SARS-CoV-2 Spike Protein Vaccine (Recombinant) (Novavax)

摘要：你可能想不到，我们接种的新冠疫苗、对抗癌症的免疫疗法，背后可能藏着 “昆虫的功劳”。昆虫细胞系作为一种神奇的 “生物工厂”，既能高效生产重组蛋白，又能完成复杂的蛋白修饰，还能大幅降低制药成本。本文从昆虫细胞培养的百年发展史说起，拆解它的制药原理、技术突破和实际应用，带大家认识这个生物制药界的 “低调王者”，看看小小的昆虫细胞如何撑起疫苗、抗癌药等多种生物制品的生产重任。 一、百年探索：昆虫细胞如何从实验室走向制药厂？ 昆虫细胞培养的故事，要从 100 多年前说起。1907 年，科学家哈里森成功在体外培养出动物细胞，开启了细胞培养的新时代。1915 年，戈德施密特首次将这种技术用到昆虫身上，成功培养出天蚕蛾的精子细胞，不过当时只能存活三周。 早期的昆虫细胞培养困难重重，没有合适的培养基、容易被细菌污染，根本无法长期存活。直到 1956 年，怀亚特研发出一种复杂的合成培养基，包含 20 多种氨基酸、无机盐和糖类，才让家蚕细胞得以正常生长分裂。真正的转折点出现在 1962 年，托马斯・格雷丝用 “粗放培养法”，意外获得了首个能连续传代的昆虫细胞系，还优化出至今仍在使用的培养基。 之后的几十年里，科学家们陆续开发出多种实用的昆虫细胞系。1977 年诞生的 Sf21 细胞系，因容易被病毒感染、增殖速度快，成为生产重组蛋白的 “主力军”；1983 年衍生出的 Sf9 细胞系，稳定性更优；1992 年发现的 High Five™细胞系，蛋白产量比 Sf9 还高 2 倍。如今，全球已建立超过 1500 种连续昆虫细胞系，其中 90% 都来自鳞翅目和双翅目昆虫。 图1 昆虫细胞培养发展里程碑二、核心技术：昆虫细胞如何 “变身” 蛋白生产机？ 昆虫细胞之所以能成为生物制药的核心工具，关键靠两种主流技术：杆状病毒表达载体系统（BEVS）和无病毒质粒转染系统。 BEVS 是目前最常用的技术，简单说就是 “借病毒送基因”。科学家把需要生产的蛋白基因（比如新冠病毒的刺突蛋白基因）插入杆状病毒，再用这种病毒感染昆虫细胞。病毒会带着目标基因进入细胞，利用细胞的 “生产设备” 大量合成目标蛋白。这种技术的优点很突出：杆状病毒对人类无害，生产的蛋白活性高，还能轻松放大规模。 为了提高效率，科学家还优化出 Bac-to-Bac 技术，把病毒载体的构建转移到大肠杆菌中完成，大幅缩短了制备时间。后来又开发出 flashBAC™、BestBac™等系统，通过删除病毒的无用基因，进一步提高蛋白产量，简化纯化流程。 无病毒质粒转染系统则更直接，跳过病毒载体，直接把含目标基因的质粒转入昆虫细胞。这种方法不用经历病毒感染步骤，蛋白纯化更简单，还能建立稳定的细胞系长期生产。不过它的蛋白表达量通常比 BEVS 低，更适合实验室研究或小批量生产。 图 2 重组蛋白生产系统对比 （图中 A 为基于 BEVS 的经典 Bac-to-Bac 系统，B 为无病毒质粒转染系统，B1 为稳定单克隆细胞系构建流程，清晰展示两种技术的生产步骤及时长差异） 值得一提的是，昆虫细胞还能生产病毒样颗粒（VLPs）—— 这种颗粒长得像病毒，却没有病毒的遗传物质，不会致病，是疫苗研发的 “黄金选择”。它能激发强烈的免疫反应，尤其适合应对流感、新冠这类变异快的病毒。三、技术升级：让昆虫细胞 “生产” 出更优质的蛋白 虽然昆虫细胞优势明显，但早期也有短板：比如蛋白的糖基化修饰和人类细胞有差异，可能影响药效；病毒感染后细胞会裂解，产生大量杂质，增加纯化难度。为了解决这些问题，科学家们做了不少技术升级。1. 优化蛋白修饰：让昆虫蛋白更 “像人” 糖基化是蛋白发挥功能的关键修饰。昆虫细胞生产的蛋白糖链比较简单，而人类蛋白的糖链更复杂。通过糖工程技术，科学家给昆虫细胞转入人类的糖基转移酶基因，让它能合成和人类细胞类似的糖链。如今，经过改造的 SfSWT 系列细胞系，已经能生产出接近人类蛋白的糖基化修饰产物。2. 延长细胞寿命：提高蛋白产量 病毒感染后，昆虫细胞会很快凋亡，限制了蛋白产量。科学家通过转入抗凋亡基因（比如 P35 基因、vankyrin 基因），或者沉默促凋亡基因（比如 caspase-1 基因），让细胞在感染后能存活更久，蛋白产量最高能提升 26 倍。3. 快速检测：缩短生产周期 传统的病毒滴度检测需要一周时间，影响生产效率。科学家开发出 Sf9-ET、Sf9-QE 等工程细胞系，这些细胞被病毒感染后会发出荧光，通过荧光就能快速判断病毒浓度，检测时间缩短到 3 天。4. 适应性进化：让细胞更 “抗压” 通过适应性实验室进化（ALE） 技术，让昆虫细胞在特定环境（比如高 pH、低温）下长期培养，筛选出适应性更强的细胞系。比如在 pH7.0-7.2 的环境中培养 Sf21 细胞，得到的 SfBasic 细胞系，生产基孔肯雅病毒样颗粒的产量提升了 11 倍；在 22℃低温下培养的细胞系，HIV 病毒样颗粒产量最高能增加 26 倍。 图 3 昆虫细胞优化策略汇总四、实际应用：昆虫细胞生产的药物就在我们身边 经过几十年的发展，昆虫细胞系已经实现了规模化应用，生产出多种获批的疫苗和药物，涵盖人类医疗和兽医领域。表1 已上市的昆虫细胞来源药物 其中最知名的就是新冠疫苗 Nuvaxovid®，它采用 Sf9 细胞系生产新冠病毒刺突蛋白，再组装成纳米颗粒疫苗，因技术成熟、安全性高，获得了多个国家的紧急使用授权。还有预防宫颈癌的 Cervarix™疫苗，利用昆虫细胞生产人乳头瘤病毒（HPV）的病毒样颗粒，已在全球广泛使用。 图4 Nuvaxovid 疫苗生产流程  除了新冠疫苗，预防宫颈癌的Cervarix™疫苗也是昆虫细胞的 “代表作”—— 它利用昆虫细胞生产人乳头瘤病毒（HPV）的 L1 衣壳蛋白，这些蛋白会自动组装成病毒样颗粒，接种后能精准激发针对 HPV16、18 型的免疫保护，这两种亚型正是导致宫颈癌的主要 “元凶”。 在兽医领域，昆虫细胞的贡献也不小。比如预防猪圆环病毒病的 Porcilis® PCV 疫苗，用昆虫细胞生产 PCV2 病毒的 ORF2 蛋白，制成的疫苗能有效降低猪群的发病率，帮养殖户减少经济损失；还有古典猪瘟疫苗 Porcilis Pesti®，同样靠昆虫细胞生产 E2 蛋白，在全球养猪业广泛使用。 除此之外，还有多款基于昆虫细胞的药物正在临床试验中，涵盖流感、埃博拉、寨卡病毒等传染病，以及疟疾、艾滋病等重大疾病，未来应用前景十分广阔。表2 临床试验中的昆虫细胞来源疫苗 五、未来展望：昆虫细胞的 “进化” 之路 目前，昆虫细胞系已经成为生物制药的重要平台，全球重组蛋白市场中，10% 的产品都来自昆虫细胞，这个市场规模预计到 2030 年将达到 55.8 亿美元。但它仍有进步空间：比如部分细胞系可能携带潜在病毒，需要进一步优化；大规模生产的成本还有下降空间；糖基化修饰还能更接近人类细胞。 未来，随着CRISPR/Cas9 基因编辑技术的深入应用，科学家有望精准改造昆虫细胞的基因，让它能生产出更复杂的蛋白；无病毒生产系统的效率会不断提升，逐步实现工业化应用；甚至可能利用昆虫幼虫作为 “活体工厂”，进一步降低生产成本。 从 100 多年前的初步尝试，到如今成为疫苗、抗癌药的核心生产工具，昆虫细胞系的发展堪称生物制药的 “逆袭之路”。这个藏在实验室里的 “昆虫工厂”，正在用科技的力量，为人类健康带来更多可能。相信在不久的将来，会有更多基于昆虫细胞的创新药物问世，守护我们的健康。 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。

