This study will determine the functional status of the nasal immune environment with LAIV exposure in COPD persons with frequent exacerbations (defined as individuals with two or more episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months) and COPD persons without frequent exacerbations to determine acute exacerbation of COPD (AECOPD)-associated dysfunction in a) cytokines and immune effector cells of the nasal mucosa and b) viral replication. The investigators hypothesize that: 1) COPD frequent exacerbators, compared to COPD infrequent exacerbators, will demonstrate altered mucosal immune responses to LAIV exposure, and 2) COPD frequent exacerbators, compared to COPD infrequent exacerbators, will demonstrate increased markers of influenza viral replication after LAIV exposure.

开始日期2022-10-03

申办/合作机构

The University of North Carolina at Chapel Hill

[+1]

CTRI/2021/11/037859

/ Not yet recruiting临床3期IIT

Study of humoral and cellular immune responses to influenza vaccinein healthy adult volunteers. - NIL

开始日期2021-11-15

申办/合作机构-

EUCTR2019-001186-33-ES

/ Unknown status临床4期

Clinical trial, phase IV, randomized, double-blind, controlled, in children aged 12 to 35 months, of the vaccine against seasonal influenza to estimate efficacy against influenza and other respiratory infections - VIGIRA

开始日期2019-09-27

申办/合作机构

Fisabio Foundation

100 项与 Influenza vaccine live(MedImmune LLC) 相关的临床结果

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100 项与 Influenza vaccine live(MedImmune LLC) 相关的转化医学

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100 项与 Influenza vaccine live(MedImmune LLC) 相关的专利（医药）

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1,534

项与 Influenza vaccine live(MedImmune LLC) 相关的文献（医药）

2025-12-31·Human Vaccines & Immunotherapeutics

Influenza vaccine effectiveness against medically-attended influenza infection in 2023/24 season in Hangzhou, China

Article

作者: Wang, Zhe ; Niu, Beidi ; Zhang, Ke ; Lei, Hao ; Sun, Zhou ; Liu, Yan ; Zhao, Gang ; Du, Shengqiang ; Yang, Shigui ; Wang, Yaojing ; Zhao, Shi ; Che, Xinren

From 2020, influenza viruses circulation was largely affected by the global coronavirus disease (COVID-19) pandemic, notably leading to the extinction of the B/Yamagata lineage and raising questions about the relevance of the quadrivalent influenza vaccine, which includes this lineage. Evaluating vaccine effectiveness (VE) against influenza infections is important to inform future vaccine programs. A test-negative case-control study was conducted in five tertiary hospitals in Hangzhou, the capital city of Zhejiang province, China, enrolling medically-attended patients aged >6 months who presented with influenza-like illness (ILI) from October 1, 2023, to March 31, 2024. The VE was estimated using multivariate logistic regression models adjusted for sex, age, influenza detection methods, and influenza testing timing. Of the 157,291 medically-attended ILI participants enrolled 56,704 (36%) tested positive for influenza. Adjusted overall VE against any medically-attended influenza infection was 48% (95% Confidence interval [CI]: 46%-51%). The overall VE of the trivalent inactivated influenza vaccine (IIV3) was 59% (95% CI: 50%-66%), followed by the trivalent live attenuated vaccine (LAIV3) (VE = 53%, 95% CI: 42%-62%) and quadrivalent inactivated influenza vaccine (IIV4) (VE = 47%, 95% CI: 45%-50%). IIV3 provided even better protection against medically-attended influenza B infection than IIV4 (VE = 87%, 95% CI: 81%-92% for IIV3 versus VE = 53%, 95% CI: 50%-57% for IIV4). In the 2023/24 season in Hangzhou, China, the influenza vaccine offered moderate protection during a major epidemic. The results supported the World Health Organization recommendation to exclude the B/Yamagata lineage antigen in quadrivalent influenza vaccines in 2023.

2025-02-01·Vaccine

Mucosal vaccination against SARS-CoV-2 using recombinant influenza viruses delivering self-assembling nanoparticles

Article

作者: Vu, Mai N ; Koutsakos, Marios ; Juno, Jennifer A ; Pilapitiya, Devaki ; Wheatley, Adam K ; Lee, Wen Shi ; Kent, Stephen J ; Kelly, Andrew ; Tan, Hyon-Xhi ; Webster, Rosela H

