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更新于：2025-07-31

Influenza vaccine(Seqirus GmbH)

更新于：2025-07-31

概要

概要

基本信息

药物类型

灭活疫苗、预防性疫苗

别名

influenza vaccine (surface antigen, inactivated, prepared in cell cultures)、influenza virus surface antigens (haemagglutinin and neuraminidase), inactivated, of the following strains:A/California/7/2009 (H1N1)pdm09 - like strain(A/Brisbane/10/2010, wild type)A/Switzerland/9715293/2013 (H3N2) - like strain(A/South Australia/55/2014, wild type)B/Phuket/3073/2013–like strain(B/Utah/9/2014, wild type)、influenza virus surface antigens (haemagglutinin and neuraminidase), inactivated, of the following strains:A/California/7/2009 (H1N1)pdm09-like strain(A/Brisbane/10/2010, wild type)A/Switzerland/9715293/2013 (H3N2)-like strain(A/South Australia/55/2014, wild type)B/Phuket/3073/2013-like strain(B/Utah/9/2014, wild type)

+ [2]

靶点-

作用方式

刺激剂

作用机制

免疫刺激剂

治疗领域

感染呼吸系统疾病

在研适应症

甲型流感病毒感染乙型流感病毒感染流感病毒感染

非在研适应症-

原研机构

Seqirus GmbH

在研机构

Seqirus GmbHSeqirus Netherlands BV

Seqirus UK Ltd.

+ [1]

非在研机构

Novartis AGNovartis Pharma AG

权益机构

Seqirus Inc

Emergent Travel Health, Inc.

最高研发阶段批准上市

首次获批日期

澳大利亚 (2002-10-15),

流感病毒感染

最高研发阶段(中国)-

特殊审评-

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关联

项与 Influenza vaccine(Seqirus GmbH) 相关的临床试验

NCT05291676

/ Recruiting临床2期IIT

Systems Investigation of Vaccine Responses in Aging and Frailty

This study will compare the immune response signatures (including immunologic, transcriptomic and metabolomic) of the two influenza vaccines approved for use in adults age 65 and over (Fluad and Fluzone High-Dose).

开始日期2023-11-06

申办/合作机构

Yale University

[+1]

NCT06029933

/ RecruitingN/A

Relative Vaccine Effectiveness of Adjuvanted Quadrivalent Inactivated Influenza Vaccine vs High-Dose Quadrivalent Inactivated Influenza Vaccine Among Adults ≥65 Years for the 2023-24 and 2024-25 Seasons

This study will evaluate the relative vaccine effectiveness of quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) versus quadrivalent high-dose inactivated influenza vaccine (HD-IIV4) in preventing polymerase chain reaction (PCR)-confirmed influenza and influenza-related outcomes in adults ≥65 years of age during the 2023/24 and 2024/25 influenza seasons. The study is an observational study conducted at Kaiser Permanente Northern California (KPNC), an integrated health care system in the United States.

开始日期2023-08-17

申办/合作机构

Kaiser Permanente, Inc.

[+1]

NCT04101838

/ Recruiting临床4期IIT

B Cell and Antibody Response to Seasonal Influenza Vaccines in Younger and Older Adults

This study will examine how various FDA-approved seasonal influenza vaccine types, used in a manner consistent with their approved use, impact the characteristics of influenza specific antibodies in humans, and how these responses differ based on age and prior immunization history.

开始日期2021-04-01

申办/合作机构

The University of Alabama at Birmingham

100 项与 Influenza vaccine(Seqirus GmbH) 相关的临床结果

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100 项与 Influenza vaccine(Seqirus GmbH) 相关的转化医学

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100 项与 Influenza vaccine(Seqirus GmbH) 相关的专利（医药）

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103

项与 Influenza vaccine(Seqirus GmbH) 相关的文献（医药）

2025-07-01·Journal of the American Medical Directors Association

Which Enhanced Influenza Vaccine Has the Greatest Immunogenicity in Long-Term Care Residents: The Adjuvanted or the High-Dose Formulation?

Article

作者: Wilson, Brigid M ; Buss, Emily ; Didion, Elise M ; Wilk, Dennis J ; Kass, Joseph D ; Canaday, David H ; Frischmann, Sarah-Michelle ; Banks, Richard ; Gravenstein, Stefan ; Rubeck, Sabina

OBJECTIVES:

This study compares enhanced influenza vaccines recommended for older adults, adjuvanted flu vaccine (aTIV, FLUAD) vs high-dose flu vaccine (HD-IIV3, FLUZONE HD) to determine if they met noninferiority standards for older long-term care facility (LTCF) residents.

DESIGN:

A phase 4, randomized, active-controlled, noninferiority trial on influenza vaccine immunogenicity conducted over 2 influenza seasons (2018-2019 and 2019-2020) (NCT03694808).

SETTING AND PARTICIPANTS:

Residents of LTCFs aged ≥65 years.

METHODS:

Participants were randomized 1:1 to receive either aTIV or HD-IIV3 using computer-generated randomization. Only laboratory personnel were blinded. Hemagglutination inhibition (HAI) and neuraminidase inhibition (NI) assays measured antibody responses at baseline and 28 days postvaccination. The primary outcome compared the geometric mean titers (GMTs) at day 28. Secondary outcomes included seroconversion rates and NI titers.

