaxovid™, the only recombinant protein-based, non-mRNA COVID-19 vaccine available in the U.S.; approval triggered $175 million milestone payment from Sanofi Completed transition of Nuvaxovid™ commercial leadership in the U.S. to Sanofi for the 2025-2026 COVID-19 vaccination season COVID-19-Influenza-Combination and stand-alone influenza vaccine candidates showed robust immune responses in initial cohort of a Phase 3 trial with new T-cell response data in both Novavax vaccine candidates numerically higher than in the comparator Fluzone HD arm Updated Full Year 2025 Revenue Framework and Financial Guidance Company to host conference call today at 8:30 a.m. ET GAITHERSBURG, Md., Aug. 6, 2025 /PRNewswire/ -- Novavax, Inc. (Nasdaq: NVAX) today announced its financial results and operational highlights for the second quarter ended June 30, 2025. "This quarter we continued to progress our growth strategy with key achievements including BLA approval for our COVID-19 vaccine, positive data from our COVID-19-Influenza-Combination and stand-alone influenza programs, advancement of our early-stage pipeline, and progression of our partnership strategy," said John C. Jacobs, President and Chief Executive Officer, Novavax. "We look forward to continuing to build on this foundation into the second half of the year." Second Quarter 2025 and Recent Highlights Strategic Priority #1: Sanofi Partnership In May 2025, the U.S. Food and Drug Administration (FDA) approved the Nuvaxovid™ Biologics License Application (BLA) for prevention of COVID-19 in adults 65 years and older and individuals aged 12 through 64 years who have at least one underlying condition that puts them at high risk for severe outcomes from COVID-19. BLA approval triggered a $175 million milestone payment from Sanofi. Completed transition of Nuvaxovid commercial leadership in the U.S. to Sanofi for the 2025-2026 COVID-19 vaccination season. Transfers of marketing authorization to Sanofi for U.S. and European Union (EU) markets are expected in the fourth quarter of 2025 which will trigger an additional $50 million in combined milestones from Sanofi. Strategic Priority #2: Enhance Existing Partnerships and Leverage our Technology Platform and Pipeline to Forge Additional Partnerships In June 2025, the company reported initial cohort data for the Phase 3 trial for its COVID-19-Influenza-Combination (CIC) and stand-alone seasonal influenza vaccine candidates, showing robust immune responses for both candidates. This descriptive data set will help inform a potential future registrational Phase 3 program. Novavax intends to partner these programs and this trial reflects the completion of material investment by Novavax. Discussions are ongoing with potential partners for these late-stage assets. New T-cell response data in both CIC and stand-alone influenza vaccine candidates were numerically higher than the Fluzone HD comparator arm indicating the potential for an increased duration of protection. In May 2025, Novavax and Takeda Pharmaceuticals announced significantly improved terms for their partnership to support ongoing commercialization of Nuvaxovid in Japan. Takeda filed for approval of the updated Nuvaxovid vaccine in June and is on track to be on the market for the fall respiratory season in Japan. R21/Matrix-M®, a malaria vaccine developed in partnership with Serum Institute of India and Oxford University, continued to make meaningful progress in addressing the