Recombinant influenza viruses are promising vectors that can bolster antibody and resident lymphocyte responses within mucosal sites. This study evaluates recombinant influenza viruses with SARS-CoV-2 RBD genes in eliciting mucosal and systemic responses. Using reverse genetics, we generated replication-competent recombinant influenza viruses carrying heterologous RBD genes in monomeric, trimeric, or ferritin-based nanoparticle forms. Following intranasal immunisation, mice developed potent serological anti-RBD responses, with ferritin nanoparticles superseding monomeric or trimeric RBD responses. While parenteral and mucosal immunisation elicited robust anti-RBD IgG in serum, mucosal immunisation seeded respiratory IgA, RBD-specific lung-resident memory and germinal centre (GC) B cells. In animals with prior intramuscular vaccination, intranasal boosting with recombinant influenza vectors augmented mucosal IgG, IgA, GC and memory B cells, and SARS-CoV-2 lung neutralising titres. Recall of RBD-specific memory B cells via antigen re-exposure in the lung increased antibody-secreting cells in the lung-draining lymph nodes, with maintenance of lung GC B cells. Recombinant influenza-based vaccines effectively deliver highly immunogenic self-assembling nanoparticles, generating antibodies and B cells in the respiratory mucosa. This strategy provides a tractable pathway to augment lung-localised responses against recurrent respiratory viral infections.

2025-01-01·American Journal of Preventive Medicine

Exogenous Increases in Basic Income Provisions Increase Preventive Health-Seeking Behavior: A Quasi-Experimental Study

Article

作者: Motta, Matt ; Haglin, Kathryn

INTRODUCTIONUniversal Basic Income (UBI) policies have the potential to promote a wide range of public health objectives by providing those who qualify with direct cash payments. One overlooked mechanism of particular importance to health researchers is the possibility that guaranteed income might increase consultation of primary and preventive care (e.g., annual doctors' visits; regular vaccination against infectious disease) by providing people with both the time and monetary resources to do so, thereby improving general health.METHODSThis study assesses the effects of an exogenous shock to Alaska's UBI payments to all state residents: a 2022 decision to reclassify dividend "energy relief" provisions as nontaxable (thereby increasing payments by approximately $2,000 inflation-adjusted dollars). It estimates quasi-experimental treatment effects (in 2022 vs. 2021) via mixed linear probability models that compare pre/post policy change in primary care seeking behavior in Alaska vs. the US adult population; controlling for respondent-level fixed effects and state-level random effects. Data were collected in 2021-2022, and analyzed in 2024.RESULTSThe likelihood that Alaskans sought primary care postreform (relative to beforehand) increased by 6pp, which was significantly greater than the same difference (2pp) observed across all other (non-UBI) US States (∆=4pp, p<0.01). The study provides suggestive evidence that comparatively fewer Alaskans had difficulty affording primary care during this period, with less-consistent evidence of increased flu vaccine uptake.CONCLUSIONSEnhanced UBI payments ought to be thought about as a form of health policy, as they have the potential to advance a wide range of health objectives related to preventive care.