RESULTS:

We randomized 387 LTCF residents to receive either aTIV (n = 194) or HD-IIV3 (n = 193) over 2 flu seasons. We observed noninferior HAI levels at postvaccination day 28 to A/H1N1 and A/H3N2 for aTIV and HD-IIV3 (GMT ratio, 1.03; 95% CI, 0.76-1.4; and GMT ratio, 1.04; 95% CI, 0.73-1.48, respectively), meeting noninferiority criteria with 95% CI upper bounds <1.5. However, noninferiority criteria were not met for influenza B HAI levels (GMT ratio, 1.21; 95% CI, 0.91-1.61). Also, noninferiority criteria for HAI seroconversion were not met for any of the 3 strains. Applying the same noninferiority criteria to NI, both day 28 titer and seroconversion in aTIV were noninferior to HD-IIV3 for A/H1N1 and A/H3N2 strains.

CONCLUSIONS AND IMPLICATIONS:

Overall the anti-hemagglutinin and anti-neuraminidase titers demonstrate similarities between the vaccines and support them both being in the enhanced flu vaccine category preferentially recommended by the Centers for Disease Control and Prevention for people aged ≥65 years.

2025-02-01·Lancet Microbe

Molecular features of the serological IgG repertoire elicited by egg-based, cell-based, or recombinant haemagglutinin-based seasonal influenza vaccines: a comparative, prospective, observational cohort study

Article

作者: Bartzoka, Foteini ; Sambhara, Suryaprakash ; Kain, Jessica ; Thompson, Mark G ; Liu, Feng ; Gangappa, Shivaprakash ; Kennedy, Richard B ; Jacob, Joshy ; Cao, Weiping ; Schwartz, Evan A ; von Beck, Troy ; McKnight, Eric ; Satterwhite, Ed ; Kim, Jin Eyun ; Towers, Dalton M ; Sharma, Suresh ; Park, Juyeon ; Stevens, James ; Lee, Justin S ; Brilot, Axel F ; Gaglani, Manjusha ; Kumar, Amrita ; Hebert, Luke S ; Levine, Min Z ; Naleway, Allison L ; Ippolito, Gregory C ; Wang, Yuanyuan ; Lavinder, Jason J ; Eddins, Devon J ; Dawood, Fatimah S ; Pohl, Jan ; Georgiou, George ; Mishina, Margarita ; Li, Zhu-Nan

BACKGROUND:

Egg-based inactivated quadrivalent seasonal influenza vaccine (eIIV4), cell culture-based inactivated quadrivalent seasonal influenza vaccine (ccIIV4), and recombinant haemagglutinin (HA)-based quadrivalent seasonal influenza vaccine (RIV4) have been licensed for use in the USA. In this study, we used antigen-specific serum proteomics analysis to assess how the molecular composition and qualities of the serological antibody repertoires differ after seasonal influenza immunisation by each of the three vaccines and how different vaccination platforms affect the HA binding affinity and breadth of the serum antibodies that comprise the polyclonal response.

METHODS:

In this comparative, prospective, observational cohort study, we included female US health-care personnel (mean age 47·6 years [SD 8]) who received a single dose of RIV4, eIIV4, or ccIIV4 during the 2018-19 influenza season at Baylor Scott & White Health (Temple, TX, USA). Eligible individuals were selected based on comparable day 28 serum microneutralisation titres and similar vaccination history. Laboratory investigators were blinded to assignment until testing was completed. The preplanned exploratory endpoints were assessed by deconvoluting the serological repertoire specific to A/Singapore/INFIMH-16-0019/2016 (H3N2) HA before (day 0) and after (day 28) immunisation using bottom-up liquid chromatography-mass spectrometry proteomics (referred to as Ig-Seq) and natively paired variable heavy chain-variable light chain high-throughput B-cell receptor sequencing (referred to as BCR-Seq). Features of the antigen-specific serological repertoire at day 0 and day 28 for the three vaccine groups were compared. Antibodies identified with high confidence in sera were recombinantly expressed and characterised in depth to determine the binding affinity and breadth to time-ordered H3 HA proteins.

FINDINGS:

During September and October of the 2018-19 influenza season, 15 individuals were recruited and assigned to receive RIV4 (n=5), eIIV4 (n=5), or ccIIV4 (n=5). For all three cohorts, the serum antibody repertoire was dominated by back-boosted antibody lineages (median 98% [95% CI 88-99]) that were present in the serum before vaccination. Although vaccine platform-dependent differences were not evident in the repertoire diversity, somatic hypermutation, or heavy chain complementarity determining region 3 biochemical features, antibodies boosted by RIV4 showed substantially higher binding affinity to the vaccine H3/HA (median half-maximal effective concentration [EC50] to A/Singapore/INFIMH-16-0019/2016 HA: 0·037 μg/mL [95% CI 0·012-0·12] for RIV4; 4·43 μg/mL [0·030-100·0] for eIIV4; and 18·50 μg/mL [0·99-100·0] μg/mL for ccIIV4) and also the HAs from contemporary H3N2 strains than did those elicited by eIIV4 or ccIIV4 (median EC50 to A/Texas/50/2012 HA: 0·037 μg/mL [0·017-0·32] for RIV4; 1·10 μg/mL [0·045-100] for eIIV4; and 12·6 μg/mL [1·8-100] for ccIIV4). Comparison of B-cell receptor sequencing repertoires on day 7 showed that eIIV4 increased the median frequency of canonical egg glycan-targeting B cells (0·20% [95% CI 0·067-0·37] for eIIV4; 0·058% [0·050-0·11] for RIV4; and 0·035% [0-0·062] for ccIIV4), whereas RIV4 vaccination decreased the median frequency of B-cell receptors displaying stereotypical features associated with membrane proximal anchor-targeting antibodies (0·062% [95% CI 0-0·084] for RIV4; 0·12% [0·066-0·16] for eIIV4; and 0·18% [0·016-0·20] for ccIIV4). In exploratory analysis, we characterised the structure of a highly abundant monoclonal antibody that binds to both group 1 and 2 HAs and recognises the HA trimer interface, despite its sequence resembling the stereotypical sequence motif found in membrane-proximal anchor binding antibodies.

