更新于：2024-06-20

Influenza vaccine(Seqirus GmbH)

更新于：2024-06-20

概要

研发状态

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)

+ [1]

靶点-

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

非在研适应症-

原研机构

Seqirus GmbH

在研机构

Seqirus GmbH

非在研机构

Novartis Vaccines & Diagnostics SLNovartis Pharma AG

最高研发阶段批准上市

首次获批日期

美国 (2015-11-24),

甲型流感病毒感染乙型流感病毒感染

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]

NCT05518500 / Recruiting临床4期IIT

A Deep Longitudinal Analysis of Next Generation Influenza Vaccines in Older Adults

This is a prospective, single-arm study designed to understand the mechanisms that lead to a loss of response to influenza vaccine in older adults. The investigators will recruit and longitudinally follow a cohort of 66 older adults (65 years and older) who will receive three different influenza vaccines over three annual influenza seasons. Blood samples will be collected from the participants at each of the sixteen study visits over three years. Nasal swab and stool samples will also be collected from participants at seven time-points across the study period. The study is not designed to assess safety or tolerability of the influenza vaccines administered as part of this study.

开始日期2022-08-31

申办/合作机构

The Jackson Laboratory

[+5]

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

2023-08-21·Vaccines

Advances in Adjuvanted Influenza Vaccines.

Review

作者: Shichinohe, Shintaro ; Watanabe, Tokiko

The numerous influenza infections that occur every year present a major public health problem. Influenza vaccines are important for the prevention of the disease; however, their effectiveness against infection can be suboptimal. Particularly in the elderly, immune induction can be insufficient, and the vaccine efficacy against infection is usually lower than that in young adults. Vaccine efficacy can be improved by the addition of adjuvants, and an influenza vaccine with an oil-in-water adjuvant MF59, FLUAD, has been recently licensed in the United States and other countries for persons aged 65 years and older. Although the adverse effects of adjuvanted vaccines have been a concern, many adverse effects of currently approved adjuvanted influenza vaccines are mild and acceptable, given the overriding benefits of the vaccine. Since sufficient immunity can be induced with a small amount of vaccine antigen in the presence of an adjuvant, adjuvanted vaccines promote dose sparing and the prompt preparation of vaccines for pandemic influenza. Adjuvants not only enhance the immune response to antigens but can also be effective against antigenically different viruses. In this narrative review, we provide an overview of influenza vaccines, both past and present, before presenting a discussion of adjuvanted influenza vaccines and their future.

2022-08-01·International journal of pharmaceutics

Formulation of dry powders of vaccines containing MF59 or AddaVax by Thin-Film Freeze-Drying: Towards a dry powder universal flu vaccine

Article

作者: Ross, Ted M ; Xu, Haiyue ; Cui, Zhengrong ; Uno, Naoko ; Williams Iii, Robert O ; Cano, Chris ; AboulFotouh, Khaled ; Christensen, Dale J ; Davenport, Gregory J ; Sahakijpijarn, Sawittree ; Moon, Chaeho

MF59® is an oil-in-water (O/W) nanoemulsion-based vaccine adjuvant that is often used in seasonal and pandemic influenza vaccines. We explored the feasibility of developing dry powders of vaccines adjuvanted with MF59 or AddaVax™, a preclinical grade equivalent of MF59 with the same composition and droplet size as MF59, by thin-film freeze-drying (TFFD). Liquid AddaVax alone was successfully converted to a dry powder by TFFD using trehalose as a stabilizing agent while maintaining the droplet size distribution of AddaVax after it was reconstituted. TFFD was then applied to convert liquid AddaVax-adjuvanted vaccines containing either a model antigen (e.g., ovalbumin) or mono-, bi-, and tri-valent recombinant hemagglutinin (rHA) protein-based H1 and/or H3 (universal) influenza vaccine candidates, as well as the MF59-containing Fluad® Quadrivalent influenza vaccine to dry powders. Both antigens and stabilizing agents affected the physical properties of the vaccines (e.g., mean particle size and particle size distribution) after the vaccines were subjected to TFFD. Importantly, the integrity and hemagglutination activity of the rHA antigens did not significantly change and the immunogenicity of reconstituted influenza vaccine candidates was maintained when evaluated in a mouse model. The vaccine dry powder was not sensitive to repeated freezing-and-thawing, in contrast to its liquid counterpart. It is concluded that TFFD can be applied to convert liquid vaccines containing MF59 or AddaVax to dry powders while maintaining the immunogenicity of the vaccines. Ultimately, TFFD technology may be used to prepare dry powders of multivalent universal influenza vaccines.

