Immunogenicity and Safety of Quadrivalent Recombinant Influenza Vaccine Compared With Egg-Based Standard-Dose Quadrivalent Influenza Vaccine in Children 3 to 8 Years of Age.

The purpose of this study was to demonstrate the non-inferior HAI immune response of quadrivalent recombinant influenza vaccine (RIV4) vs licensed Egg-Based Quadrivalent Influenza Vaccine (IIV4) for the 4 strains based on the egg-derived antigen in all participants aged 3 to 8 years and to describe the immunogenicity and safety profile of RIV4 compared to IIV4 in participants aged 3 to 8 years.

开始日期2022-11-10

申办/合作机构

Sanofi Pasteur SA

NCT05409612

/ Completed临床3期IIT

Multicenter, Randomized, Open, Phase III, Trial Assessing the Immunogenicity and Safety of Two Influenza Vaccine Strategies Among Severe Obese Adult Patients

Obesity has been considered as a risk factor for mortality and development of complications during infection with the influenza virus. Several case studies of severe and fatal infections have identified possible effects of obesity on disease progression; these effects include extensive viral replication in the deep lung, progression to viral pneumonia, and prolonged and increased viral shedding. These points may be linked to obesity which causes a chronic state of meta-inflammation with systemic implications for immunity: obese patients exhibit delayed and blunted innate and adaptive immune responses to influenza virus infection, and they experience poor recovery from the disease leading to an increased susceptibility to secondary bacterial infections and poor healing of the lung epithelium. Furthermore, in obese people, influenza virus may exploit the lack of antiviral pressure, generate a more virulent population and increase disease severity Due to the growing prevalence of obesity worldwide (500 million subjects in 2017), it is important to be able to offer vaccines that provide the highest protection for this at-risk population. The quadrivalent recombinant high-dose influenza vaccine has been shown to have greater immunogenicity and efficacy than standard influenza vaccine in non-obese adults older than 50 years. However, this vaccine has never been evaluated in obese subjects.
Investigators thus planned this trial to assess whether the use of the new quadrivalent recombinant high-dose influenza vaccine (RIV4) will induce a better immunological answer than current quadrivalent standard vaccine (SD) in patients with severe obesity, with an acceptable safety profile, thus leading to a better protection against influenza in this population at high risk of influenza complications.

开始日期2022-11-07

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

[+2]

NCT05513053

/ Completed临床3期

Immunogenicity and Safety of Quadrivalent Recombinant Influenza Vaccine (RIV4) in Children and Adolescents Aged 9 to 17 Years and Adults Aged 18 to 49 Years.

The purpose of this study was to demonstrate the non-inferiority (NI) of the HAI immune response of RIV4 in participants aged 9 to 17 years vs participants aged 18 to 49 years and to describe the immunogenicity and safety profile of RIV4 in all participants.

开始日期2022-10-27

申办/合作机构

Sanofi Pasteur SA

100 项与重组四价流感疫苗(Protein Sciences) 相关的临床结果

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项与重组四价流感疫苗(Protein Sciences) 相关的文献（医药）

2025-05-01·LANCET INFECTIOUS DISEASES

Comparative assessment of immunogenicity and safety of recombinant influenza vaccine in children, adolescents, and adults: results from a phase 3, immunobridging, open-label, non-randomised study

Article

作者: See, Stephanie ; De Bruijn, Iris ; Kaas-Leach, Kathleen ; Tabar, Cynthia ; Pepin, Stephanie ; Konieczny, Marek ; Folegatti, Pedro M ; Drazan, Daniel ; Essink, Brandon ; Natalini Martínez, Silvina ; Bertoch, Todd ; Talanova, Oxana ; Fries, Katherine

BACKGROUND:

The recombinant influenza vaccine (RIV) is licensed for adults older than 18 years but is not approved for paediatric groups. This study aimed to demonstrate the non-inferior immune responses and safety of RIV in participants aged 9-17 years compared with adults aged 18-49 years.

METHODS:

This was a phase 3, non-randomised, immunobridging, open-label, uncontrolled study conducted at 36 centres in Europe and the USA during the 2022-23 northern hemisphere influenza season. The main exclusion criteria were receipt of an influenza vaccine up to 6 months before enrolment and receipt of any other vaccines within 4 weeks before or after study intervention (except for COVID-19 vaccination, which was allowed at least 2 weeks before or after enrolment). Healthy participants aged 9-49 years received a single dose of quadrivalent RIV and were followed up for 6 months on days 9, 29, and 181. Haemagglutination inhibition (HAI) assays to assess immunogenicity were used to test blood samples obtained at baseline and day 29. The primary outcome was the non-inferiority of immune response at day 29 as assessed by HAI titre ratios and differences in seroconversion rates between the two age groups. The non-inferiority of a geometric mean titre was demonstrated if the lower limit of the two-sided 95% CI of the geometric mean titre (GMT) ratio was above 0·667 for each of the four strains of virus. Similarly, the non-inferiority of seroconversion was demonstrated if the lower limit of the two-sided 95% CI was -10% or above for each of four strains. Safety was monitored throughout the study. This study was registered at ClinicalTrials.gov (NCT05513053) and is complete.