INTERPRETATION:

Although all three licensed seasonal influenza vaccines elicit serological antibody repertoires with indistinguishable features shaped by heavy imprinting, the RIV4 vaccine selectively boosts higher affinity monoclonal antibodies to contemporary strains and elicits greater serum binding potency and breadth, possibly as a consequence of the multivalent structural features of the HA immunogen in this vaccine formulation. Collectively, our findings show advantages of RIV4 vaccines and more generally highlight the benefits of multivalent HA immunogens in promoting higher affinity serum antibody responses.

FUNDING:

Centers for Disease Control and Prevention, National Institutes of Health, and Bill & Melinda Gates Foundation.

2024-09-27·Science Advances

Systemic dysregulation and molecular insights into poor influenza vaccine response in the aging population

Article

作者: Graca, Luis ; Arshad, Haroon ; Guzmán, Carlos A. ; Zoodsma, Martijn ; Pessler, Frank ; Kumar, Saumya ; Trittel, Stephanie ; Riese, Peggy ; Netea, Mihai G. ; Alaswad, Ahmed ; Xu, Cheng-Jian ; Li, Yang ; Botey-Bataller, Javier ; Pedroso, Rodrigo ; Nguyen, Nhan ; Zhou, Liang

Vaccination-induced protection against influenza is greatly diminished and increasingly heterogeneous with age. We investigated longitudinally (up to five time points) a cohort of 234 vaccinated >65-year-old vaccinees with adjuvanted vaccine FluAd across two independent seasons. System-level analyses of multiomics datasets measuring six modalities and serological data revealed that poor responders lacked time-dependent changes in response to vaccination as observed in responders, suggestive of systemic dysregulation in poor responders. Multiomics integration revealed key molecules and their likely role in vaccination response. High prevaccination plasma interleukin-15 (IL-15) concentrations negatively associated with antibody production, further supported by experimental validation in mice revealing an IL-15–driven natural killer cell axis explaining the suppressive role in vaccine-induced antibody production as observed in poor responders. We propose a subset of long-chain fatty acids as modulators of persistent inflammation in poor responders. Our findings provide a potential link between low-grade chronic inflammation and poor vaccination response and open avenues for possible pharmacological interventions to enhance vaccine responses.