urgent and unmet needs of malaria-endemic regions with 20 million doses sold since launch in mid-2024. In the first quarter of 2025, Novavax announced material transfer agreements with three pharmaceutical companies to explore the utility of Matrix-M in their portfolios. These arrangements have led to discussions with potential business partners to develop new vaccines and improve existing vaccines. Strategic Priority #3: Advance our Technology Platform and Early-stage Pipeline In July 2025, the Company announced preclinical data demonstrating that Novavax's H5N1 avian pandemic influenza vaccine candidate induced robust immune responses by either single or two-dose intranasal or intramuscular administration in primed non-human primates. The results were published in Nature Communications. Continued advancement of early-stage preclinical research for H5N1 avian pandemic influenza, respiratory syncytial virus combinations, varicella-zoster virus (shingles) and Clostridioides difficile colitis vaccine candidates. Generated preliminary positive data using Matrix-M with an oncology vaccine candidate with potential future application across several tumor types. Continued work on new potential Matrix formulations intended to improve upon and expand the utility of Matrix-M. Notes Nuvaxovid Sales reflects product sales where Novavax is the commercial market lead and records revenue related to the sales and distribution of our COVID-19 vaccine. Supply Sales includes sales of finished product, adjuvant and other supplies from Novavax to our license partners. Sanofi includes revenue recognized under our license agreement including upfront payments, milestones, royalties and transition services reimbursement. Other Partners include upfronts, royalties and milestone revenue under our licensing agreements including Serum Institute and SK bioscience. Second Quarter 2025 Financial Results Total revenue for the second quarter of 2025 was $239 million, compared to $415 million in the same period in 2024. Licensing, Royalties and Other Revenue of $229 million in the second quarter of 2025 includes a $175 million milestone earned related to the Nuvaxovid BLA approval. Cost of sales for the second quarter of 2025 was $15 million, compared to $46 million in the same period in 2024. Research and development (R&D) expenses for the second quarter of 2025 were $79 million, compared to $107 million in the same period in 2024. The decrease was primarily due to reductions in overall expenditures related to COVID-19 vaccine development and the elimination of the related commercial manufacturing network infrastructure. Selling, general and administrative (SG &A) expenses for the second quarter of 2025 were $44 million, compared to $101 million for the same period in 2024. The 57% decrease was primarily due to the transition of lead commercial activities to Sanofi and the elimination of commercial infrastructure plus ongoing general administrative cost reduction efforts. Net income for the second quarter of 2025 was $107 million, compared to net income of $162 million in the same period in 2024. Cash, cash equivalents, marketable securities and restricted cash (Cash) were $628 million as of June 30, 2025, compared to $938 million as of December 31, 2024. Receipt of the $175 million milestone earned in the second quarter of 2025 related to the Nuvaxovid BLA approval is expected in the third quarter of 2025. Financial Framework Nuvaxovid