FINDINGS:

Between Oct 27, 2022, and May 1, 2023, a total of 1308 participants were enrolled, all of whom attended the first study visit. 1299 participants (99%) received the study vaccine (641 participants [49%] in the age 9-17 years group and 658 participants [51%] in the age 18-49 years group). The mean age of participants in the age 9-17 years group was 13·0 years (SD 2·5) and was 34·3 years (9·2) in the age 18-49 years group. Overall, 707 participants (54%) were female and 601 participants (46%) were male. Most of the participants were White (1003 [77%] of 1308); the next largest category was Black or African American (255 [19%]); 149 (11%) participants identified as Hispanic or Latino. The HAI GMT ratio between the paediatric and adult groups at day 29 in the per-protocol analysis set was 2·0 (95% CI 1·7 to 2·3), 3·3 (2·8 to 3·9), 1·6 (1·4 to 1·8), and 1·2 (1·1 to 1·4) for A/H1N1, H3N2, B/Victoria, and B/Yamagata, respectively. Differences in seroconversion between the groups were 1·9 (-2·8 to 6·6), -0·6 (-4·4 to 3·2), 3·3 (-1·6 to 8·1), and 14·3 (9·2 to 19·3) for each of the four strains, respectively. The safety profile was comparable in both age groups, except for solicited reactions within 7 days post-vaccination that were fewer in children and adolescents (274 [44%] of 618; 95% CI 40 to 48) than in adults (336 [53%] of 635; 49 to 57). No related serious adverse events, deaths, or adverse events of special interest were reported.

INTERPRETATION:

RIV4 induced non-inferior immune responses in the participants aged 9-17 years compared with those aged 18-49 years. No safety concerns were reported.

FUNDING:

Sanofi.

2025-04-01·VACCINE

A phase I study of the safety, reactogenicity and immunogenicity of two quadrivalent seasonal influenza vaccines (Fluzone® or Flublok®) with or without one of two adjuvants (AF03 or Advax-CpG55.2) in healthy adults 18–45 years of age

Article

作者: Frey, Sharon E ; Bryant, Christopher ; Creech, C Buddy ; Abate, Getahun ; Alefantis, Timothy ; Anderson, Evan J ; Tuyishimire, Bonifride ; Rouphael, Nadine ; Makhene, Mamodikoe ; Campbell, James ; Pandey, Aseem ; Rostad, Christina A ; Sridhar, Saranya ; Walter, Emmanuel B ; Petrovsky, Nikolai ; Honda-Okubo, Yoshikazu ; Winokur, Patricia ; Smith, Michael J ; Hegmann, Theresa E ; Goncalvez, Ana P ; El Sahly, Hana M ; Whitaker, Jennifer A ; Paulsen, Grant ; Roberts, Paul C ; Ustyugova, Irina V

Seasonal influenza continues to cause significant morbidity and mortality, particularly for the elderly and immunocompromised. Current licensed influenza vaccines provide only partial protection even for immunocompetent hosts. Vaccine adjuvants can improve the magnitude and breadth of immune responses and there is considerable interest in identifying new adjuvants that can improve immune responses to seasonal influenza vaccines. This phase I, randomized, double-blind trial evaluated the safety and immunogenicity of one dose of 2018/2019 quadrivalent influenza vaccine (either Fluzone® or Flublok®) administered intramuscularly with or without one of two adjuvants (AF03 or Advax-CpG55.2). A total of 241 healthy adults aged 18-45 years were enrolled and randomized to 1 of 6 groups. Groups 1-3 received one dose of Fluzone® QIV 2018/2019 administered alone or with AF03 or Advax-CpG55.2 and Groups 4-6 received one dose of Flublok® QIV 2018/2019 alone or with one of these two adjuvants. All participants received Fluzone® or Flublok® QIV 2019/2020 ninety days later. Primary objectives were to evaluate safety and reactogenicity along with changes in hemagglutinin inhibition (HAI), neuraminidase inhibition (NAI) and neutralizing antibodies to 2018/2019 seasonal influenza antigens, comparing Day 1 and Day 29 titers. Secondary objectives evaluated the impact of adjuvants on immune responses after subsequent doses of unadjuvanted seasonal influenza vaccine and immunologic responses to heterologous influenza H1 and H3 antigens. Overall, the adjuvanted vaccines were safe and generated robust immune responses against both homologous and heterologous strains. Similar responses were seen across all six study arms. Both adjuvants were associated with qualitatively improved immune responses against some strains at varying timepoints, but results were inconsistent. There were no substantial differences in safety or reactogenicity identified between the study groups and all vaccine formulations were well tolerated. In this highly immunologically-experienced cohort, neither AF03 nor Advax-CpG55.2 demonstrated notable benefit when added to the seasonal influenza vaccine. (ClinicalTrials.gov ID# NCT03945825).

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 ; Thompson, Mark G ; Kain, Jessica ; 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 ; Lee, Justin S ; Stevens, James ; 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 ; Georgiou, George ; Pohl, Jan ; 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.