180

项与 Influenza vaccine live(MedImmune LLC) 相关的新闻（医药）

2025-01-19

·药明康德

疾病控制率达90%的创新疗法；靶点作用率达95%的PI3Kα共价抑制剂…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 多肽偶联药物（PDC）AVA6000在治疗唾液腺癌（SGC）患者的1a期临床试验中获得积极数据，疾病控制率（DCR）达90%。 2. 蛋白降解药物BHV-1400在首个人体临床试验中获得积极结果，在最低剂量下只需一次注射，就可在4小时内将致病抗体水平降低60%。 3. PI3Kα共价抑制剂TOS-358在一项1期临床试验中对PI3Kα的靶点作用率达到95%。药明康德内容团队整理 AVA6000：公布1期临床试验数据 Avacta Therapeutics公司宣布，其在研多肽偶联药物AVA6000在治疗唾液腺癌患者的1a期临床试验中获得积极数据。唾液腺癌是一种在转移性阶段尚无标准治疗方案的疾病。AVA6000是Avacta研发管线中的首个多肽偶联药物，由阿霉素（doxorubicin）与Avacta专有的pre|CISION多肽偶联而成，该多肽可在肿瘤微环境中由成纤维细胞激活蛋白-α（FAP）特异性切割。FAP在大多数实体瘤中，与健康组织相比表达水平显著升高。Avacta的多肽偶联药物利用这一特征在肿瘤微环境中特异性释放活性药物，从而降低系统暴露和毒性，为患者提供最佳治疗效果。此次公布的数据显示，AVA6000在唾液腺癌患者中实现了显著且具有临床意义的肿瘤缩小。在接受250 mg/m²及以上剂量治疗的10名唾液腺癌患者中，DCR达90%，5名患者肿瘤显著缩小，其中包括一例部分缓解（PR，肿瘤缩小45%）和四例轻微缓解（MR，肿瘤缩小10%-19.5%）。安全性方面，在每两周一次和每三周一次两个剂量组中，AVA6000的耐受性良好，与常规剂量阿霉素相比，其血液学和心脏毒性明显降低。目前尚未在任一剂量组中确定最大耐受剂量（MTD）。 BHV-1400：公布1期临床试验的初步数据 Biohaven公司公布了其蛋白降解药物管线中的双特异性分子BHV-1400的最新结果。BHV-1400是一款基于耶鲁大学（Yale University）的MoDE技术的双特异性分子，它的一端与半乳糖缺乏型IgA1（Gd-IgA1）抗体结合，另一端与肝细胞表面的去唾液酸糖蛋白受体（ASGPR）结合。ASGPR介导肝细胞通过内吞过程，将靶点蛋白吞入细胞内进行降解。IgA肾病是由于Gd-IgA1的过度生产造成的，BHV-1400通过降低血液循环和肾脏中的Gd-IgA1水平，有望从根源治疗IgA肾病。此次公布的初步数据显示，BHV-1400在首个人体临床试验中获得积极结果，在最低剂量下只需一次注射，就可在4小时内将致病抗体水平降低60%。在某些患者中，观察到在8小时内将Gd-IgA1水平降低70%。此外，Gd-IgA1水平的降低在单次注射后可维持数天。安全性方面，迄今为止，BHV-1400在1期临床试验中的安全性和耐受性良好，未发现具有临床意义的先天和适应性免疫力的变化，并且未观察到剂量限制性毒性。这项研究将继续提高BHV-1400的剂量，探索降低Gd-IgA1水平的范围。基于该研究的积极结果，该公司还计划直接启动关键性临床试验，评估BHV-1400治疗IgA肾病的疗效和安全性。 ▲BHV-1400快速降低Gd-IgA1水平（图片来源：Biohaven公司官网） TOS-358：公布1期临床试验数据 Totus Medicines公司公布了其在研PI3Kα共价抑制剂TOS-358的1期临床试验数据。TOS-358是一款具高度特异性、强效的PI3Kα抑制剂，可在临床前模型中实现近100%的PI3Kα抑制，诱导带有PI3Kα突变的异种移植实体瘤的细胞死亡，包含结直肠癌、肺癌、乳腺癌、卵巢癌、食管癌、头颈癌，且几乎没有观察到非靶向抑制。此次公布的研究结果表明，TOS-358在低至5 mg每日两次（BID）的剂量下具有泛突变临床活性，对PI3Kα的靶点作用率达到95%，且观察到未经确认的完全缓解（CR）。安全性方面，未报道3/4级毒性。值得注意的是，几名接受给药的患者现在已超过6个月未发生进展。在成功完成1期剂量递增研究后，该公司现在启动了一项扩展研究，针对乳腺癌、子宫内膜癌、尿路上皮癌和头颈癌。 ORIC-944：公布1b期联合治疗试验数据 ORIC Pharmaceuticals公司公布了其选择性PRC2别构抑制剂ORIC-944联用阿帕鲁胺治疗转移性去势抵抗性前列腺癌（mCRPC）的1b期临床试验数据。截至2024年12月10日的数据，6例患者中有3例达到确认的PSA50应答（即PSA水平降低50%），其中2例达到确认的PSA90应答。所有PSA应答均维持≥12周，其中包括一例在38周时仍然持续的、确认的PSA90应答。 Soquelitinib：公布1期临床试验的中期数据 Corvus Pharmaceuticals公司公布了其小分子白细胞介素-2诱导的T细胞激酶（ITK）抑制剂soquelitinib用于治疗中度至重度特应性皮炎的1期临床试验的新中期数据。ITK是一种主要表达于T细胞中的酶，在T细胞和自然杀伤（NK）细胞的免疫功能中起重要作用。通过抑制ITK，soquelitinib有望抑制自身免疫和炎症反应。此次公布的结果显示，与安慰剂相比，soquelitinib治疗组在研究者总体评估（IGA）评分为0/1（皮肤症状清除或几乎清除）和湿疹面积和严重度指数较基线减少75%（EASI 75）这些临床终点方面显示出良好的疗效特征。在soquelitinib组的19例患者中，26%的患者达到IGA 0/1，37%的患者达到EASI 75。在安慰剂组的7例患者中，没有人达到IGA 0/1，也没有人达到EASI 75。安全性方面，未观察到明显的安全问题，也未发现临床上显著的实验室检测异常。 ▲治疗第28天达到终点IGA 0/1、EASI 75的患者占比（图片来源：参考资料[4]） ISM5411：公布两项1期临床试验数据英矽智能（Insilico Medicine）公司宣布，其自主研发的候选药物ISM5411已完成在澳大利亚和中国开展的两项1期研究，并取得了积极的初步结果。ISM5411是一种潜在用于治疗炎症性肠病（IBD）的小分子抑制剂，靶向PHD1/2靶点且具有新颖的分子结构，该候选药物设计和优化得到了英矽智能生成化学平台Chemistry42的支持。此次公布的结果显示，在所有剂量组中ISM5411均表现出良好的安全性和耐受性，并初步验证了肠道限制性药代动力学（PK）特征。基于1期临床试验的积极结果，英矽智能预计将于2025年下半年启动一项评估ISM5411在活动性溃疡性结肠炎患者中的2期临床试验。 MBX 1416：公布1期临床试验数据 MBX Biosciences公司公布了在健康成年受试者中开展的MBX 1416单剂量递增和多剂量递增临床试验的积极结果。MBX 1416是一种长效胰高血糖素样肽1（GLP-1）受体拮抗剂，用于治疗减肥后的低血糖症（PBH）。MBX 1416采用MBX公司新颖、专有的精准内分泌肽（PEP）平台设计，旨在防止PBH患者发生严重低血糖，使他们能够过上更健康、更独立的生活。此次公布的结果显示，MBX 1416通常安全性和耐受性良好，并且具有良好的药代动力学特征，支持每周一次给药。基于这些结果，该公司计划于2025年下半年在PBH患者中启动一项2期研究，以进一步优化剂量。