Postmarketing Commitment Study As previously announced, in May 2025, our BLA for Nuvaxovid received U.S. FDA approval and with that approval came an FDA request to complete a postmarketing commitment (PMC) study. The PMC is anticipated to occur during 2025 and 2026 and cost between $70 million to $90 million to complete. Novavax will conduct this study on behalf of Sanofi and Novavax will be reimbursed approximately $55 million (at midpoint) or 70% of total costs. The Novavax cost share of approximately $25 million (at midpoint) has been absorbed within the Company's existing combined R&D and SG&A expense targets and is capped under the agreement at the currently agreed upon costs estimates. For Full Year 2025, this is expected to result in a $20 million increase to Adjusted Licensing, Royalties and Other Revenue, where Novavax records partner cost reimbursement as revenue, and an equal $20 million increase to combined R&D and SG&A expenses. Full Year 2025 Financial Guidance Novavax provides updated Full Year 2025 Financial Guidance for combined R&D and SG&A expenses and currently expects to achieve the following results: Full Year 2025 Revenue Framework Novavax transitioned lead commercial responsibility of Nuvaxovid beginning with the 2025-2026 COVID-19 vaccination season to Sanofi for select markets. Since Novavax is reliant on Sanofi's sales forecasts for certain revenue components, these are not included in the Full Year 2025 Revenue Framework. For 2025, Novavax currently expects to achieve Adjusted Total Revenue1 of between $1,000 million and $1,050 million. Adjusted Total Revenue is a non-GAAP financial measure. Adjusted Total Revenue is total revenue excluding Sanofi Supply Sales, Sanofi Royalties and Sanofi Influenza-COVID-19 Combination and Matrix-M related Milestones. See "Non-GAAP Financial Measures" below. Nuvaxovid Product Sales of $610 million include $603 million in revenue recognized in the first quarter of 2025 from the termination of the Canada and New Zealand Advance Purchase Agreements, plus sales by Novavax in the U.S. and select markets outside the U.S. $25 million to $40 million in Adjusted Supply Sales associated with collaborations with the Serum Institute on R21/Matrix-M and collaboration partners for COVID-19 vaccine, including Serum, SK bioscience and Takeda. Beginning in 2025, Supply Sales are included in Product Sales. Adjusted Licensing, Royalties and Other Revenue is a non-GAAP financial measure, Adjusted Licensing, Royalties and Other Revenue is Licensing, Royalties and Other Revenue excluding Sanofi Royalties and Sanofi Influenza-COVID-19 Combination and Matrix-M related milestones. See "Non-GAAP Financial Measures" below. Adjusted Licensing, Royalties and Other Revenue includes $225 million in U.S. BLA & Marketing Authorizations Milestones. Novavax earned a $175 million milestone upon the approval of the COVID-19 U.S. BLA in May 2025 and is eligible to receive two separate $25 million milestone payments upon the transfer to Sanofi of the Marketing Authorizations for the U.S. and EU markets, respectively. $45 million to $70 million in R&D Reimbursement. Under the Sanofi co-exclusive licensing agreement (CLA), Novavax is eligible to receive reimbursement for costs incurred related to select R&D and technology transfer activities during the transition performance period that is expected to run through the end of 2026 and beginning in Q3 2025, the reimbursement of a share of costs