2022-02-01·The Lancet. Respiratory medicine1区 · 医学

Safety, immunogenicity, and efficacy of a COVID-19 vaccine (NVX-CoV2373) co-administered with seasonal influenza vaccines: an exploratory substudy of a randomised, observer-blinded, placebo-controlled, phase 3 trial

1区 · 医学

Article

BACKGROUND:

The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines.

METHODS:

We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria-with no contraindications to influenza vaccination-were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 μg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18-64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995.

FINDINGS:

Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to <65 years) was 87·5% (95% CI -0·2 to 98·4) and in the main study was 89·8% (95% CI 79·7-95·5).

INTERPRETATION:

To our knowledge, this substudy is the first to show the safety, immunogenicity, and efficacy profile of a COVID-19 vaccine when co-administered with seasonal influenza vaccines. Our results suggest concomitant vaccination might be a viable immunisation strategy.

FUNDING:

Novavax.

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

2024-05-28

·药智网

流感疫苗一夜变天

继二价HPV疫苗价格大跳水之后，四价流感疫苗也开始降价。近日，江苏省对国药集团下属的长春所、武汉所、上海所四价流感病毒裂解疫苗的供应价格进行了调整，中标价格从128元/支降到88元/支。此前，我国四价流感疫苗份额主要被华兰生物所占领，随着越来越多的四价流感疫苗获批上市，降价会抢夺更多市场份额，国内的四价流感疫苗竞争格局“一夜变天”。01跌破百元，市场格局变动流感疫苗是全球疫苗产业界的重磅品种，全球市场份额超百亿元，流感疫苗巨头赛诺菲2022年和2023全球销售额分别为29.77亿欧元（约32.1亿美元）和26.69亿欧元（约28.8亿美元），GSK的流感疫苗2022年和2023全球销售额分别为7.14亿英镑（8.8亿美元）和5.04亿英镑（6.2亿美元）。然而，由于接种意识较弱、产业供应量不足、自费接种等原因，国内流感疫苗渗透率低，截至2020年，国内流感疫苗批签发总量5765万剂次，若按照2020年末全国总人口141212万人来计算，即便当年签发的疫苗实现全部接种，全人群接种率也仅有4.08%，与发达国家以及WHO建议的流感疫苗目标接种率75%相差甚远，国内仍有巨大成长空间。近些年，随着行业持续发展以及新冠疫情的爆发等，国内民众接种疫苗的意愿大幅增强，有望提高我国流感疫苗整体渗透率。据华兴证券的测算，我国流感疫苗市场有望由2020年的64亿元增长至2025年的197亿元。目前，我国流感疫苗主要供应商包括华兰生物、金迪克生物、科兴生物、长春所、武汉所和上海所等。华兰生物是国内流感疫苗领域的领军企业，2020年华兰疫苗流感疫苗年批签发数量分别为2,315.3万剂，占比达到41.77%，居国内首位，其次是科兴生物和赛诺菲巴斯德，占比分别为19.37%和16.10%。流感疫苗种类繁多，我国批准上市的流感疫苗包括三价灭活疫苗（IIV3）、三价减毒活疫苗（LAIV3）和四价灭活疫苗（IIV4），其中IIV3和IIV4有裂解疫苗和亚单位疫苗，目前四价流感病毒疫苗是我国主要流感疫苗，2020年批签发量为3358.23万支/瓶，与2019年相比同比大幅增长246%。