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Avacta Announces Positive New Data from the AVA6000 Phase 1 trial Demonstrating Clinically Meaningful Tumor Shrinkage in Patients with Salivary Gland Cancers. Retrieved January 16, 2025, from https://www.globenewswire.com/news-release/2025/01/16/3010665/0/en/Avacta-Announces-Positive-New-Data-from-the-AVA6000-Phase-1-trial-Demonstrating-Clinically-Meaningful-Tumor-Shrinkage-in-Patients-with-Salivary-Gland-Cancers.html [2] Biohaven Highlights Portfolio Progress, Innovation, and Anticipated Milestones at the 43rd Annual J.P. Morgan Healthcare Conference; Reports Positive Degrader Data with Rapid, Deep, and Selective Lowering of Galactose-Deficient IgA1 with Next Generation Potential Therapy for IgA Nephropathy. Retrieved January 14, 2025, from https://www.prnewswire.com/news-releases/biohaven-highlights-portfolio-progress-innovation-and-anticipated-milestones-at-the-43rd-annual-jp-morgan-healthcare-conference-reports-positive-degrader-data-with-rapid-deep-and-selective-lowering-of-galactose-deficient-ig-302349336.html [3] Totus Medicines Announces Successful Completion of a Phase 1 Dose-Escalation Study and Initiation of an Expansion Trial Evaluating TOS-358, a Covalent PI3Ka Selective Therapy for the Treatment of Select Solid Tumors and Appoints Zelanna Goldberg as Chief Medical Officer. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/10/3007658/0/en/Totus-Medicines-Announces-Successful-Completion-of-a-Phase-1-Dose-Escalation-Study-and-Initiation-of-an-Expansion-Trial-Evaluating-TOS-358-a-Covalent-PI3Ka-Selective-Therapy-for-th.html [4] Corvus Pharmaceuticals Announces Data from Cohort 2 of Placebo-Controlled Phase 1 Clinical Trial of Soquelitinib for Atopic Dermatitis. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008374/0/en/Corvus-Pharmaceuticals-Announces-Data-from-Cohort-2-of-Placebo-Controlled-Phase-1-Clinical-Trial-of-Soquelitinib-for-Atopic-Dermatitis.html [5] ORIC® Pharmaceuticals Provides Early Phase 1b Combination Data for ORIC-944, Operational Highlights for 2024, and Anticipated Upcoming Milestones. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008495/0/en/ORIC-Pharmaceuticals-Provides-Early-Phase-1b-Combination-Data-for-ORIC-944-Operational-Highlights-for-2024-and-Anticipated-Upcoming-Milestones.html [6] 英矽智能公布炎症性肠病药物ISM5411两项I期临床试验的积极结果. Retrieved January 17, 2025, from https://www.prnasia.com/story/474986-1.shtml [7] MBX Biosciences Announces Positive Phase 1 Topline Results for MBX 1416 for the Treatment of Post-bariatric Hypoglycemia. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/07/3005223/0/en/MBX-Biosciences-Announces-Positive-Phase-1-Topline-Results-for-MBX-1416-for-the-Treatment-of-Post-bariatric-Hypoglycemia.html [8] Mersana Therapeutics Announces Positive Initial Clinical Data from Phase 1 Clinical Trial of Emiltatug Ledadotin (XMT-1660); Initiation of Expansion in Triple Negative Breast Cancer. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/10/3007493/0/en/Mersana-Therapeutics-Announces-Positive-Initial-Clinical-Data-from-Phase-1-Clinical-Trial-of-Emiltatug-Ledadotin-XMT-1660-Initiation-of-Expansion-in-Triple-Negative-Breast-Cancer.html [9] Axcynsis Therapeutics Receives FDA Clearance for IND Application of AT03-65, a Differentiated CLDN6-Targeting ADC, Powered by AxcynDOT™ Technology. Retrieved January 17, 2025, from https://www.prnewswire.com/news-releases/axcynsis-therapeutics-receives-fda-clearance-for-ind-application-of-at03-65-a-differentiated-cldn6-targeting-adc-powered-by-axcyndot-technology-302350114.html [10] Ocugen, Inc. Announces Positive 2-Year Data Across Multiple Mutations from Phase 1/2 Clinical Trial of OCU400 —A Novel Modifier Gene Therapy for Retinitis Pigmentosa. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008252/0/en/Ocugen-Inc-Announces-Positive-2-Year-Data-Across-Multiple-Mutations-from-Phase-1-2-Clinical-Trial-of-OCU400-A-Novel-Modifier-Gene-Therapy-for-Retinitis-Pigmentosa.html [11] Verismo Therapeutics Announces First Patient Infused in Phase 1 CELESTIAL-301 Clinical Trial of SynKIR™-310. Retrieved January 17, 2025, from https://www.prnewswire.com/news-releases/verismo-therapeutics-announces-first-patient-infused-in-phase-1-celestial-301-clinical-trial-of-synkir-310-302347464.html [12] Caribou Biosciences Initiates the CB-010 GALLOP Phase 1 Trial in Lupus and Provides Outlook for Multiple Clinical Datasets in 2025. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008079/0/en/Caribou-Biosciences-Initiates-the-CB-010-GALLOP-Phase-1-Trial-in-Lupus-and-Provides-Outlook-for-Multiple-Clinical-Datasets-in-2025.html [13] Arcturus Therapeutics Announces Initiation of Phase 1 H5N1 Flu Vaccine Trial. Retrieved January 17, 2025, from https://ir.arcturusrx.com/news-releases/news-release-details/arcturus-therapeutics-announces-initiation-phase-1-h5n1-flu [14] Korro Bio Announces Dosing of First Participants in REWRITE Phase 1/2a Study of KRRO-110 for Alpha-1 Antitrypsin Deficiency and Provides Pipeline Update. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/13/3008445/0/en/Korro-Bio-Announces-Dosing-of-First-Participants-in-REWRITE-Phase-1-2a-Study-of-KRRO-110-for-Alpha-1-Antitrypsin-Deficiency-and-Provides-Pipeline-Update.html [15] NextCure Announces First Patient Dosed in the Phase 1 Study of LNCB74 (B7-H4 ADC) as Therapeutic for Treating Multiple Cancers. Retrieved January 17, 2025, from https://ir.nextcure.com/news-releases/news-release-details/nextcure-announces-first-patient-dosed-phase-1-study-lncb74-b7 [16] LAVA Doses First Patient in Phase 1 LAVA-1266 Study in Hematological Cancers. Retrieved January 17, 2025, from https://www.globenewswire.com/news-release/2025/01/10/3007674/0/en/LAVA-Doses-First-Patient-in-Phase-1-LAVA-1266-Study-in-Hematological-Cancers.html [17] Context Therapeutics Announces First Patient Dosed in the Phase 1 Clinical Trial of CTIM-76. Retrieved January 17, 2025, from https://www.globenewswire.com/de/news-release/2025/01/14/3009673/0/en/Context-Therapeutics-Announces-First-Patient-Dosed-in-the-Phase-1-Clinical-Trial-of-CTIM-76.html [18] Ocugen, Inc. Announces First Patient Dosed in Phase 1 Clinical Trial of OCU200—a Novel Integrin-Targeting Biologic for Diabetic Macular Edema. Retrieved January 17, 2025, from https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-first-patient-dosed-phase-1-clinical-trial [19] ProMIS Neurosciences Initiates Phase 1b Clinical Trial (PRECISE-AD) in Alzheimer’s Disease. Retrieved January 17, 2025, from https://www.promisneurosciences.com/news-media/press-releases/detail/236/promis-neurosciences-initiates-phase-1b-clinical-trial [20] Aptose Announces First AML Patients Dosed with Tuspetinib Triplet Frontline Therapy in TUSCANY Trial. Retrieved January 17, 2025, from https://www.aptose.com/news-media/press-releases/detail/307/aptose-announces-first-aml-patients-dosed-with-tuspetinib [21] ORYZON announces first patient dosed in NCI-sponsored iadademstat in combination with venetoclax and azacitidine clinical trial in first line acute myeloid leukemia. Retrieved January 17, 2025, from https://www.oryzon.com/en/news-events/news/oryzon-announces-first-patient-dosed-nci-sponsored-iadademstat-combination [22] 한미약품-GC녹십자, ‘파브리병’ 국내 1/2상 IND 승인. Retrieved January 17, 2025, from https://www.biospectator.com/news/view/24043 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床结果临床1期多肽偶联药物