associated with the Nuvaxovid PMC is expected in 2025 and 2026. $35 million to $45 million in Other Partner related revenue including royalties and milestones from the Serum Institute on R21/Matrix-M and collaboration partners for COVID-19 vaccine, including Serum, SK bioscience and Takeda. $60 million amortization related to the $500 million Upfront Payment and the $50 million Database Lock Milestone from Sanofi. Revenue recognition will occur over the performance period through 2026. During 2024, a combined amortization of $440 million was recorded, and $60 million and $50 million are expected for 2025 and 2026, respectively. All remaining milestone payments under the Sanofi CLA will be recorded to revenue in the periods when earned. Components of Revenue excluded from the Full Year 2025 Revenue Framework are described below. Sanofi Supply Sales Novavax will sell Nuvaxovid commercial supply to Sanofi for the 2025-2026 COVID-19 vaccination season and the reimbursement for this supply will be recorded as product sales. Sanofi Royalties Sanofi will initiate lead commercial responsibility for the 2025-2026 COVID-19 vaccination season in select markets, including the U.S. Novavax is eligible to receive royalties in the high teens to low twenties percent on Sanofi sales. Sanofi Influenza-COVID-19 Combination and Matrix-M Related Milestones Novavax is eligible to receive up to $350 million in Phase 3 development and commercial launch milestone payments associated with Sanofi Influenza-COVID-19 combination products. For each new vaccine using Matrix-M, Novavax is eligible to receive up to $200 million in launch and sales milestones and mid-single digit sales royalties for 20 years. Conference Call Novavax will host its quarterly conference call today at 8:30 a.m. ET. To join the call without operator assistance, you may register and enter your phone number at to receive an instant automated call back. You may also dial direct to be entered to the call by an operator. The dial-in numbers for the conference call are (888) 880-3330 (Domestic) or (+1) (646) 357-8766 (International). Participants will be prompted to request to join the Novavax, Inc. call. A replay of the conference call will be available starting at 11:30 a.m. ET on August 6, 2025, until 11:59 p.m. ET on August 13, 2025. To access the replay by telephone, dial (800) 770-2030 (Domestic) or (+1) (609) 800-9909 (International) and use passcode 3041984#. A webcast of the conference call can also be accessed on the Novavax website at ir.novavax.com/events. A replay of the webcast will be available on the Novavax website until September 5, 2025. About Novavax Novavax, Inc. (Nasdaq: NVAX) tackles some of the world's most pressing health challenges with its scientific expertise in vaccines and its proven technology platform, including protein-based nanoparticles and its Matrix-M adjuvant. The Company's growth strategy seeks to optimize its existing partnerships and expand access to its proven technology platform via R&D innovation, organic portfolio expansion in infectious disease and beyond, and forging new partnerships and collaborations with other companies. Please visit novavax.com and LinkedIn for more information. Non-GAAP Financial Measures The Company presents the following non-GAAP financial measures in this press release: Adjusted Total Revenue and Adjusted Licensing, Royalties and Other Revenue. Non-GAAP financial measures refer to financial information