此前，四价流感疫苗的供应价一直维持在百元以上，以2023年北京疾控中心非免疫规划流感疫苗采购项目为例，适用于36月龄以上人群的三价流感病毒裂解疫苗的单支价格为53元—65元，四价流感病毒裂解疫苗的单支价格为128元。而近期江苏省对部分疫苗的供应价格进行了调整。其中，国药集团下属的长春所、武汉所、上海所四价流感病毒裂解疫苗中标价格从128元/支降到88元/支，跌破百元。国药集团下属的这三家的四价流感疫苗于2022年底开始陆续获批，2023年逐步投放市场，如去年6月，武汉生物制品研究所和长春生物制品研究所生产的首批四价流感病毒裂解疫苗获得批签发证明。此次国药集团率先发动价格战，受到影响最大的预计会是四价流感疫苗之王华兰疫苗，2020年华兰生物四价流感疫苗签发量为2,062.4万剂，占国内总四价流感疫苗签发量61.41%。如果华兰生物、金迪克生物等疫苗主要供应商后续不降价，国药集团势必会通过低价抢占更多市场份额，国药集团此次降价有望扩增接种人数，也给后续研发四价流感疫苗的公司一定的压力。02全球已上市流感疫苗在美国，流感疫苗接种率较高，据预计2021~2022年的流感季，6个月至17岁的儿童接种≥1剂流感疫苗的比例为57.8%，18≥岁的成年人流感疫苗接种覆盖率为49.4%，65岁以上的老年人流感疫苗接种覆盖率则达到73.9%。美国市场上主要应用的流感疫苗如表1所示，澳大利亚生物医药巨头CSL集团旗下公司Seqirus是全球流感预防领域的领导者，该公司上市的流感疫苗主要有Afluria、Fluvirin、Agriflu、Flucelvax和Fluad，都是通过肌肉注射的四价流感病毒裂解疫苗，覆盖6个月以上各个年龄层（表1）。表1 美国市场上主要应用的流感疫苗数据来源：参考文献3赛诺菲的Fluzone、Fluzone High Dose和Fluzone Intradermal应用也很广泛，Fluzone和Fluzone High Dose是通过肌肉注射的四价流感病毒裂解疫苗，Fluzone Intradermal是通过皮内注射的四价流感病毒裂解疫苗。目前，我国有超10款三价流感疫苗和超5款四价流感疫苗上市，生产厂商主要包括华兰疫苗、金迪克、科兴生物、长春所、武汉所和上海所等，大多通过肌肉注射给药。其中，长春百克生物研制的冻干鼻喷流感减毒活疫苗上市申请于2020年2月获批，采用鼻腔喷雾给药方式接种，是我国首个国产鼻喷剂型的流感减毒活疫苗，适用于3-17岁儿童和青少年人群。四价流感疫苗因比三价流感疫苗多覆盖一下乙型株而应用更广泛（表2），2018年，华兰生物自研四价流感病毒裂解疫苗上市，成为国内首批获得上市批准的四价流感病毒裂解疫苗产品，随后2022年2月，华兰生物成为首家取得四价流感疫苗（儿童剂型）的《药品注册证书》，该产品可用于6-36个月龄儿童接种，填补了国内市场空白。表2 国内部分四价流感疫苗信息数据来源：参考文献403国内在研四价流感疫苗除了已获批上市的流感疫苗，国内有多款在研的流感疫苗，大多属于四价流感疫苗，其中复星医药子公司雅立峰生物、步长制药子公司浙江天元的四价流感疫苗生产注册均已获受理，智飞生物和康润生物四价流感病毒裂解疫苗目前处于申报上市阶段，正在审评中（表3）。表3 国内部分在研四价流感疫苗数据来源：公开资料整理据不完全统计，至少有6款四价流感病毒裂解疫苗处于临床3期试验阶段，如武汉生物、中逸安科生物、康泰生物、成大生物等，其中武汉生物的四价流感病毒裂解疫苗采用MDCK细胞进行病毒培养，相比于传统的鸡胚培养具有多项优势，如生产周期更短以及不存在原材料供应不稳定的问题等。还有一些四价流感病毒裂解疫苗处于早期开发阶段，如今年3月，国内疫苗龙头公司艾美疫苗已经提交了其四价MDCK细胞流感疫苗临床试验预申请、5月欧林生物宣布其四价流感病毒裂解疫苗获国家药品监督管理局批准开展临床试验以及康泰生物公告称其四价流感病毒裂解疫苗新增6-35月龄人群临床试验申请获得受理。04结语国内人口基数大，流感疫苗接种率低，存在巨大成长空间，吸引无数药企加入布局，价格战不仅对已上市的疫苗产生影响，也对在研的流感疫苗产生影响，但是国内人口基数大，降价也会惠及更多民众，为行业大势所趋。参考文献1.市场资讯：Q3业绩大涨167%！「流感疫苗之王」的突围2.红星新闻网：国产疫苗价格大跳水！四价流感疫苗降至88元二价HPV疫苗降至63元3.https://www-cas-org.libproxy1.nus.edu.sg/zh-hans/resource/blog/covid19-flu-vaccine4.生物制品圈：深度梳理：国内外流感疫苗研究的最新动向声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 德清君转载开白 | 马老师 18996384680（同微信）商务合作 | 王存星 19922864877（同微信）阅读原文，是昨天最受欢迎的文章哦