项与 Influenza vaccine(Seqirus GmbH) 相关的新闻（医药）

2025-07-26

·生物制品圈

重组蛋白亚单位疫苗：不依赖鸡胚仅具有单一目标抗原的流感疫苗

摘要：流感病毒引发的季节性流行和大流行对全球公共卫生构成持续威胁，开发安全有效的疫苗是防控流感的关键手段。本文系统介绍了甲型流感病毒的结构、生命周期及重大流行历史，对比了不同类型流感疫苗的优缺点，重点阐述了亚单位疫苗的研发进展，包括基于核蛋白（NP）、基质蛋白 2 胞外域（M2e）和血凝素（HA）的亚单位疫苗的设计原理、免疫机制及优化策略。文章还总结了处于临床试验阶段和已获批的流感疫苗，分析了亚单位疫苗的优势与挑战，并展望了未来发展方向。亚单位疫苗凭借高安全性、可规模化生产等特点，成为应对流感大流行的重要候选，尤其是基于保守抗原的通用疫苗研发为长期防控流感提供了新希望。一、流感病毒的生物学特性与流行威胁1.1 病毒结构与生命周期甲型流感病毒属于正黏病毒科，其基因组由 8 条单链负链 RNA 片段组成，编码 11 种蛋白质，包括结构蛋白（血凝素 HA、神经氨酸酶 NA、基质蛋白 M1、离子通道蛋白 M2、核蛋白 NP）、RNA 聚合酶（PB1、PB2、PA）及非结构蛋白（NS1、NS2、PB1-F2）（图 1）。HA：病毒表面的刺突蛋白，负责识别宿主细胞表面的唾液酸受体，介导病毒入侵，是诱导中和抗体的主要靶标。NA：通过切割唾液酸残基帮助子代病毒释放，是抗流感药物（如奥司他韦）的作用靶点。M2：形成跨膜离子通道，在病毒脱壳过程中调节 pH，对病毒复制至关重要。NP：包裹病毒 RNA，维持基因组稳定性，是诱导 T 细胞免疫的关键抗原。流感病毒的生命周期涉及多个步骤（图 2）：首先通过 HA 结合宿主细胞表面的唾液酸受体，经内吞作用进入细胞；在酸性内体环境中，HA 发生构象变化，介导病毒膜与内体膜融合，同时 M2 离子通道激活，促进病毒核衣壳释放到细胞质；病毒 RNA 进入细胞核后进行转录和复制，合成的病毒蛋白与 RNA 组装成新的核衣壳，通过 NS2 介导的核输出转运至细胞膜；最后，病毒在细胞膜处组装并释放，NA 通过清除唾液酸残基防止病毒聚集，促进其扩散。1.2 重大流感大流行历史流感病毒的抗原漂移（基因突变）和抗原转变（基因重配）是引发流行和大流行的主要原因。20 世纪以来，全球发生多次重大流感大流行：1918 年西班牙流感（H1N1）：最严重的流感大流行，全球约 5000 万人死亡，病毒可能源自禽类，通过抗原转变获得人际传播能力。1957 年亚洲流感（H2N2）：由 H2N2 亚型引起，源于禽流感病毒与人类流感病毒的基因重配，导致约 100 万人死亡。1968 年香港流感（H3N2）：H3N2 亚型通过基因重配产生，致死人数约 70 万，因保留了 NA 蛋白，致病性较 1918 年病毒温和。2009 年甲型 H1N1 流感：源自猪流感病毒的基因重配，在全球范围内快速传播，确诊病例超 29.6 万，死亡 3400 人。2013 年 H7N9 禽流感：首次在人类中发现，截至 2014 年 6 月报告 450 例，死亡 165 人，虽未形成持续人际传播，但仍具大流行潜力。此外，高致病性 H5N1 禽流感自 1997 年首次感染人类以来，累计报告 667 例，死亡率近 60%，其在禽类中的持续流行对人类健康构成长期威胁。二、流感疫苗的类型与特点目前已开发的流感疫苗主要包括灭活疫苗、减毒活疫苗、DNA 疫苗、病毒载体疫苗、病毒样颗粒（VLP）疫苗和亚单位疫苗，各类疫苗的优缺点及所用佐剂如下表所示：表 1 不同类型流感疫苗的特点比较疫苗类型优势劣势所用佐剂灭活疫苗和减毒活疫苗诱导强效体液和细胞免疫，保护效果明确存在安全隐患（如基因重配风险），鸡蛋培养可能引发过敏rintatolimod、MF59、AS03BDNA 疫苗安全性高，易于规模化生产，可优化基因序列免疫原性低，可能诱发自身免疫或恶性肿瘤风险无病毒载体疫苗诱导高强度体液和细胞免疫，交叉保护力强存在安全风险，预存免疫力可能降低效果无VLP 疫苗无基因组，仅含病毒包膜蛋白，安全性高免疫原性相对较低无亚单位疫苗安全性最高（无感染性病毒），生产稳定可规模化，诱导特异性免疫需佐剂或优化策略增强免疫原性可与抗原融合或混合使用M2e 亚单位疫苗诱导交叉保护，潜力开发为通用疫苗单一 M2e 免疫原性低，需多拷贝或载体融合Iscomatrix、明矾、弗氏佐剂NP 亚单位疫苗含保守 T 细胞表位，诱导交叉保护诱导中和抗体能力弱明矾、Ribi 佐剂系统HA 亚单位疫苗诱导强效中和抗体，保护效果好，HA2 茎部可开发通用疫苗HA1 易变异，诱导株特异性保护PELC/CpG、弗氏佐剂、CpG7909NA 亚单位疫苗诱导针对同源病毒的保护交叉保护力弱Iscomatrix灭活疫苗和减毒活疫苗：传统疫苗类型，应用广泛，但存在基因重配风险，且鸡蛋培养可能引发过敏。DNA 疫苗：通过编码病毒抗原的质粒诱导免疫，安全性高但免疫原性不足，在老年人和新生儿中效果较差。病毒载体疫苗：利用腺病毒等载体表达流感抗原，免疫原性强，但预存抗体可能影响效果。VLP 疫苗：由病毒结构蛋白组装而成，无传染性，可诱导有效免疫，但免疫原性需提升。亚单位疫苗：基于病毒单个或多个抗原蛋白（如 HA、M2e、NP），安全性最高，是应对大流行的理想选择，但需佐剂或设计优化增强免疫原性。三、流感亚单位疫苗的研发进展亚单位疫苗以病毒特定抗原为核心，避免了完整病毒带来的安全风险，且生产过程稳定可控，成为近年来的研发热点。目前重点研究的抗原包括 M2e、NP 和 HA。鸡胚“亚单位”VS杆状病毒重组亚单位流感疫苗：一场“真假亚单位”的科学审视3.1 基于 M2e 的亚单位疫苗M2e 是基质蛋白 M2 的胞外域，含 24 个氨基酸，在甲型流感病毒中高度保守（N 端 8 个氨基酸同源性近 100%），是开发通用流感疫苗的理想靶标。但单一 M2e 分子免疫原性低，需通过以下策略优化：多拷贝串联：将多个 M2e 序列串联表达，如大肠杆菌表达的串联 M2e 蛋白在鸡中对 H5N1 病毒的保护效果显著提升。载体融合：与多抗原肽（MAP）、布鲁氏菌荧光素酶（BLS）等载体融合，增强免疫原性。