项与重组四价流感疫苗(Protein Sciences) 相关的新闻（医药）

2025-05-14

·生物制品圈

SP0273 & SP0237——Sanofi流感疫苗管线

导读：疫苗接种是防控传染病的关键手段，尤其对于控制新兴病原体的大流行至关重要。近年来，mRNA疫苗技术的突破为传统疫苗技术带来了更安全的选择。新冠肺炎疫苗的临床效果已经显现，同时，众多候选疫苗也在积极推进临床开发。Sanofi在mRNA流感疫苗的研发与生产领域持续倾注了大量精力与资源。2024年7月25日，Sanofi发布的第二季度财报中，流感疫苗作为公司的优势品种，二季度销售额达到了1.15亿欧元。在此次财报公布的同时，Sanofi也做出了一项重要决策调整：决定将目前处于I期临床阶段的mRNA流感疫苗SP0273从其研发管线中移除，转向推进另一款更具潜力的mRNA流感疫苗SP0237进入I期临床阶段。图1 Sanofi SP0237研发管线01mRNA流感疫苗SPO273 临床进展2022年6月9日，Sanofi开启了对SP0273的I期临床试验（NCT05426174）[1]，这是一项首次人体试验、随机、改良双盲、活性对照、剂量递增研究，旨在评估多达3个剂量水平的mRNA NA疫苗的安全性和免疫原性，疫苗以单次肌肉注射的方式注射给18岁及以上的健康成年人。此研究研究将包括两个年龄组，即18至64岁和≥65岁。此研究将包括一次筛选访问、在第1、3、9、29、91和181天进行的6次研究访问以及在第366天进行的安全随访电话。该试验共招募233名志愿者，于2024年1月3日完成试验。在2023年6月举办的Sanofi投资者活动上，公司公布了SP0273疫苗的最新试验结果。据研究结果显示，SP0273在针对甲型流感病毒的免疫原性方面展现出了较强的性能，然而，在应对B型流感病毒时则相对较弱。尽管在反应原性方面，SP0273的表现仍不及重组疫苗和灭活疫苗；但在全身反应方面，SP0273优于Moderna的流感mRNA疫苗（图2）[2]。这一综合评估不仅为Sanofi提供了宝贵的研发反馈，也为后续疫苗策略的调整与优化指明了方向。图2 SP0273的临床试验结果此外，在同一活动上，Sanofi还透露了一项令人振奋的研发进展，公司正借助机器学习的力量，致力于新一代流感mRNA疫苗的研发。这一策略通过运用先进的计算技术，对菌株选择进行了精细优化，以期在疫苗研发过程中实现更高的效率和精确度。值得一提的是，Sanofi在疫苗抗原组成上进行了深入探索，重点研究加入神经氨酸酶（NA, Neuraminidase），旨在显著提升疫苗的有效性。会上，Sanofi还公布了关于mRNA Neuraminidase的试验结果，数据表明其免疫原性与市场上广受认可的Fluzone HD疫苗可相媲美，同时在耐受性和安全性方面也展现出了良好的表现（图3）。这一成果不仅验证了Sanofi在流感mRNA疫苗研发领域的创新能力，也为未来疫苗产品的进一步优化与升级奠定了坚实基础。图3 mRNA Neuraminidase的临床试验结果02新一代流感疫苗SPO273 临床进展Sanofi在发布其2024年第二季度财报时宣布了一项重要决定，公司决定终止四价流感mRNA疫苗SP0273的临床I期试验。不过，这一变动并未减缓Sanofi在流感mRNA疫苗研发领域的步伐。基于SP0273及mRNA Neuraminidase的研究成果，Sanofi正积极推进另一款流感mRNA疫苗——SP0237进入I期临床试验阶段[3]。SP0237作为新一代流感mRNA疫苗，在设计上进行了创新，包含了血凝素（HA, Hemagglutinin）和神经氨酸酶（NA, Neuraminidase）两种抗原，旨在进一步提升疫苗的保护效率，确保更加全面有效的防护。2024年4月1日，Sanofi开启了对SP0237的I/Ⅱ期临床试验（NCT06361875）[4]，此次试验的目的是评估单次肌肉注射三种不同配方的四价mRNA流感疫苗SP0237与活性对照（QIV-标准剂量（SD）、QIV-高剂量（HD）（≥65岁的成年人）或四价重组流感疫苗（RIV4）在18岁及以上的成年人中的安全性和免疫原性。每位参与者的研究持续时间约为12个月，注射7种QIV mRNA中的一种或对照剂中的一种，剂量递增并按顺序入组。试验预估在2025年5月份完成。03结语Sanofi在mRNA流感疫苗领域的持续探索，为我们展示了疫苗技术的未来发展方向。从SP0273到SP0237，每一次的尝试与调整，都旨在为我们带来更安全、更有效的疫苗选择。SP0237作为新一代流感mRNA疫苗，不仅继承了前代疫苗的优点，更在抗原组成上进行了优化，以期提高疫苗的保护率。Sanofi的持续创新和对疫苗质量的严格要求，为全球流感防控贡献了重要力量，也让我们对SP0237的未来充满期待。参考文献 [1]https://clinicaltrials.gov'study/NCT0542617412]https:/'vww,sanoficom/en/investors/financial-results-and-events/investorpresentations/vaccines-investor-event[3]https://wwwsanofi.com/en/investors/financial-results-and-events/financial-results/q2resu1ts-2024[4]https:/clinicaltrials.gov'study/NCT06361875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。