adjusted from financial measures prepared in accordance with accounting principles generally accepted in the United States (GAAP). The Company believes that the presentation of these adjusted financial measures is useful to investors as they provide additional information on comparisons between periods by including certain items that affect overall comparability. The Company uses these non-GAAP financial measures for business planning purposes and to consider underlying trends of its business. Non-GAAP financial measures should be considered in addition to, and not as an alternative for, the Company's reported results prepared in accordance with GAAP. Our use of non-GAAP financial measures may differ from similar measures reported by other companies and may not be comparable to other similarly titled measures. The Company is unable to reconcile these forward-looking non-GAAP financial measures to the most directly comparable GAAP measures without unreasonable effort because the Company is reliant on Sanofi sales forecasts for certain revenue categories, which are not available. Forward-Looking Statements This press release contains forward-looking statements relating to the future of Novavax, its mission; its corporate strategy and operating plans, objectives and prospects; its value drivers and strategic priorities, its partnerships, including expectations with respect to potential royalties, milestones, and cost reimbursement, and plans for additional potential partnering activities; its expectations regarding manufacturing capacity, timing, production and delivery for its COVID-19 vaccine; the transition of the lead responsibility for commercialization of Novavax's COVID-19 vaccine to Sanofi beginning with the 2025-2026 vaccination season; the development of Novavax's clinical and preclinical product candidates and pipeline advancement opportunities, including with respect to new Matrix formulations; the conduct, timing and potential results from clinical trials and other preclinical and postmarketing studies; scope, expectations as to the timing and outcome of future and pending regulatory filings and actions; the conduct of our postmarketing commitment ("PMC") study requested by the U.S. FDA following the U.S. FDA's approval of the BLA for our COVID-19 Vaccine and the expected costs and timing associated with the PMC study; full year 2025 financial guidance and revenue framework; negotiations regarding Novavax's existing advance purchase agreements; and Novavax's future financial or business performance. Novavax cautions that these forward-looking statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include, without limitation, challenges or delays in obtaining regulatory authorization or approval for its COVID-19 vaccine, including for future COVID-19 variant strain changes, its CIC vaccine candidate, its stand-alone influenza vaccine candidate or other product candidates; Novavax's ability to successfully and timely manufacture, market, distribute, or deliver its COVID-19 vaccine; challenges related to Novavax's partnership with Sanofi, including collaboration on the Nuvaxovid PMC, and in pursuing additional partnership opportunities; challenges satisfying, alone or together with partners, various safety, efficacy, and product characterization requirements, including those related to process qualification, assay validation and stability testing, necessary to satisfy applicable regulatory