Total revenue of $70 million in the third quarter of 2025 Continued successful execution of Sanofi partnership with $225 million in milestones achieved year-to-date including $50 million earned on marketing authorization transfers Sanofi reported preliminary positive immunogenicity and safety Phase 1/2 data for Nuvaxovid ™ in combination with both Fluzone High-Dose and Flublok Sanofi received BARDA grant for pandemic influenza vaccine candidate using Novavax's Matrix-M® adjuvant Maryland site consolidation transactions resulted in $60 million cash proceeds and approximately $230 million in expected future cost savings Raises Full Year 2025 Revenue Framework and Affirms Financial Guidance C ompany to host conference call today at 8:30 a.m. ET GAITHERSBURG, Md., Nov. 6, 2025 /PRNewswire/ -- Novavax, Inc. (Nasdaq: NVAX) today announced its financial results and operational highlights for the third quarter ended September 30, 2025. "We have continued the steady transformation of Novavax and are proud of our progress this quarter," said John C. Jacobs, President and Chief Executive Officer, Novavax. "This year we have relaunched the Company with a focus on R&D and partnerships intended to position us well for long-term growth and profitability." Third Quarter 2025 and Recent Highlights Key Highlights Strategic Priority #1: Optimize our Sanofi Partnership Continued successful execution of Sanofi partnership with $225 million in milestones earned year-to-date, including $50 million earned in the fourth quarter of 2025, upon marketing authorization transfers for E.U. and U.S. markets. In October 2025, Sanofi reported preliminary positive immunogenicity and safety Phase 1/2 data for Nuvaxovid™ in combination with both Fluzone High-Dose and Flublok. Both programs have received Fast Track designation from the U.S. Food and Drug Administration (FDA). In August 2025, the FDA approved the Nuvaxovid 2025-2026 Formula for the prevention of COVID-19 in individuals 65 years of age and older, or 12 years through 64 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19. Nuvaxovid was approved with an extended shelf life of six months in a pre-filled syringe formulation. Beginning in the third quarter of 2025, Sanofi assumed the lead commercial role for Nuvaxovid in the U.S. and select ex-U.S. markets for the 2025-2026 COVID-19 vaccination season. In September 2025, Novavax expanded Sanofi's license to include use of Novavax's Matrix-M® adjuvant in Sanofi's pandemic influenza vaccine candidate program. Sanofi received funding from the Biomedical Advanced Research and Development Authority (BARDA) for early-stage clinical work on this vaccine candidate. Strategic Priority #2: Enhance Existing Partnerships and Leverage our Technology Platform and Pipeline to Forge Additional Partnerships In September 2025, our partner Takeda received approval of Nuvaxovid in Japan which triggered a milestone payment to Novavax. 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 25 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; discussions continue with these companies for the potential use of Matrix-M in the development of new vaccines and/or improve existing vaccines. Strategic Priority #3: Advance our Technology Platform and Early-Stage Pipeline Continued advancement of early-stage preclinical research for varicella-zoster virus (shingles), Clostridioides difficile colitis and respiratory syncytial virus combinations vaccine candidates. Pursuing government funding for pandemic influenza vaccine candidate. Continued exploration of our Matrix-M platform technology in oncology. Other Corporate Highlights In August 2025, Novavax completed a convertible debt refinancing; extending the maturity of the majority of the Company's existing 2027 Notes to 2031, with improved terms, and providing additional proceeds through the issuance of new 2031 Notes. This transaction further supports the financial strength of the company and its ability