例如，BLS-4M2e 融合蛋白在小鼠中诱导的存活率达 100%（含佐剂）或 60%（无佐剂）。佐剂融合：将 M2e 与免疫激活蛋白（如 ASP-1）融合，无需额外佐剂即可诱导交叉保护。研究显示，M2e3-ASP-1 融合蛋白可保护小鼠抵御不同亚型 H5N1 病毒的攻击。3.2 基于 NP 的亚单位疫苗NP 是流感病毒中最保守的蛋白之一，含多个 CD8⁺T 细胞表位，可诱导交叉反应性 T 细胞免疫，为开发通用疫苗提供可能。免疫机制：NP 主要通过激活 CD4⁺和 CD8⁺T 细胞清除感染细胞，虽诱导中和抗体能力弱，但可减轻疾病严重程度。优化策略：与佐剂（如 Ribi 佐剂系统）联合使用可增强体液和细胞免疫。例如，NP 加 Ribi 佐剂在小鼠中诱导的免疫应答显著高于未加佐剂组。3.3 基于 HA 的亚单位疫苗HA 是诱导保护性免疫的关键抗原，其诱导的中和抗体可有效阻断病毒入侵，是目前亚单位疫苗的主要靶标。HA1 片段：含受体结合位点，诱导中和抗体能力强，但易变异，主要提供株特异性保护。通过聚糖修饰或关键中和域（CND）设计可增强交叉保护。例如，HA1-Fdc 融合蛋白（含 Fc 和三聚化基序）可诱导对不同 H5N1 毒株的交叉中和。HA2 片段：较 HA1 保守，尤其是茎部区域，可诱导广谱交叉保护。研究显示，HA2 肽疫苗可保护小鼠抵御 H1N1、H3N2 和 H5N1 病毒感染，是通用疫苗的重要候选。3.4 其他亚单位疫苗M1 疫苗：基质蛋白 M1 诱导的免疫可提供一定交叉保护，如大肠杆菌表达的 M1 蛋白加壳聚糖佐剂对 H9N2、H1N1 和 H5N1 病毒的保护率分别为 100%、70% 和 30%。NA 疫苗：传统认为交叉保护力弱，但近年发现 NA 保守表位可诱导跨亚型保护，如抗 NA 单克隆抗体可抑制所有甲型流感亚型，为多组分亚单位疫苗设计提供思路。四、亚单位疫苗的优化策略为提升亚单位疫苗的免疫原性和保护效果，研究人员开发了多种优化策略：4.1 佐剂应用佐剂可显著增强亚单位疫苗的免疫应答：皂苷类佐剂（如 GPI-0100）：增强黏膜免疫，提升 HA 疫苗的黏膜 IgA 和血清 IgG 水平。CpG 寡核苷酸：激活 TLR9，增强 Th1 型免疫应答，与 HA 疫苗联合使用可提高中和抗体滴度。重组霍乱毒素 B 亚单位（rCTB）：增强黏膜免疫，鼻内接种时可显著提升 HA 特异性 IgA 和 IgG 水平。4.2 抗原设计优化多抗原融合：将不同抗原（如 HA1 与呼吸道合胞病毒 G 蛋白片段）融合，诱导针对多种病原体的免疫。结构优化：通过三聚化基序（如 foldon）维持 HA 的天然构象，增强中和抗体诱导能力。4.3 免疫途径与策略黏膜免疫：舌下或鼻内接种可诱导局部 IgA 应答，与肌肉注射效果相当且更易接受。prime-boost 策略：DNA 初免 - 蛋白加强可增强 NP 诱导的交叉保护；鼻内初免 - 肌肉加强联合佐剂可优化系统和黏膜免疫。五、临床试验与已获批疫苗目前多种流感疫苗处于临床试验阶段，部分已获批准应用：表 2 部分流感疫苗的临床试验阶段疫苗名称类型抗原成分阶段A/Shanghai/2/13(H7N9)灭活疫苗H7N9 HAII 期A/Indonesia/5/05(H5N1)灭活疫苗H5N1 HAII/III 期MVA-H5-sfMR病毒载体疫苗H5N1 HAI/IIa 期MVA-NP＋M1病毒载体疫苗H3N2 NP 和 M1I 期gH1-QbetaVLP 疫苗2009H1N1 HAI 期HAC1亚单位疫苗2009H1N1 HAI 期HAI-05亚单位疫苗H5N1 HAI 期已获批疫苗：Aflunov：MF59 佐剂的 H5N1 灭活疫苗，对同源和异源毒株均有免疫原性，适用于各年龄组。Flublok：美国 FDA 批准的首个重组亚单位疫苗，基于昆虫细胞表达的 HA 蛋白，可快速规模化生产，为应对大流行提供保障。亚单位疫苗优势：在临床试验中表现出良好的安全性和免疫原性，如植物表达的 HAC1 疫苗在健康成人中诱导中和抗体应答，HAI-05 疫苗在 18-49 岁成人中安全且能诱导抗 H5N1 免疫。六、总结与展望流感亚单位疫苗凭借高安全性、生产稳定性和可扩展性，成为应对流感大流行的重要手段。基于 M2e、NP 和 HA2 保守区域的通用疫苗研发取得显著进展，有望突破传统疫苗株特异性保护的局限。未来研究需聚焦以下方向：通用疫苗开发：利用保守抗原设计可覆盖多种亚型的疫苗，减少每年更新疫苗的需求。新型佐剂与递送系统：开发高效低毒佐剂，优化黏膜递送途径，提升免疫原性和依从性。多组分疫苗设计：联合 HA、NA、M2e 等抗原，诱导全面免疫应答，增强交叉保护。快速响应技术：完善重组蛋白生产平台，实现大流行期间的快速量产。流感疫苗的制备工艺在技术路径上存在显著差异，其核心源于病毒结构特性与生产技术的适配性。传统鸡胚培养工艺制备的流感疫苗面临多重技术瓶颈：首先，流感病毒粒子包含血凝素（HA）、神经氨酸酶（NA）及核蛋白（NP）等多种结构蛋白，其中 HA 分子量约 75-80kDa，NA 约 55-60kDa，NP 约 56kDa，这种分子量的趋近性导致常规层析纯化技术难以实现有效分离；其次，鸡胚培养体系会引入宿主特异性糖基化修饰，可能改变病毒蛋白的免疫原性特征；再者，病毒复制过程中产生的缺陷干扰颗粒（DI 颗粒）会形成多组分共存的复杂体系。这些因素共同导致传统工艺无法获得单一抗原成分的疫苗产品。与之形成鲜明对比的是，基于重组 DNA 技术的亚单位疫苗制备平台展现出显著技术优势：该技术通过基因工程将编码 HA 蛋白的 cDNA 片段克隆至杆状病毒表达载体，利用昆虫细胞培养系统进行表达；通过优化信号肽序列和糖基化修饰位点，实现 HA 蛋白的分泌型表达；采用亲和层析与离子交换层析联用技术，可获得纯度＞95% 的 HA 蛋白制剂。这种生产模式不仅规避了鸡胚适应性突变风险，还能通过模块化设计快速应对病毒变异。目前，该技术平台已成功应用于 H5N1 禽流感疫苗（Flucelvax®）及 H1N1 大流行疫苗（XBB.1.5）的生产，其诱导的中和抗体效价可达鸡胚疫苗的 1.5-2 倍，显示出更高的免疫保护效率。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。