authorities; challenges or delays in conducting clinical trials or studies for its product candidates, including the Nuvaxovid PMC; manufacturing, distribution or export delays or challenges; Novavax's substantial dependence on SII and Serum Life Sciences Limited for co-formulation and filling Novavax's COVID-19 vaccine and the impact of any delays or disruptions in their operations; difficulty obtaining scarce raw materials and supplies including for its proprietary adjuvant; resource constraints, including human capital and manufacturing capacity; constraints on Novavax's ability to pursue planned regulatory pathways, alone or with partners; challenges in implementing its global restructuring and cost reduction plan; Novavax's ability to timely deliver doses; challenges in obtaining commercial adoption and market acceptance of its COVID-19 vaccine or any COVID-19 variant strain containing formulation, or for its CIC vaccine candidate and stand-alone influenza vaccine candidate or other product candidates; challenges meeting contractual requirements under agreements with multiple commercial, governmental, and other entities, including requirements to deliver doses that may require Novavax to refund portions of upfront and other payments previously received or result in reduced future payments pursuant to such agreements and challenges in negotiating, amending or terminating such agreements; challenges related to the seasonality of vaccinations against COVID-19 or influenza; challenges and uncertainty related to regulatory development; challenges related to the demand for vaccinations against COVID-19 or influenza; challenges in identifying and successfully pursuing innovation expansion opportunities, including with respect to Novavax's Matrix-M adjuvant; Novavax's expectations as to expenses and cash needs may prove not to be correct for reasons such as changes in plans or actual events being different than its assumptions; and those other risk factors identified in the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Novavax's Annual Report on Form 10-K for the year ended December 31, 2024, and subsequent Quarterly Reports on Form 10-Q, as filed with the Securities and Exchange Commission (SEC). We caution investors not to place considerable reliance on forward-looking statements contained in this press release. You are encouraged to read our filings with the SEC, available at and , for a discussion of these and other risks and uncertainties. The forward-looking statements in this press release speak only as of the date of this document, and we undertake no obligation to update or revise any of the statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties. Contacts: Investors Luis Sanay, CFA 240-268-2022 [email protected] Media Giovanna Chandler 844-264-8571 [email protected] SOURCE Novavax, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

摘要：流感疫苗是预防流感的重要手段，但不同生产工艺的疫苗效果可能存在差异。本文基于一项针对 50 岁及以上成年人的前瞻性研究，对比了裂解病毒疫苗（split-virion vaccine）和亚单位疫苗（subunit vaccine）的临床有效性。研究通过分析 2008-2009、2010-2011、2011-2012 三个流感季节的病例数据发现：裂解病毒疫苗的整体有效性为77.8%，显著高于亚单位疫苗的44.2%，两者差异达 33.5%。这一结果提示，疫苗生产工艺可能影响保护效果，尤其在依赖细胞免疫反应的老年人中更为明显。本文将详细解读研究背景、方法、结果及意义，为公众和医护人员选择流感疫苗提供参考。 一、研究背景：两种流感疫苗的 “同源异路” 流感是全球范围内危害公共健康的重要呼吸道传染病，尤其对老年人（≥65 岁）和有基础疾病人群威胁更大。目前，市场上的灭活流感疫苗主要通过两种工艺生产：分裂病毒体法和亚单位法，二者 “同源” 却 “异路”。1.1 疫苗生产工艺的核心差异 两种疫苗的生产起点相同：均从无病原体鸡蛋中培养流感病毒，再用表面活性剂破坏病毒囊膜。但后续步骤不同： 裂解病毒疫苗：不经过进一步纯化，因此保留了更多病毒内部蛋白（如核蛋白、聚合酶、基质蛋白等），蛋白质含量更高，通常反应原性（接种后局部或全身反应）略强。 