疫苗上市批准核酸药物带量采购

2024-02-18

·药精通Bio

漫话“疫苗佐剂”

IVC2024第四届核酸疫苗与创新型疫苗论坛议程曝光点击图片查看，报名即将截止：（扫码立即领取限量免费参会入场券）前言疫苗接种无疑是人类历史上最引人注目的健康成就之一。在短短两个多世纪的时间里，疫苗使我们实现了非凡的目标，如彻底根除天花、消灭了世界大部分地区的脊髓灰质炎，并使许多传染病的死亡率和发病率大幅下降。疫苗接种政策是公共卫生的基石，人们非常重视确保接种安全有效的疫苗。疫苗的效力不仅取决于抗原成分，还取决于经常使用的佐剂，以更有效的方式刺激免疫系统。佐剂是添加到疫苗中以改善对抗原免疫反应的成分。此外，佐剂还有几个好处，如可使每剂疫苗的抗原量和疫苗接种次数减少；在某些情况下，它们还增加了抗原成分的稳定性，延长了其半衰期，并间接提高了其免疫原性。抗原与佐剂相关，它们能够通过激活先天免疫系统诱导局部促炎反应，导致免疫细胞募集到注射部位。抗原-佐剂复合物通过病原体相关分子模式（PAMP）来激活模式识别受体（PRR）途径。这导致先天免疫细胞的激活，产生细胞因子和趋化因子。目前，欧洲药品管理局和美国食品药品监督管理局（FDA）批准的绝大多数人类使用的疫苗都使用铝盐作为佐剂，这是疫苗配方中使用最古老的佐剂。为了提高疫苗的安全性和有效性，增加新佐剂的种类和数量是非常必要的。纳米技术和分子生物学等现代技术的进步有力地促进了对佐剂成分的开发过程，从而提高了疫苗的效力。一种好的佐剂必须是安全的、有效的、易于生产的；具有良好的药用特性（pH值、渗透压、内毒素水平等）和耐用性；最后，在经济上也可承受。微粒、乳液以及免疫刺激剂在疫苗生产中显现出巨大的潜力。递送系统佐剂佐剂可以根据不同的标准进行分类，例如它们的物理化学性质、来源和作用机制。最受关注的分类系统之一是基于其作用机制，将其分为两大类:递送系统佐剂和免疫增强佐剂。铝盐铝盐的佐剂特性是在20世纪20年代发现的，自1926年以来，这些化合物一直被用作疫苗佐剂。作为使用时间最长、疫苗中使用频率最高的佐剂，目前获得许可的疫苗中约有三分之一含有铝佐剂。在疫苗中，铝以结晶氢氧化铝（AlH）或无定形羟基磷酸铝（AlP）的复合聚合物的形式存在，形成聚集的纳米颗粒。AlH具有针状纳米颗粒的外观，而在透射电子显微镜下观察时，AlP呈现为网状。这两种铝佐剂形式通常都溶解在柠檬酸盐中，但AlP比AlH更可溶。抗原通过静电相互作用和配体交换吸附在佐剂颗粒表面。铝盐/抗原结合增强抗原呈递细胞（APC）的抗原摄取和呈递。此外，铝盐刺激NLRP3炎症小体的激活，导致IL-1β和IL-18的产生，从而引起局部炎症和APC的募集。许多疫苗使用铝佐剂，例如针对白喉和破伤风、百日咳、乙型肝炎以及肺炎球菌和脑膜炎球菌的疫苗。在欧洲，《欧洲药典》将疫苗中的铝含量设定为每剂最多1.25 mg。