财报疫苗信使RNA临床1期

2024-11-15

·生物制品圈

挥别1.0迎接2.0时代？中国流感疫苗市场既要破局也要进阶

目前中国已获批上市的流感疫苗至少有十余款，在接种率瓶颈下，除了鼻喷流感疫苗和亚单位流感疫苗外，其余流感疫苗在工艺、保护效果上的同质化严重（内卷），即呈现无细胞生产、无创新佐剂、无重组工艺、无高剂量的特点，指南也没有针对人群的优先使用推荐。目前企业对流感疫苗的研发可能存在两种分歧：价格战下继续开发雷同疫苗可能卷不动了，开发其他创新疫苗的思路在何方？对于一款全球服役了数十年的疫苗来说，流感疫苗在中国还很年轻，远远未到“躺平”的时候。改进流感疫苗效果可能会有助于打破现有的价格战僵局，尤其是在后疫情时代公众对疫苗有效性期望更高的情况下，并有望加快实现流感疫苗的市场分层。近日Vaccine发表了一项关于未来几年流感疫苗研发方向或思路的综述，为我国流感企业走出内卷可提供思路借鉴。内容摘选如下：当前流感疫苗市场现状目前可用的流感疫苗的年有效性通常在<20%-60%之间，疫苗类型、剂量和佐剂的加入会影响疫苗在不同目标人群中的效果。如果疫苗株与流行毒株没有表现出高度的抗原相似性，那么在推荐疫苗株后（北半球季节为 2 月，南半球季节为 9 月）出现季节性流感病毒“漂移”也可能降低疫苗有效性。在既定的流感流行季，有效性通常因流感病毒亚型/谱系而异，尤其是H3N2亚型，它在疫苗病毒中往往表现最差，甚至在单个季节内H3N2病毒的不同系统发育亚群或变体之间可能存在有效性差异。此外，人群中不同的免疫力和/或既往通过疫苗接种或自然感染暴露于流感病毒，可能会影响流感疫苗的有效性。全球季节性流感疫苗市场很稳定，2022 年各国采购了约7.6 亿剂，中低收入国家使用受限，主要由中高收入国家使用。目前的流感疫苗制造商不一定受到市场的激励来增加现有疫苗的产量，比如2019 年季节性流感疫苗的最大年生产能力为15 亿剂，但同年全球分发约5.31亿剂流感疫苗就侧面说明了这一问题。据估计，2024 年全球需求量为 8.5 亿剂。由明尼苏达大学传染病研究与政策中心（CIDRAP）领导的流感疫苗研发路线图（IVR），该路线图是29个国家的100 多个利益相关者合作的结果，开发了通用流感疫苗技术布局。左侧蓝色象限为增强型季节性流感疫苗路线，右侧紫色象限为下一代流感疫苗技术路线。什么是增强型季节性流感疫苗？旨在改进传统标准剂量流感疫苗的任何流感疫苗，包括持久性、功效、保护范围或规划适用性，增强型季节性流感疫苗和下一代流感疫苗都被认为是改进的流感疫苗。增强型季节性流感疫苗：基于目前获得许可的传统流感疫苗（即针对来自流行的季节性流感病毒的HA的基于鸡蛋和细胞的灭活疫苗和LAIV 疫苗）的技术和方法的任何流感疫苗商品，该类疫苗商品通过佐剂、剂量或制造工艺（即重组技术）进行了增强，以提供比传统标准剂量季节性流感疫苗更高的免疫原性、疗效和/或有效性。佐剂在内的佐剂灭活流感疫苗：主要是CSL公司生产的MF59佐剂的流感疫苗；高剂量灭活流感疫苗（与标准剂量疫苗相比，每种毒株的HA含量更高）：主要是Sanofi生产的高剂量剂型的Fluzone。重组季节性流感疫苗：重组HA蛋白流感疫苗（RIV，例如Sanofi的Flublok、Supemtek，昆虫细胞干状病毒表达）、病毒样颗粒疫苗（Cadiflu-S，仅印度）。 HA = 血凝素;IIV = 灭活流感病毒;LAIV = 流感病毒减毒活疫苗;N/A = 不适用;SAGE = 战略咨询专家组。