2025-01-09

·生物制品圈

mRNA专利解析 | 辉瑞季节性流感疫苗PF-07252220

导读：流感病毒感染宿主包括人类和动物，可造成轻度至重度和致命性疾病。尽管目前有多款流感疫苗获批上市，但由于流感病毒广泛的抗原变异，容易导致减弱的保护效力。且当前流感疫苗多借助活病毒培养，对生产环境要求极高。鉴于mRNA-LNP疫苗在生产周期和免疫应答等方面的独特优势，药企早期就布局了流感mRNA疫苗的开发。 PF-07252220是辉瑞开发的一款基于修饰mRNA的季节性流感疫苗，以针对甲型H1N1和乙型/Yamagata流感为基础，提供单价、二价和四价制剂形式。本期文章，菌菌将详细解析辉瑞关于PF-07252220的专利。 01 辉瑞mRNA流感疫苗PF-07252220简介 PF-07252220是辉瑞开发的一款mRNA流感疫苗，编码甲型或乙型流感病毒来源的血凝素（HA）抗原，以单价、二价或四价形式被开发。PF-07252220在早期临床试验中显示出良好的安全性、耐受性和免疫原性。然而其III期临床数据显示出了不同年龄队列的差异，PF-07252220在18-64岁的参与者中体现了免疫疗效，达到了非劣效性和优效性的主要终点。但在65岁及以上的成年人中未达到主要终点（与上市疫苗相比的非劣效性指标）。图示 PF-07252220 III期试验关键结果 02 辉瑞mRNA流感疫苗PF-07252220序列设计 2.1 mRNA编码序列 PF-07252220编码序列的选择是基于2021-2022年北半球流感季节的推荐，是以下四种流感毒株来源的HA糖蛋白的全长密码子优化序列： nWisconsin modRNA (Wisc2019 HA) nPhuket modRNA (Phuk2013 HA) nWashington modRNA (Wash2019 HA) nCambodia modRNA (Camb2020 HA) 基于上述mRNA，PF-07252220具有5种使用形式，包括4种单价mRNA疫苗、以及由4种mRNA组合使用的二价或四价疫苗。图示 mRNA疫苗抗原推荐（2021-2022年北半球） 2.2 mRNA非编码序列非编码区序列UTR序列和poly(A)尾在mRNA稳定性和翻译过程发挥重要作用，也是mRNA序列设计的重点。目前已衍生出3种常用的UTR设计策略：第一种是直接选取高表达的人类基因UTR，例如人alpha珠蛋白mRNA的UTR。使用GCCACCAUG替换了ACCAUG；第二种是通过指数富集（SELEX）的方式来实现UTR的系统演化，已成功在Moderna新冠疫苗中得以验证；第三种是选择病毒来源的UTR，这一策略常用于自复制mRNA的设计。可供参考的poly(A)尾巴的设计原则主要有2种：一种是采用纯腺苷组成的尾巴，长度一般在100-120 nt；另一种是BioNTech/辉瑞创新发现的分段式poly(A)，在纯腺苷中间插入连接序列，能够在提高mRNA稳定性的同时保持其翻译效率。辉瑞在专利中公开了mRNA流感疫苗的非编码区序列，其序列特征如下： nmRNA流感疫苗的5’ UTR长度为54-nt，来源于人α -珠蛋白，并在此基础上对其Kozak序列进行了优化，将ACCAUG替换为GCCACCAUG； nmRNA流感疫苗的3’ UTR长度为295-nt，由两个序列元件组成，分别来自氨基末端增强子分裂蛋白（AES）和线粒体12S核糖体RNA（12S rRNA），以确保RNA的稳定性和高水平的蛋白表达。 n与新冠mRNA疫苗BNT162b2一致，辉瑞在流感疫苗的设计中也采用了分段式的poly(A)尾巴，总体长度为110 nt的poly(A)由30个腺苷、10个非纯A连接子（GCATATGACT）、以及下游的70个腺苷组成。图示辉瑞mRNA流感疫苗的UTR序列和poly(A)序列 2.3 其他修饰 PF-07252220中包含的mRNA是一种经核苷酸修饰的mRNA，其5’端包含帽类似物，结构为m2-7,3’-OGppp (m1-2’-O)ApG，即Cap1。 03 辉瑞mRNA流感疫苗PF-07252220递送系统编码不同毒株来源的HA抗原蛋白的一种或多种mRNA被包封在一个脂质纳米颗粒（LNP）中。专利公开的LNP组分为可电离阳离子脂质ALC-0315、磷脂DSPC、胆固醇和PEG脂质ALC-0159。其LNP制剂溶解于含300 mM蔗糖的10 mM Tris缓冲液（pH 7.4）中。 ALC-0315与ALC-0159是首次用于辉瑞新冠mRNA疫苗的新型脂质，专利归Acuitas所有，辉瑞/BioNTech通过与Acuitas合作获得了使用许可。图示阳离子脂质体ALC-0315的结构式图示 PEG脂质ALC-0159的结构式 04 结语从专利公开信息来看，辉瑞的流感疫苗管线PF-07252220在序列设计和递送系统两方面与新冠疫苗BNT162b2一致。5’ UTR序列，二者均基于人α -珠蛋白mRNA来源的UTR进行了Kozak序列的优化；3’ UTR序列均选择了AES和12S rRNA的串联形式；poly(A)尾同样是长度为110 nt的分段式尾巴30A + 10(GCAUAUGACU) + 70A。脂质递送系统方面，辉瑞的流感疫苗和新冠疫苗均选择了基于ALC-0315与ALC-0159两种新型脂质的配方。辉瑞针对新冠和季节性流感mRNA疫苗的设计，无疑体现了mRNA技术的灵活性和平台性，仅需替换编码区域序列，即可用于表达任意所需的蛋白，实现预防或治疗疾病的目的。参考文献 [1] Pfizer. Immunogenic composition against influenza. Patent. US10716846B2 / WO2022234417A1. [2] Pfizer Initiates Phase 3 Study of mRNA-Based Influenza Vaccine. Retrieved September 14, 2022 from https://www.pfizer.com/news/press-release/press-release-detail/pfizer-initiates-phase-3-study-mrna-based-influenza-vaccine. [3] Carascal MB, Pavon RDN, Rivera WL. Recent Progress in Recombinant Influenza Vaccine Development Toward Heterosubtypic Immune Response [published correction appears in Front Immunol. 2022 Jun 13. 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。