疫苗核酸药物

2025-07-23

·FiercePharma

RFK Jr. rubber-stamps ACIP recommendation to remove thimerosal from all vaccines in US

Department of Health and Human Services Secretary Robert F. Kennedy Jr. has endorsed a Centers for Disease Control and Prevention advisory committee recommendation banning the use of thimerosal in all vaccines in the U.S. RFK Jr. and other anti-vaccine activists have said that the preservative, which contains mercury, can cause autism, while studies have shown no link. Department of Health and Human Services (HHS) Secretary Robert F. Kennedy Jr. has signed off on a Centers for Disease Control and Prevention (CDC) advisory committee recommendation to remove the preservative thimerosal from all flu shots distributed in the U.S.Thimerosal, which contains mercury, has been used in vaccines for nearly a century to prevent fungal or bacterial contamination after one dose has been drawn from a multidose vial.In 1999, the HHS, the American Academy of Pediatrics and vaccine manufacturers agreed that thimerosal should be reduced or eliminated in vaccines as a precautionary measure. Two years later, the U.S. recommended that children age 6 and younger not receive vaccines that contain thimerosal.Anti-vaccine activists have claimed that the preservative can cause autism, though multiple studies, including one by the CDC in 2010, have shown that there is no link.Last month, RFK Jr.’s revamped Advisory Committee on Immunization Practices (ACIP) recommended against the use of thimerosal in flu shots. In three separate rounds of voting, the ACIP advised that children, pregnant women and adults should not receive vaccines that contain thimerosal. Each of the votes were 5-1 in favor of removing thimerosal from vaccines, with one committee member abstaining.“After more than two decades of delay, this action fulfills a long-overdue promise to protect our most vulnerable populations from unnecessary mercury exposure,” RFK Jr. said in a release. “Injecting any amount of mercury into children when safe, mercury-free alternatives exist defies common sense and public health responsibility. Today, we put safety first.”Most companies have already removed the preservative from their vaccines. The exceptions are Sanofi, which produces multidose vials of Fluzone in addition to single-dose syringes, and CSL Seqirus, which includes thimerosal in its multidose vials of Afluria and Flucelvax. Each of these flu shots include a 0.01% concentration of thimerosal.“We acknowledge the recommendation of the new (ACIP),” a Sanofi spokesperson said in a brief statement. “We will have sufficient supply of Sanofi flu vaccine to support customer preference for this season.”Meanwhile, a spokesperson from CSL Seqirus said that “delivery of our thimerosal-free flu vaccines for the upcoming season is already underway and we don't expect the ACIP recommendation to have any impact on our vaccine supply or shipment timings." Both companies have said that they provide many more flu shots in single-dose syringes, which don’t contain thimerosal, than they do in multidose vials.Last month, during the ACIP meeting, Tracy Beth Hoeg, M.D., Ph.D., of the FDA, told the committee that fewer than 5% of the flu vaccines administered in the 2024-25 season contained thimerosal.While the decision does not have a major impact on the industry, it does raise concern about the influence of RFK Jr. and his hand-picked panel of ACIP experts, many of whom have expressed anti-vaccine views. Early last month, RFK Jr. dismissed all 17 previous members of the committee. In placing the lone dissenting vote in the ACIP meeting, Cody Meissner, M.D., of Dartmouth’s Geisel School of Medicine, said the "risk from influenza is so much greater than the nonexistent—as far as we know—risk from thimerosal."“I would hate for a person not to receive the influenza vaccine because the only available preparation contains thimerosal. I find that very hard to justify,” Meissner added.Meanwhile, with his decision, RFK Jr. urged "global health authorities to follow this prudent example for the protection of children worldwide."