在美国，《美国联邦法规》将生物产品（包括疫苗）中的铝含量设定为0.85mg/剂。与食品中主要以可溶性柠檬酸盐或氯化物盐形式存在的铝不同，用作佐剂的无机铝化合物的可溶性较差；这是它们辅助作用模式的一部分。因此，由于这种在生理pH下较差的溶解性，肌肉内或皮下注射后疫苗中所含铝的吸收率将非常缓慢。一些研究评估了肌肉注射后铝的动力学。一项实验研究了基于肌内注射用26Al标记的AlH和AlP，铝的总剂量为0.85 mg。结果显示，在实验的28天内，AlH和AlP的吸收率分别为17%和51%。26Al的最大血清浓度（Cmax）为2μg/L。此外，铝的神经毒性已经在体外、离体和动物模型和人类体内进行了研究。对细菌进行的一些体外研究显示没有致突变性。而一些体内研究结果往往不一致和互相矛盾，可能存在方法上的缺陷。因此，迄今为止，尽管铝盐或多或少地产生强烈的氧化应激，但仍无法确定用作佐剂的铝盐（按推荐剂量）是否会产生毒性作用。弗氏佐剂弗氏佐剂包括完全和不完全的弗氏佐剂。这两种佐剂都是油包水乳液，能够携带抗原并刺激先天免疫系统。完全弗氏佐剂（CFA）在其结构中包括热杀死的分枝杆菌，其增强免疫反应的刺激。然而，CFA能够诱导强烈、持久的局部炎症，这可能会带来显著的疼痛，并可能在注射部位出现溃疡。不完全弗氏佐剂（IFA）不含分枝杆菌，在20世纪50年代被用作人类流感疫苗的佐剂；与没有佐剂的相同疫苗相比，它可以诱导更强、持久的抗体反应。IFA的佐剂活性是基于其作为油性抗原沉积物的特征，抗原在注射部位从中连续释放。这同时导致抗原半衰期的增加，以及通过吞噬作用、白细胞募集和浸润以及细胞因子产生强烈的局部先天免疫刺激。然而，IFA在人类疫苗配方中的常规使用引发强烈的副作用。世界卫生组织2005年进行的一项调查显示，约100万IFA受试者的免疫接种有40000名接种者出现严重副作用（如无菌脓肿）。MF59MF59是一种油包水乳液，由角鲨烯、Span 85和Tween 80在pH 6.5的10mM柠檬酸钠缓冲液中组成，平均粒径约为165nm。这是1997年意大利批准用于人类疫苗的第一种水包油乳液。目前，它被用于三价和四价（TIV和QIV）流感疫苗Fluad（Seqirus）中。研究表明，MF59的存在提高了流感疫苗在2岁以下儿童中的有效性。MF59也被用做HBV疫苗的佐剂，能够引发强烈的免疫反应，比铝诱导的免疫反应更好。关于作用机制，MF59具有与铝盐类似的效果。注射部位的贮库活性可以忽略不计，研究表明其半衰期为42小时。相反，MF59具有诱导细胞和体液免疫反应的强大能力，包括产生高滴度的功能性抗体。MF59的存在刺激局部先天免疫细胞分泌趋化因子，如CCL4、CCL2、CCL5和CXCL8，进而通过触发适应性免疫反应来驱动白细胞募集、抗原摄取并迁移到淋巴结。