亚单位疫苗：通过离心等方法进一步纯化，去除了病毒内部核心，仅保留血凝素（hemagglutinin，HA）等表面蛋白，反应原性较低，这也是其最初被研发的重要原因。 由于两种疫苗的血凝素含量相似，通过血凝抑制试验（疫苗获批的关键指标）检测时，抗体反应相近，因此长期被认为保护效果相当。但近年来研究发现，血凝素抗体并非完美的保护指标，而细胞免疫反应（尤其是针对病毒内部蛋白的 T 细胞反应）在流感防护中可能同样重要 —— 这正是两种疫苗可能产生差异的关键。1.2 老年人为何需要特别关注疫苗效果？ 老年人的免疫系统随年龄增长衰退，抗体反应减弱，但细胞免疫在清除病毒、减轻症状中作用更突出。研究发现，针对病毒内部蛋白的细胞免疫（如 CD8⁺ T 细胞）可降低病毒载量、减少发病严重性。由于裂解病毒疫苗保留更多内部蛋白，理论上可能刺激更强的细胞免疫，更适合老年人。但这一理论是否转化为实际临床效果，此前缺乏直接证据。二、研究方法：严谨设计下的 “头对头” 对比 为回答两种疫苗的临床有效性差异，研究团队采用病例阳性 - 对照测试阴性设计（目前评估疫苗效果的主流方法），对美国田纳西州纳什维尔地区的患者数据进行了分析。2.1 研究对象与时间 纳入人群：2008-2009、2010-2011、2011-2012 三个流感季节中，因急性呼吸道疾病或 “不明原因发热” 就诊的 50 岁及以上成年人。排除 2009-2010 季节（因甲型 H1N1 大流行疫苗推出较晚，数据不稳定）。 就诊地点：4 家监测医院、1 个急诊科、1 个急性护理门诊。2.2 数据收集与定义 基本信息：通过标准表格记录症状、吸烟史、疫苗接种史（包括接种时间、厂商、批号）、基础疾病（如糖尿病、心脏病、免疫抑制等）；通过病历提取人口学数据、实验室检测结果等。 疫苗接种验证：接种状态需满足 “症状发作前至少 2 周接种”，并通过医疗机构、零售药店、雇主等多方核实（避免自报偏差）。 病例与对照定义： 流感阳性病例：经逆转录聚合酶链反应（RT-PCR） 检测流感病毒阳性（重复检测确认）。 流感阴性对照：RT-PCR 检测阴性，但样本中存在 β- 肌动蛋白或 RNase P（确保样本合格）。 排除标准：检测结果不确定、疫苗状态不明或厂商信息缺失者。2.3 分析方法 统计工具：用 Pearson χ² 检验分析分类变量（如性别、种族），Wilcoxon 秩和检验分析连续变量（如年龄）；通过逻辑回归模型计算疫苗有效性（VE），公式为 “（1-调整后比值比）×100%”。 调整因素：年龄、性别、种族、吸烟状态、基础疾病、流感季节、就诊地点等潜在混杂因素。 敏感性分析：针对疫苗厂商信息缺失的 18 名参与者，通过多重插补法补充数据后重新分析，验证结果稳定性。三、研究结果：分裂病毒体疫苗效果显著更优 研究共纳入 840 名受试者，最终 539 人数据完整（471 人流感阴性，68 人流感阳性）。结果显示，两种疫苗的临床有效性存在明显差异。3.1 参与者基本特征 如表 1 所示，流感阳性者与阴性者、不同疫苗接种者的特征存在一定差异： 流感阳性者更年轻（中位年龄 61.3 岁 vs 65.9 岁，P<0.001），更可能未接种疫苗或接种亚单位疫苗（P<0.001），且更多在急诊科或门诊就诊（P=0.001）。 未接种疫苗者中，黑人比例更高（26%）、吸烟者更多（30%）、基础疾病更少（如心血管病 34% vs 接种者 45%-49%），提示疫苗接种行为可能与健康状态相关。 接种分裂病毒体疫苗者的流感发生率（5.4%）显著低于亚单位疫苗接种者（12%，P=0.025）。 表 1 研究参与者按流感和疫苗状态的人口统计学特征 3.2 疫苗有效性对比 整体来看，裂解病毒疫苗的保护效果显著优于亚单位疫苗： 裂解病毒疫苗：有效性 77.8%（95% 置信区间 58.5%-90.3%），意味着接种后可降低 77.8% 的流感相关就医风险。 亚单位疫苗：有效性 44.2%（95% 置信区间 - 11.8%-70.9%），置信区间包含 0，提示其效果可能不显著。 效果差异：两种疫苗有效性相差 33.5%（95% 置信区间 6.9%-86.7%），且差异具有统计学意义。3.3 不同细分群体的效果差异 如图 1 所示，按年龄、流感季节、病毒类型分析后，裂解病毒疫苗的优势依然明显： 年龄分组：50-64 岁人群中，裂解病毒疫苗有效性 78.7%，亚单位 43.0%；≥65 岁人群中，裂解病毒 74.0%，亚单位 32.1%（亚单位疫苗置信区间包含 0）。 流感季节：2008-2009 和 2010-2011 季节中，裂解病毒疫苗有效性分别为 97.5% 和 72.5%，亚单位为 87.1% 和 3.9%（2010-2011 季节亚单位效果接近无意义）。 病毒类型：对甲型 H1N1 和乙型流感，裂解病毒疫苗有效性分别为 78.4% 和 89.7%，亚单位为 56.1% 和 19.8%（乙型流感中亚单位效果无显著意义）。 图 1 亚单位疫苗和分裂病毒体疫苗的有效性（注：图中展示了整体及按年龄、季节、病毒类型划分的疫苗有效性，误差线为 95% 置信区间）3.4 敏感性分析结果 补充缺失数据后重新分析，结果与原分析一致：裂解病毒疫苗有效性 74.8%（53.3%-89.2%），亚单位46.3%（-4.4%-75.9%），差异 28.6%（0.85%-73.1%），进一步支持结论的可靠性。四、讨论：为何分裂病毒体疫苗更有效？ 研究结果表明，分裂病毒体疫苗在 50 岁及以上人群中预防流感相关就医的效果更优，这一发现背后可能有多重原因。4.1 细胞免疫反应的 “隐形贡献” 两种疫苗的血凝素抗体反应相似，但分裂病毒体疫苗因保留更多内部蛋白（如核蛋白、基质蛋白），可刺激更强的细胞免疫。研究证实，针对内部蛋白的 T 细胞反应（如 IFN-γ 分泌增加）与流感保护力直接相关 —— 在老年人中，这种细胞免疫可能比抗体反应更重要。例如，McElhaney 等发现，T 细胞分泌的 IFN-γ/IL-10 比值、颗粒酶 B 水平等细胞免疫指标，比抗体滴度更能预测流感防护效果。4.2 与其他研究的对比：为何结果有差异？ 此前欧洲一项研究（2012-2013 季节）未发现两种疫苗效果差异，可能原因包括： 研究人群不同：欧洲研究以门诊患者为主（轻症），而本研究 77% 为住院患者（重症），提示裂解病毒疫苗可能更擅长预防重症流感。 疫苗具体类型不同：本研究中 99% 的亚单位疫苗为 Fluvirin，38% 的分裂病毒体疫苗为 Fluzone，而欧洲研究未明确疫苗品牌，可能存在产品差异。 样本量与统计 power：两项研究的置信区间均较宽，可能受样本量限制。4.3 其他潜在影响因素 神经氨酸酶（NA）含量：NA 是病毒另一种关键蛋白，可减少病毒传播和症状严重程度，但疫苗中 NA 含量未标准化。分裂病毒体疫苗可能含更多 NA，从而增强保护。 疫苗株匹配度：2008-2009 和 2011-2012 季节，疫苗与乙型流感株匹配度低，但分裂病毒体疫苗对乙型流感的效果仍达 89.7%，提示其可能对株匹配不佳的流感也有一定保护力。五、研究局限与未来方向 尽管结果有说服力，本研究仍存在局限： 样本量与地区限制：仅 3 个流感季节、1 个地区的数据，样本量较小（尤其≥70 岁人群细分分析时），可能影响结果普适性。 亚单位疫苗单一：99% 的亚单位疫苗为同一品牌，可能无法代表所有亚单位疫苗的效果。 未评估长期效果：研究仅关注短期就医风险，未涉及长期保护（如 6 个月以上）或对死亡的影响。 未来研究需扩大样本量、纳入更多地区和季节，验证不同品牌疫苗的效果；同时深入探索内部蛋白和细胞免疫在防护中的作用，为疫苗研发提供靶点。六、对公众与临床的启示 对于 50 岁及以上人群，选择流感疫苗时可优先考虑裂解病毒疫苗（如 Fluzone 标准剂量），尤其有基础疾病或年龄较大者。但需注意： 疫苗效果受个体免疫状态、病毒株匹配度等影响，接种仍是最有效的预防手段，不可因 “效果差异” 放弃接种。 临床医生应结合患者情况推荐疫苗，并加强接种记录的完整性（如准确记录厂商和批号），为后续研究提供数据支持。 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。