目前证据显示，高剂量和佐剂IIV可为65岁以上的成人提供更好的保护，其次是基于细胞的IIV和RIV。什么能称为下一代流感疫苗？下一代流感疫苗，是指在设计中使用与当前许可疫苗不同的方法或技术的任何疫苗商品，主要目标是引发更好的免疫反应，或者比目前获得许可的流感疫苗更有效，或者至少表现出不劣于目前许可的流感疫苗。包括：通用流感疫苗：对甲型和乙型流感病毒的任何流感毒株具有保护作用，与亚型、变化或漂移无关。广谱保护的流感疫苗：对多种流感病毒具有保护作用，但不符合通用疫苗的标准：亚型特异性（例如，仅 H1 型）、单个组中的多个子类型、泛组（所有 1 组或 2 组甲型流感）、所有乙型流感病毒。下一代季节性流感疫苗：疫苗包含基于 WHO 推荐菌株的配方和/或专为季节性保护而设计的疫苗，比目前批准的季节性流感疫苗提供更好（更持久或更有效）的季节性流感疫苗，使用较多工艺为基于mRNA平台的流感疫苗。 Moderna的mRNA-1010的最新3期试验结果表明，与获得许可的标准剂量疫苗对照相比，甲型和乙型毒株的GMT和血清转化率更高。与增强型季节性流感疫苗（Fluzone High-Dose）相比，mRNA-1010还在老年人中诱导更高（甲型流感毒株和 B/Victoria）或类似（B/Yamagata）的HAI滴度。辉瑞的3期四价mRNA 候选疫苗与获批流感疫苗相比表现出非劣效性，针对甲型流感表现出更好的免疫原性终点。与其他呼吸道疾病联合的流感疫苗：包含流感成分和另一种呼吸道病原体的疫苗，Novavax、Moderna 和 Pfizer 正在开发SARS-Cov-2/流感联合候选疫苗，且均处于III期阶段。此外辉瑞和Moderna 都在开发SARS-CoV-2/流感和RSV/流感mRNA联合疫苗，目前三种组合产品正处于3期试验中。数据显示，辉瑞的SARS-CoV-2和流感候选疫苗联合疫苗在所有疫苗匹配毒株中，相对于已获批的四价流感疫苗，其HAI GMT比值均大于1。对于所有四种流感疫苗株，相对于获得许可的四价流感疫苗，Moderna的mRNA-1083 在 50-79 岁成人中的HAI GMT比率同样大于1。（A）每个疫苗平台在临床开发中所有下一代流感候选疫苗中的份额（B）按疫苗平台划分的通用或广泛保护性、下一代季节性和联合流感疫苗的候选疫苗数量（C）正在或已经完成I/II/III期临床试验的候选疫苗数量。下一代进入临床试验的候选季节性流感疫苗几乎是正在开发的通用或广泛保护产品的两倍，技术路线主要集中在mRNA领域。三种下一代季节性产品正处于 3 期临床试验中，特别是辉瑞的四价流感modRNA 疫苗、Moderna的 mRNA-1010以及Novavax和Emergent BioSolutions的NanoFlu。资料来源：Taaffe J, Ostrowsky JT, Mott J, et al. Advancing influenza vaccines: A review of next-generation candidates and their potential for global health impact. Vaccine. 2024 Oct 5;42(26):126408. doi: 10.1016/j.vaccine.2024.126408. 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点，不代表本站立场。