MF59安全且耐受性良好的，在超过35个国家已接种数百万剂。AS03AS03是一种水包油佐剂乳液，由表面活性剂聚山梨醇酯80和两种可生物降解的油组成，即在磷酸盐缓冲液中的角鲨烯和DL-α-生育酚。这种佐剂已用于流感疫苗，引发类似于MF59的免疫反应，也用于疟疾疫苗。欧盟于2009年批准销售AS03佐剂疫苗Pandemrix，而AS03佐剂甲型流感（H5N1）单价疫苗于2013年获得FDA的批准。与MF59相比，α-生育酚的抗氧化和免疫刺激特性似乎更强。此外，研究表明，AS03能够通过激活NF-κB来刺激免疫系统，从而诱导肌肉和淋巴结中的细胞因子和趋化因子分泌，并促进先天免疫细胞的迁移。AS03还可以刺激CD4+T细胞特异性免疫反应，这可以导致持久的中和抗体产生和更高水平的记忆B细胞。AS02在AS03的基础上进一步补充了两种强大的免疫刺激剂，QS-21（一种从黄芪中提取的皂苷）和3-O-去酰基-4′-单磷酸脂质a（MPL），以增强其免疫原性。病毒样颗粒病毒样颗粒（VLP）是由自组装衣壳蛋白的外壳组成的二十面体或杆状纳米颗粒（Å20–200 nm）；其已被长期研究用于疫苗开发。它们是非传染性颗粒，不包括任何遗传物质。VLP是是由具有重复表位的外部病毒外壳形成的，这些表位会立即被免疫系统识别为非自身，从而产生强大的免疫反应。除了这些重复的结构基序外，VLP的大小与病毒相似（通常在20–800 nm之间），并经过快速有效的处理，即使在没有佐剂的情况下，也能产生快速持久的免疫反应。目前，有两种重要的疫苗使用病毒样颗粒佐剂诱导免疫：乙型肝炎和乳头瘤病毒（HPV）疫苗。目前使用的乙型肝炎疫苗是一种含有乙型肝炎表面抗原（HBsAg）的重组DNA疫苗，其形式为VLP，用于预防乙型肝炎感染，该疫苗接种于15岁以下的婴儿、儿童和青少年，或感染乙型肝炎的高危人群，在乙型肝炎携带者母亲出生的新生儿中也显示出良好的免疫原性（95-99%的有效性）。HPV疫苗也是基于VLP平台的疫苗。目前的九价HPV疫苗可预防九种不同的病毒基因型，这九种病毒基因型可导致90%的宫颈癌和80-95%的肛门生殖器癌。九价HPV疫苗含有九种不同基因型HPV（6、11、16、18、31、45、53、58）的L1蛋白，形成VLP，并通过重组DNA技术合成。病毒体病毒体是一种与天然病毒结构非常相似的疫苗平台。从结构上讲，它们是由缺乏病毒遗传物质的血凝素（HA）、神经氨酸酶（NA）和磷脂（磷脂酰乙醇胺和磷脂酰胆碱）组成的重组流感病毒包膜形成的VLP。病毒体首次用于制造流感疫苗是在1975年，流感病毒是一种适用于所有年龄组的佐剂流感疫苗，对健康和免疫功能低下的儿童、成人和老年人都有良好的疗效。它能够诱导B细胞反应并产生特异性抗体。病毒体保留了病毒HA的受体结合能力和膜融合活性，但由于缺乏病毒RNA，它们在结合后无法在细胞中诱导感染。