信使RNA疫苗临床3期上市批准

2025-01-08

·Endpoints

Pfizer, GSK add risk of Guillain-Barré to RSV vaccine labels at FDA's request

Pfizer and GSK’s RSV vaccines have a new warning at the request of the FDA, relaying an increased risk of Guillain-Barré syndrome within the first 42 days post-vaccination. The agency said in a bulletin Tuesday that “the overall body of evidence suggests increased risks of GBS with Abrysvo and Arexvy, but that available evidence is insufficient to establish a causal relationship.” The FDA approved updated labels for both companies on Monday. The neurological autoimmune condition is marked by tingling or weakness in people’s arms and legs, and sometimes arise within weeks after an infection. GSK said in a statement that it has its own ongoing safety studies, including on the risk of GBS, but that it remains “confident in the benefit-risk profile of Arexvy for the prevention of RSV-LRTD.” Pfizer reiterated the FDA’s conclusion in a statement. Key data underpinning the decision came from an FDA post-marketing study assessing the risk of GBS across the two vaccines, finding there were nine excess cases of the condition per million doses administered of Pfizer’s Abrysvo, and seven excess cases per million doses administered of GSK’s Arexvy to adults 65 and older. The FDA previously presented the study findings at the CDC’s Advisory Committee on Immunization Practices in October, which showed a statistically significant risk increase for GSK’s vaccine but not Pfizer’s, given that it had fewer doses administered in the study. Still, the agency concluded then that Pfizer’s shot came with an elevated risk. FDA presenters concluded then that the risk of GBS post-vaccination of either shot remained “rare” and that the risks didn’t deviate based on whether people received other vaccines at the same time. An FDA reviewer told the CDC panel that it could not break down the risk by age based on the sample size of the post-marketing study. Moderna, which had its RSV vaccine approved after the post-marketing study began, was not included in the FDA’s label change. At the time of ACIP’s October meeting, no cases of GBS had been found within 42 days of vaccination in Moderna’s clinical trials and post-licensure surveillance data wasn’t yet available. Other vaccines have had varying risks associated with GBS, including the flu vaccines which have a small, one-to-two-case risk increase per million doses of flu vaccine administered. For Johnson & Johnson’s one-shot Covid-19 vaccine, the GBS risk was 11 times higher within the first 42 days than the Pfizer or Moderna options. The label warning follows a bleak second vaccination season for RSV makers, marked by tightened guidance, significantly less uptake and now a safety warning. Prescription data through the middle of December found that uptake was roughly 50% less than through the same period in 2023, according to Jefferies research.