疫苗

2025-07-21

·生物制品圈

联合疫苗困局：Moderna 撤市后行业陷入观望

摘要：Moderna 近日宣布撤回其新冠 - 流感联合疫苗 mRNA-1083 的上市申请，引发行业对多病毒联合疫苗前景的广泛讨论。这一决策不仅暴露了联合疫苗研发的技术挑战，更折射出监管标准模糊、市场需求波动等多重困境。目前辉瑞 / BioNTech、GSK 等企业的同类产品仍在推进，但 Moderna 的折戟已让联合疫苗赛道蒙上阴影。一、撤回背后：数据短板与监管压力的双重暴击Moderna 在声明中称，撤回 mRNA-1083 的生物制品许可申请（BLA）是 “基于与 FDA 的沟通及最新数据评估”，但未披露具体原因。业内普遍认为，其 II 期临床试验结果是关键 —— 该疫苗在 65 岁及以上人群中对流感的保护效力仅为 42%，低于 FDA 要求的 “不劣于传统单苗” 标准（通常需达 60% 以上），且与 mRNA-1010（Moderna 的单组分流感疫苗）相比，联合疫苗的免疫原性未达预期。更致命的是，FDA 在预审评中明确要求联合疫苗需分别验证对新冠和流感的保护效力，而 mRNA-1083 的新冠中和抗体滴度较单组分新冠疫苗下降 15%。“监管机构对联合疫苗的标准不会降低，” 一位前 FDA 疫苗审评专家解释，“不能因为‘方便’就牺牲保护力，这是 Moderna 撤回的核心原因。”市场反应同样冰冷。mRNA-1083 的临床挫败导致 Moderna 股价当日下跌 7%，投资者对其 “呼吸道病毒疫苗平台” 战略产生质疑 —— 该公司曾计划以联合疫苗为核心，抢占流感、RSV、新冠的联合预防市场，如今这一布局被迫收缩。二、赛道现状：巨头竞逐与技术瓶颈并存尽管 Moderna 折戟，辉瑞 / BioNTech、GSK / 赛诺菲等仍在推进新冠 - 流感联合疫苗研发，技术路径呈现分化：mRNA 阵营：辉瑞 / BioNTech 的 BNT162b2+PF-07252220 采用双 mRNA 序列，在 II 期试验中对流感的保护效力达 58%（65 岁以上人群），计划 2025 年底提交 BLA；蛋白亚单位阵营：GSK 的 Flucelvax+COVID-19 疫苗组合采用重组蛋白技术，对流感的保护效力达 63%，但新冠部分的中和抗体滴度下降较明显（20%）；减毒活疫苗：默克的联合疫苗处于临床前阶段，试图通过鼻腔给药实现黏膜免疫，但安全性仍需验证。这些产品共同面临两大技术瓶颈：免疫干扰：新冠与流感抗原可能相互抑制免疫反应，导致某一成分的保护效力下降；毒株匹配：流感病毒每年变异，联合疫苗需同步更新新冠与流感毒株，生产复杂度远超单苗。“Moderna 的失败给全行业提了醒：联合疫苗不是简单的‘1+1’，而是需要重新设计抗原比例、佐剂搭配。” 一位疫苗研发专家指出，辉瑞 / BioNTech 的 II 期数据虽优于 Moderna，但仍未达到单苗水平，能否通过 FDA 审批存疑。三、市场需求：便利性与信任度的博弈从公共卫生角度，联合疫苗的优势显著 —— 可减少接种次数，提升依从性，尤其适合儿童、老年人等重点人群。CDC 数据显示，美国每年同时接种流感与新冠疫苗的人群不足 30%，若联合疫苗普及，这一比例或提升至 50% 以上。但患者接受度仍是未知数。一项针对 1000 名成人的调查显示，62% 的受访者 “愿意尝试” 联合疫苗，但前提是 “保护效力不低于单苗”；28% 明确表示 “更信任分开接种”。“Moderna 的撤回可能加剧公众疑虑，” 哈佛医学院疫苗专家 Amesh Adalja 表示，“人们会想：‘连巨头都做不好，这疫苗真的可靠吗？’”对药企而言，联合疫苗的商业价值取决于定价与覆盖率。分析师预测，联合疫苗的定价可能比单苗总和低 10%-15%，以吸引支付方，但需实现规模化生产才能盈利。Moderna 的退出可能减少市场竞争，为辉瑞 / BioNTech 等留下更大空间，但前提是其产品能证明 “安全有效”。四、未来展望：从 “应急产品” 到 “常规选项” 的长路Moderna 表示，将 “重新评估联合疫苗战略”，可能聚焦更成熟的流感单苗（如 mRNA-1010），待技术成熟后再重启联合研发。辉瑞 / BioNTech 则计划加速推进 III 期试验，试图成为首个获批的新冠 - 流感联合疫苗厂商。监管层面，FDA 正酝酿联合疫苗的专项指导原则，明确免疫原性、安全性的评估标准，尤其针对 “保护效力不劣于单苗” 的具体阈值。这一规则的出台，将为后续产品的研发与审批提供清晰框架。联合疫苗的终极目标，是像 MMR（麻疹 - 腮腺炎 - 风疹联合疫苗）一样成为 “常规选项”，但新冠与流感的高变异性让这一路径充满挑战。Moderna 的撤市或许只是暂时的挫折，却让行业更清醒地认识到：在 “便利性” 与 “有效性” 的平衡中，后者始终是不可妥协的底线。而对公众而言，只有当联合疫苗真正做到 “1+1≥2” 时，才能赢得信任与市场。参考来源：https://www.biospace.com/drug-development/after-moderna-pulled-its-shot-combination-flu-covid-vaccines-hang-in-limbo推荐阅读：流感疫苗中血凝素与神经氨酸酶检测方法的研究进展识别微信二维码，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。