疫苗带量采购

2024-09-14

·生物制品圈

流感疫苗未来10年的市场预期、疫苗应用效果及发展趋势

与WHO今年预测的未来几年全球流感疫苗市场需求量趋于稳定不同，9月13日美国医疗行业市场评估机构针对流感疫苗产值发布了一项行业报告，报告称：全球流感疫苗市场预计将从2023年的67亿美元增长到2033年的139亿美元，2024年2033年的复合年增长率为7.6%。疫苗成分的不断更新和疫苗接种建议的扩大推动了这一增长。例如，2024-2025 年流感疫苗已更新，以增强其对当前病毒株的效力。此外，CDC 等卫生当局现在建议6个月以上的每个人每年接种疫苗，旨在增强人群免疫力并遏制流感的传播。高剂量和佐剂疫苗越来越多地被提倡用于老年人等高危人群，以激发更强的免疫反应。此外，市场看到疫苗类型多样化，包括重组和基于细胞培养的疫苗，以适应不同的健康状况和偏好。该策略旨在提高不同人口群体的疫苗接种率，同时加强公共卫生运动有助于缓解疫苗犹豫并更有效地宣传流感疫苗接种的好处。技术进步也在重塑疫苗管理：正在研究皮内系统和微针贴片等创新，以简化和增强疫苗接种过程，从而有可能提高公众依从性。这些改进对于扩大疫苗的覆盖范围和有效性至关重要，尤其是在应对年度流感季节和新出现的流感挑战方面。最近的事态发展凸显了实现更广泛、更具包容性的保护的重大推动。2024年1月，Novavax开始对其通用流感候选疫苗 NVX-102 进行3期试验，该疫苗针对普遍保守的病毒区域，可能针对更广泛的毒株提供保护。此外，2023年12月，阿斯利康和 Seqirus 合作开发下一代流感疫苗，重点是广谱保护。其他值得注意的进展包括欧盟于2023年10月批准赛诺菲巴斯德的四价FLUONE高剂量流感疫苗用于老年人，以加强对老年人流感并发症的保护。GSK还将其mRNA季节性流感候选疫苗推进到III期试验，突显了mRNA 技术在疫苗开发中的广泛使用。这些举措表明该行业坚定地致力于提高流感疫苗接种的有效性和包容性，并推动这一重要医疗保健领域的持续创新。报告关键要点市场增长：流感疫苗市场预计将从 2023 年的 67 亿美元增长到 2033 年的 139 亿美元，复合年增长率为 7.6%。灭活疫苗：以92.9%的份额主导市场，由于广泛的偏好和可靠性，其表现优于其他类型。四价疫苗：以58.2%的收入份额引领市场，因其全面的保护和成本效益而受到青睐。目标人群：成年人占市场的78.4%，主要是由于有针对性的免疫接种活动和人口老龄化。给药方法：注射是首选方法，占据 60.7% 的市场份额，鼻喷雾剂因其便利性而受到青睐。一级分销商：医院和零售药店以37.4%的份额引领分销，这得益于流感病例频繁导致疫苗接种率高。区域主导地位：北美占据最大的市场份额，为 53.9%，欧洲紧随其后。亚太地区增长：在政府的大力支持和公共卫生意识的提高下，预计市场将快速增长。行业发展：最近的活动包括疫苗批准和领先制药公司之间的战略合作伙伴关系。流感疫苗统计数据疫苗分发和有效性： 2022-2023年流感季，美国分发了1.734亿剂流感疫苗。该疫苗在2022-2023流感季的有效性估计为54%，这是自 2013 年以来的最高有效性。疫苗接种率： 2022-2023流感季，大约46.9% 的美国成年人接种了流感疫苗，比上一季的49.4%下降了2.5%。对于 6 月龄至17岁的儿童，疫苗接种率稳定在57.4%，与 2021-22流感季的57.8%相似。具体而言，6月龄至4岁儿童的流感疫苗接种覆盖率为65.6%，5-12 岁儿童为59.3%，13-17 岁青少年为 49.0%，均与上一季节持平。 2022-23流感季的整体疫苗接种率比大流行前的2019-2020流感季低6.3%，后者为63.7%。流感疫苗接种的影响： 2019-2020年流感季节，流感疫苗接种预防了大约 700 万例流感疾病、300 万次与流感相关的就诊、100,000 例住院治疗和 7,000 例与流感相关的死亡。 2021年的一项研究强调，与未接种疫苗的人相比，因流感住院的接种疫苗的成年人入住 ICU 的几率降低了26%，死亡风险降低了31%。根据2018年的一项研究，接种疫苗的成年人因流感而入住 ICU 的可能性要低59%，如果入院，他们平均比未接种疫苗的患者少住院 4 天。 2020 年的一项研究表明，在 2018-2019 年流感季节，流感疫苗接种使 6 个月至 17 岁儿童的住院率降低了 41%，急诊就诊率减少了一半。 2022 年的研究表明，流感疫苗接种可将儿童患严重、危及生命的流感的风险降低 75%。新兴趋势基于 mRNA 的疫苗：利用 COVID-19 mRNA 疫苗的成功，mRNA 技术现在正在应用于流感疫苗。这种方法允许快速灵活的生产，从而有可能增强疫苗株和传播病毒之间的匹配。美国卫生与公众服务部在这项技术上投入了大量资金，其中 Moderna 引领了进步，这一趋势凸显了 mRNA 疫苗在改善流感疫情应对和大流行防范方面的潜力。病毒样颗粒（VLP）疫苗：VLP 疫苗处于流感预防策略的最前沿。它们模仿病毒的结构，但缺乏遗传物质，这意味着它们不会引起感染。这种类型的疫苗会刺激 T 细胞和 B 细胞免疫反应，从而为更广泛地预防流感提供保护。其灵活的配方能力使 VLP 疫苗成为流感预防不断发展的有前途的选择。重组血凝素（HA）疫苗：赛诺菲巴斯德的 Flublok 是重组 HA 疫苗的一个例子，它利用尖端技术比传统方法更快地生产血凝素蛋白。这种方法不仅可以加快疫苗生产速度，还可以最大限度地降低基于鸡蛋的生产过程中可能发生的突变风险。重组 HA 疫苗对于快速应对大流行威胁尤为重要。佐剂和高剂量疫苗：人们对佐剂和高剂量流感疫苗的兴趣日益浓厚，特别是对于老年人或免疫系统受损等弱势群体。这些疫苗，包括 HD-IIV3 和 aIIV3 等制剂，旨在引发更强的免疫反应，这对于有效保护这些高危人群至关重要。内容来源：media.market.u，作者Trishita Deb（笔者译）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点，不代表本站立场。

疫苗信使RNA临床3期

100 项与重组四价流感疫苗(Protein Sciences) 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	J07BB	-

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
流感病毒感染	欧盟	Sanofi Winthrop Industrie SA	2020-11-16
流感病毒感染	冰岛	Sanofi Winthrop Industrie SA	2020-11-16
流感病毒感染	列支敦士登	Sanofi Winthrop Industrie SA	2020-11-16
流感病毒感染	挪威	Sanofi Winthrop Industrie SA	2020-11-16