to execute on its long-term growth strategy. In October 2025, Novavax announced transactions to enable the planned consolidation of its Maryland based facilities in line with its corporate strategy. These transactions will result in $60 million in payments to Novavax and are expected to result in future cost savings of approximately $230 million over 11 years. Third Quarter 2025 Revenue Third Quarter 2025 Financial Results Total revenue for the third quarter of 2025 was $70 million, compared to $85 million in the same period in 2024. Cost of sales for the third quarter of 2025 was $21 million, compared to $61 million in the same period in 2024. Research and development (R&D) expenses for the third quarter of 2025 were $98 million, compared to $87 million in the same period in 2024. R&D transition services expenses reimbursed by Sanofi in the third quarter of 2025 were $46 million or approximately 47% of total R&D expenses in the period. Selling, general, and administrative (SG &A) expenses for the third quarter of 2025 were $32 million, compared to $71 million for the same period in 2024. The 55% 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. Non-cash charges for the third quarter of 2025 were $126 million. The $97 million asset impairment related to the Maryland site consolidation transactions announced in October 2025, which includes the write off of the right-of-use asset, property and equipment, and intangibles, partially offset by a gain recognized on the sale of adjacent land. The $29 million loss on debt extinguishment related to the August 2025 convertible debt refinancing. Net loss for the third quarter of 2025 was $202 million, compared to net loss of $121 million in the same period in 2024. Cash, cash equivalents, marketable securities and restricted cash (Cash) were $778 million as of September 30, 2025, compared to $938 million as of December 31, 2024. Financial Framework Full Year 2025 Financial Guidance Novavax provides Full Year 2025 Financial Guidance for Combined R&D and SG&A Expenses and Non-GAAP Combined R&D and SG&A Expenses and currently expects to achieve the following results: Non-GAAP Combined R&D and SG&A Expenses exclude R&D Reimbursements, which are amounts reimbursed by Novavax's license partners. See "Non-GAAP Financial Measures" below. R&D Reimbursements are recorded as revenue under Licensing, Royalties and Other Revenue. 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 $1,040 million and $1,060 million. 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 November 6, 2025, until 11:59 p.m. ET on November 13, 2025. To access the replay by telephone, dial (800) 770-2030 (Domestic) or (+1) (609) 800-9909 (International) and use passcode 3585070#. 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 December 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: Non-GAAP Combined R&D and SG&A Expenses, 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 revenue 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 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, conducted by Novavax or its partners, and other preclinical and postmarketing studies; expectations as to the timing and outcome of future and pending regulatory filings and actions; expected savings from Maryland site consolidation transactions; full year 2025 financial guidance and revenue framework; 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 , 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 Yvonne Sprow 844-264-8571 [email protected] SOURCE Novavax, Inc. 21% more press release views with Request a Demo