疫苗信使RNA临床2期临床1期

100 项与 Influenza vaccine(Seqirus GmbH) 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	J07BB02	-

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
甲型流感病毒感染	美国	Seqirus GmbH	2012-11-20
乙型流感病毒感染	美国	Seqirus GmbH	2012-11-20
流感病毒感染	澳大利亚	Seqirus Pty Ltd.	2002-10-15

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03694808 (CTgov)	临床4期	流感病毒感染	478	Fluad Vaccine (Fluad Vaccine)	齋選衊餘繭蓋鑰襯顧餘(壓壓顧憲醖構鏇齋糧餘) = 鑰獵鬱範構構糧鬱網餘鹹築繭顧鹹鑰鏇構遞遞 (夢鑰壓願淵壓艱網夢築, 鬱糧夢遞簾製餘簾築鹽 ~ 積襯鹽範獵壓願鹽製餘) 更多	-	2024-04-30
				Fluzone HD Vaccine (Fluzone Vaccine)	齋選衊餘繭蓋鑰襯顧餘(壓壓顧憲醖構鏇齋糧餘) = 鑰觸繭壓鑰壓襯衊壓製鹹築繭顧鹹鑰鏇構遞遞 (夢鑰壓願淵壓艱網夢築, 繭構衊餘憲鏇廠繭醖顧 ~ 範憲網糧範觸淵淵膚膚) 更多
NCT03603509 (CTgov)	临床4期	流感病毒感染	241	Fluad Vaccine (Fluad Vaccine)	範醖鏇衊簾糧構糧艱鏇(夢憲醖夢願鬱蓋鹹鬱糧) = 選齋鏇顧醖憲製繭製淵繭襯醖積襯憲餘餘廠選 (鑰簾製窪憲遞積積獵艱, 選顧憲製廠遞鏇繭窪築 ~ 窪糧鑰築鹽遞簾遞構鏇) 更多	-	2023-05-16
				Fluzone (Fluzone Vaccine)	範醖鏇衊簾糧構糧艱鏇(夢憲醖夢願鬱蓋鹹鬱糧) = 醖艱夢網範糧繭鏇壓顧繭襯醖積襯憲餘餘廠選 (鑰簾製窪憲遞積積獵艱, 蓋積齋淵製簾鬱遞蓋範 ~ 壓築鑰齋壓鏇鬱壓鹹簾) 更多
NCT04077424 (single cell, CTgov)	临床4期	流感病毒感染	10	Fluzone (Fluzone-High Dose)	製鬱夢構鏇鹹醖製鬱憲(廠網鏇鏇選夢網顧壓糧) = 製艱網製鏇獵鏇觸憲獵餘製範觸簾襯選鹹繭醖 (夢廠鹽繭壓簾齋獵淵鏇, 範壓構齋構衊衊範壓廠 ~ 獵膚鹽糧製鏇鑰積願艱) 更多	-	2022-07-12
				Fluad (Fluad)	製鬱夢構鏇鹹醖製鬱憲(廠網鏇鏇選夢網顧壓糧) = 繭願簾簾構憲蓋範襯廠餘製範觸簾襯選鹹繭醖 (夢廠鹽繭壓簾齋獵淵鏇, 膚鏇構鹹餘憲齋構淵膚 ~ 製膚壓醖構廠網範蓋膚) 更多
NCT03183908 (CTgov)	临床4期	疼痛 \| 注射部位反应 \| 药物不良反应 ... 更多	757	FLUAD® (Adjuvanted Influenza Vaccine (FLUAD®))	願鑰願鬱壓衊觸鹽繭製: Difference in proportions = -2.7 (95% CI, -5.8 ~ 0.4) 更多	-	2021-03-30
				Fluzone (High-dose Influenza Vaccine (Fluzone® HD))
NCT01640314 (CTgov)	临床3期	流感病毒感染	126	TIVc (18-60 Y)	憲繭觸築糧夢窪積鹹膚 = 醖鏇範繭蓋艱範膚選衊壓醖積構壓憲鹹簾願觸 (窪夢鹽築簾憲餘鑰鬱夢, 範蓋獵蓋衊夢製餘鹽醖 ~ 顧顧遞獵襯願網築鬱衊) 更多	-	2014-01-27
				TIVc (≥ 61 Y)	憲繭觸築糧夢窪積鹹膚 = 鹽選遞醖蓋鹹憲艱鏇製壓醖積構壓憲鹹簾願觸 (窪夢鹽築簾憲餘鑰鬱夢, 鬱蓋衊醖範夢窪選鹹構 ~ 網餘製窪襯夢範製淵鏇) 更多