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
接种疫苗	临床3期	美国	Sanofi Pasteur SA	2022-10-27
接种疫苗	临床3期	捷克	Sanofi Pasteur SA	2022-10-27
接种疫苗	临床3期	波兰	Sanofi Pasteur SA	2022-10-27
接种疫苗	临床3期	西班牙	Sanofi Pasteur SA	2022-10-27

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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


NCT05514002 (Pubmed \| Open Forum Infect Dis)	临床4期	流感病毒感染	3,988	Recombinant Influenza Vaccine (RIV)	蓋夢鹽壓憲膚鑰蓋獵糧(窪繭鹹顧觸鏇鑰顧餘襯) = 願醖憲蓋鬱艱繭餘蓋醖觸鏇繭蓋憲觸鏇鬱獵願 (糧鑰襯積鹹窪夢膚膚繭 )	积极	2024-09-27
				Standard-Dose Inactivated Influenza Vaccine (SD IIV)	蓋夢鹽壓憲膚鑰蓋獵糧(窪繭鹹顧觸鏇鑰顧餘襯) = 艱製鏇艱製淵鬱鹹獵窪觸鏇繭蓋憲觸鏇鬱獵願 (糧鑰襯積鹹窪夢膚膚繭 )
NCT05513391 (CTgov)	临床3期	接种疫苗 \| 流感病毒感染	366	RIV4 (RIV4)	鹹鹽鑰淵鏇衊鏇繭鏇鑰(鬱鬱醖糧願憲蓋鬱觸觸) = 選鹹壓淵餘餘簾範顧憲壓鬱範鏇鏇鹹鏇積淵觸 (築顧衊觸構積壓顧網齋, 齋顧廠獵構夢範餘鏇願 ~ 憲積襯繭鏇範齋鏇遞餘) 更多	-	2024-07-24
				IIV4 (IIV4)	鹹鹽鑰淵鏇衊鏇繭鏇鑰(鬱鬱醖糧願憲蓋鬱觸觸) = 範憲網糧壓廠壓窪艱觸壓鬱範鏇鏇鹹鏇積淵觸 (築顧衊觸構積壓顧網齋, 選窪壓壓積淵艱窪窪夢 ~ 壓鬱膚糧製網顧製夢艱) 更多
NCT03722589 (CTgov)	临床4期	流感病毒感染	944	Flublok (Flublok (Recombinant))	鹽構鹽齋糧願蓋鑰遞願 = 遞鏇獵糧糧齋窪觸鏇壓淵觸遞遞積衊齋觸齋衊 (獵醖範壓鏇觸鏇鏇糧鏇, 選鬱獵網蓋淵積築蓋繭 ~ 鬱鏇齋範齋蓋願製襯鏇) 更多	-	2024-07-22
				Flucelvax (Flucelvax (Cell-based))	鹽構鹽齋糧願蓋鑰遞願 = 艱願繭範壓鹹壓鹹壓鏇淵觸遞遞積衊齋觸齋衊 (獵醖範壓鏇觸鏇鏇糧鏇, 憲鏇願鬱襯願鏇淵糧齋 ~ 鹹糧製觸齋範鏇獵艱鏇) 更多
NCT04523324 (CTgov)	临床4期	甲型流感病毒感染 \| 流感病毒感染	577	Flublok™ Quadrivalent by Sanofi, Inc. (RIV4 (Flublok Quadrivalent))	簾範顧齋築壓範構獵糧(壓願衊鏇繭襯製觸構壓) = 餘獵餘繭糧壓窪蓋獵鏇淵醖網觸築襯遞夢簾顧 (醖製鏇夢鬱繭鏇廠膚衊, 製艱顧網鬱繭鏇遞壓築 ~ 構蓋鹹淵鑰製鹹窪膚範) 更多	-	2023-11-15
				VaxigripTetra™ by Sanofi, Inc. (IIV4 (Vaxigrip Quadrivalent))	簾範顧齋築壓範構獵糧(壓願衊鏇繭襯製觸構壓) = 製夢構鬱構簾壓積簾觸淵醖網觸築襯遞夢簾顧 (醖製鏇夢鬱繭鏇廠膚衊, 鬱顧製選艱願願壓蓋築 ~ 壓繭醖積襯範遞淵醖齋) 更多
NCT05144945 (CTgov)	临床3期	流感病毒感染	301	Quadrivalent Recombinant Influenza Vaccine (RIV4) (Group 1: Quadrivalent Recombinant Influenza Vaccine (RIV4))	齋願顧鬱範糧構鏇壓壓(膚構鹹遞壓鏇製膚製網) = 廠淵鬱選廠願積願構糧觸齋衊餘膚憲糧醖積網 (餘顧餘夢鹹艱壓膚鹽觸, 艱製製網壓遞廠憲範積 ~ 選醖壓範蓋夢鬱構壓齋) 更多	-	2023-09-29