疫苗信使RNA临床研究

100 项与 Influenza vaccine live(MedImmune LLC) 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Influenza vaccine live(MedImmune LLC)	J07BB03	-

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	列支敦士登	AstraZeneca AB	2024-06-03
流感病毒感染	欧盟	AstraZeneca AB	2024-06-03
流感病毒感染	冰岛	AstraZeneca AB	2024-06-03
流感病毒感染	挪威	AstraZeneca AB	2024-06-03

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
流感病毒感染	临床2期	冰岛	MedImmune LLC	2011-01-27
流感病毒感染	临床2期	列支敦士登	MedImmune LLC	2011-01-27
流感病毒感染	临床前	欧盟	MedImmune LLC	2011-01-27
流感病毒感染	临床前	挪威	MedImmune LLC	2011-01-27
哮喘	临床前	比利时	MedImmune LLC	2002-10-01
反复呼吸道感染	临床前	西班牙	MedImmune LLC	2002-10-01

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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


NCT04110366 (Flu-M3, CTgov)	N/A	流感病毒感染	48	Live attenuated influenza vaccine (Live Attenuated Influenza Vaccine)	憲鹹醖構餘鑰鬱壓夢網(鏇鬱廠願壓選築窪顧醖) = 顧顧鬱鑰簾觸襯鑰壓襯觸鑰鹹廠膚範憲醖膚選 (築願積築觸鏇餘艱獵繭, 艱蓋選鹹窪壓齋繭繭觸 ~ 積遞鑰齋網糧鹽製廠構) 更多	-	2021-12-06
				Vehicle Control (Mucosal Immune Stability Cohort)	獵築齋廠淵膚鹽醖繭構(製築顧鏇製選鹹顧糧獵) = 築製餘願網鏇網鑰艱廠壓餘餘艱憲鹹構糧獵艱 (鹽願壓繭憲網齋糧製襯, 膚鏇襯膚積選憲觸餘膚 ~ 選鹽積廠築製簾蓋鹽願) 更多
NCT01194297 (CTgov)	临床4期	流感病毒感染	3	Inactivated influenza vaccine (Inactivated Influenza Vaccine)	(網鬱鑰醖壓窪膚鬱製築) = 窪願遞艱築艱製蓋獵願窪鑰築醖膚鑰遞齋顧選 (糧膚壓壓積顧窪鏇淵製, 鹹鑰鏇簾鹽製壓獵淵鑰 ~ 獵齋積艱窪遞鬱廠獵繭) 更多	-	2014-08-22
				Live attenuated influenza vaccine (Live Attenuated Influenza Vaccine)	(網鬱鑰醖壓窪膚鬱製築) = 糧衊糧築膚願繭遞鏇鬱窪鑰築醖膚鑰遞齋顧選 (糧膚壓壓積顧窪鏇淵製, 簾糧襯夢選齋夢簾憲膚 ~ 蓋積廠窪遞憲齋蓋積蓋) 更多
NCT00344305 (CTgov)	临床2期	流感病毒感染	200	Trivalent influenza virus vaccine live, intranasal (Cohort 1: Participants Between 6 to < 24 Months Age)	淵襯獵膚鹽憲蓋鹹衊築(鹽願衊壓壓糧糧餘觸糧) = 夢膚選範醖選築鹹積築選鏇選顧齋積膚壓製壓 (積鏇遞鬱觸夢遞網願觸, 窪憲蓋齋餘壓鏇鬱願鬱 ~ 遞範蓋簾獵鹽醖網鹽窪) 更多	-	2010-11-01
				Trivalent influenza virus vaccine live, intranasal (Cohort 2: Participants Between 24 to < 60 Months Age)	淵襯獵膚鹽憲蓋鹹衊築(鹽願衊壓壓糧糧餘觸糧) = 窪簾鹽選衊選壓築積觸選鏇選顧齋積膚壓製壓 (積鏇遞鬱觸夢遞網願觸, 鏇衊願襯窪遞衊壓淵網 ~ 蓋壓夢遞構蓋鹹廠憲艱) 更多
NCT00677820 (MI-MA182, CTgov)	临床4期	流感病毒感染	300	Trivalent influenza virus vaccine (Trivalent Influenza Virus Vaccine)	衊鏇鏇膚鬱遞衊鏇鬱遞(遞簾糧蓋鹽夢遞廠淵壓) = 糧窪衊餘衊窪鹽簾鑰觸餘淵繭蓋淵鏇壓網築窪 (鹹鑰淵鏇觸簾獵糧壓淵, 蓋鏇選窪獵壓網繭餘衊 ~ 顧鬱窪淵鏇鹽衊觸獵廠) 更多	-	2010-09-15
				Placebo (Placebo)	衊鏇鏇膚鬱遞衊鏇鬱遞(遞簾糧蓋鹽夢遞廠淵壓) = 餘衊膚鹽範夢糧製蓋艱餘淵繭蓋淵鏇壓網築窪 (鹹鑰淵鏇觸簾獵糧壓淵, 蓋積淵齋願願簾範夢網 ~ 選獵蓋獵鬱艱遞觸餘選) 更多