				Quadrivalent inactivated influenza vaccine (Group 2: Quadrivalent-inactivated Influenza Vaccine (IIV4))	齋願顧鬱範糧構鏇壓壓(膚構鹹遞壓鏇製膚製網) = 願觸鏇蓋鹹壓醖願構遞觸齋衊餘膚憲糧醖積網 (餘顧餘夢鹹艱壓膚鹽觸, 鑰醖淵餘範膚鹽糧選遞 ~ 憲觸製夢衊窪積簾觸築) 更多
NCT03658629 (CTgov)	临床2期	流感病毒感染	1,375	Placebo+Quad-NIV-1+NanoFlu (Quad-NIV) (Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A)	憲窪衊窪壓範構淵艱願 = 夢鏇選衊築齋顧衊壓淵鏇遞顧蓋襯製鏇鑰廠壓 (憲獵獵遞鬱醖鑰醖艱糧, 獵獵鹽廠觸範鏇遞艱網 ~ 醖窪艱鏇顧膚鏇蓋糧範) 更多	-	2022-11-04
				Quad-NIV (Quad-NIV Preformulated With Adjuvant Dose A)	憲窪衊窪壓範構淵艱願 = 糧壓襯壓獵夢醖遞顧廠鏇遞顧蓋襯製鏇鑰廠壓 (憲獵獵遞鬱醖鑰醖艱糧, 鹽簾窪鏇艱鬱積積願淵 ~ 積齋鹽糧齋積範積襯餘) 更多
NCT03617523 (GRC90, CTgov)	临床4期	流感病毒感染	240	Fluzone Quadrivalent vaccine (Fluzone Quadrivalent Vaccine Group 1: 6 to <36 Months)	衊憲顧襯夢醖夢築範齋 = 壓壓繭襯鬱鑰鹹鹹襯壓壓鹽壓構壓鑰範願憲艱 (遞構製願願製壓衊築簾, 鏇構遞餘積築艱鹹壓選 ~ 鑰遞製齋繭糧鬱顧鑰鏇) 更多	-	2019-11-25
				Fluzone Quadrivalent vaccine (Fluzone Quadrivalent Vaccine Group 2: 3 to <9 Years)	鑰簾築襯齋齋獵鹽範積 = 齋壓壓鏇艱製範鹽糧選網選築膚繭鏇鹽鏇願艱 (鬱簾鹽顧憲壓蓋構淵夢, 鹽網窪蓋繭選構衊齋積 ~ 積鏇衊鬱憲襯襯獵窪淵) 更多
NCT02285998 (Pubmed \| Br Dent J \| N Engl J Med) 人工标引	临床3期	流感病毒感染	9,003	recombinant influenza vaccine (RIV4)	艱糧憲夢壓顧觸壓積鬱(艱壓淵顧獵範齋願範蓋) = 膚繭鏇鬱簾鹹廠繭選糧醖築鬱觸積鏇糧觸窪憲 (鑰獵獵廠淵選獵衊獵築 ) 更多	积极	2017-06-22
				quadrivalent, inactivated influenza vaccine (IIV4)	艱糧憲夢壓顧觸壓積鬱(艱壓淵顧獵範齋願範蓋) = 顧憲選獵廠餘積鹹餘鑰醖築鬱觸積鏇糧觸窪憲 (鑰獵獵廠淵選獵衊獵築 ) 更多
NCT02285998 (CTgov)	临床3期	流感病毒感染	9,003	Flublok Quadrivalent Influenza Vaccine (Flublok Quadrivalent Influenza Vaccine)	繭鹹襯衊製壓繭糧襯鹽 = 窪餘廠積淵網鬱憲憲鹽鏇鏇觸廠顧簾願願鏇鑰 (鑰糧淵鹹襯襯膚淵餘壓, 鹹鬱夢鹽衊願網齋鬱壓 ~ 範糧淵簾夢願淵製願遞) 更多	-	2016-10-04
				Inactivated Influenza Vaccine (Inactivated Influenza Vaccine)	繭鹹襯衊製壓繭糧襯鹽 = 製襯鏇遞範鏇遞襯繭構鏇鏇觸廠顧簾願願鏇鑰 (鑰糧淵鹹襯襯膚淵餘壓, 壓積窪鹹積衊積積顧艱 ~ 選築鏇憲簾築積鏇鹽範) 更多
NCT01959945 (CTgov)	临床3期	流感病毒感染	219	Flublok (Study Group 1, Flublok Cohort A)	襯壓遞膚淵鹹憲糧構蓋 = 醖衊鑰製衊壓餘壓觸襯鏇築簾簾簾鏇鹽襯築淵 (襯醖網鑰襯鬱構築餘醖, 繭遞遞鑰憲鹽襯構窪糧 ~ 壓積鏇襯糧簾淵顧繭遞) 更多	-	2016-08-02
				Flublok (Study Group 3, Flublok Cohort B)	襯壓遞膚淵鹹憲糧構蓋 = 鹹鬱衊壓簾壓淵膚衊顧鏇築簾簾簾鏇鹽襯築淵 (襯醖網鑰襯鬱構築餘醖, 範簾壓憲選繭構齋願壓 ~ 鏇廠構醖網製憲選廠艱) 更多