病毒体是一个完美的递送系统，能够将抗原转移到抗原呈递细胞的胞质中，并诱导细胞毒性T淋巴细胞（CTL）反应。然而，由于其弱佐剂特性，病毒体在激活APC和促进交叉呈递方面不是很有效。这种内在的限制可以通过添加更强的佐剂来消除。如最近开发了一种基于病毒体的新型流感疫苗，该病毒体补充有Toll样受体4（TLR4）配体单磷酰脂质a（MPLA）和吸附到膜中的金属离子螯合脂质DOGS NTA-Ni。用了这些MPLA佐剂的病毒体对小鼠进行体内免疫可以诱导特异性CTL。病毒体递送系统佐剂的显著优点是它们能够通过疏水性脂质相互作用将抗原吸附到其表面和管腔上。将抗原吸附到病毒体的流体磷脂双层表面会刺激与宿主细胞受体的相互作用。FDA已批准病毒体作为人类使用的纳米载体，它们具有非常高的耐受性和安全性。与亚单位疫苗对病毒入侵反应不佳相反，病毒体能够以与自然感染和其他强效佐剂非常相似的方式诱导强大的体液和细胞免疫。迄今为止，除了上述两种针对流感和甲型肝炎的基于病毒体的疫苗外，还有几种基于病毒体疫苗正在研究中，包括针对艾滋病病毒、人乳头瘤病毒、呼吸道合胞病毒和疟疾的疫苗。免疫增强剂佐剂TLR1/2激动剂在TLR1/2激动剂中，L-pampo是一种强效佐剂系统，由Pam3Csk4（Pam3）和聚肌苷酸：聚胞苷酸（polyI:C）组成。在一项研究中，L-pampo诱导了比铝佐剂更强的抗HBV抗体的产生，还涉及细胞介导的免疫反应，如增加的多功能CD4+T细胞。此外，细菌脂蛋白是TLR2识别的最有效的配体。研究表明，源自细菌脂蛋白的合成脂肽是B细胞和巨噬细胞的强激活剂，可用作疫苗佐剂。来自发酵支原体的巨噬细胞活化脂蛋白-2（MALP-2）显示通过TLR2-和MyD88依赖性信号通路激活免疫细胞。除了MALP-2外，Pam2CSK4和Pam3CSK4也是公认的TLR2激动剂，它们已被评估为对抗传染性疾病如利什曼原虫、疟疾和流感的治疗药物。TLR3激动剂TLR3是一种检测病毒dsRNA的内涵体受体，它识别poly（I:C），因为它在结构上模拟病毒RNA，从而诱导I型IFN和III型IFN的产生，并引发Th1细胞因子反应。TLR3-poly（I:C）相互作用后产生的I型IFN对于传统树突状细胞（cDC）有效激活CD8+T细胞反应特别重要。此外，poly（I:C）产生的I型IFN刺激T细胞的克隆扩增，增加效应T细胞比率和抗原特异性B细胞的数量。poly（I:C）作为一种潜在的佐剂已被广泛研究。然而，poly（I:C）对人体有毒性作用。因此，科学家的注意力集中在poly（I:C）的衍生物上，如poly（ICLC）和poly（IC12U），以及其他合成的TLR3激动剂，如ARNAX、IPH3102和RGC100。迄今为止，一些研究已经使用poly（ICLC）作为传染病的候选疫苗，如恶性疟原虫和HIV，以及癌症。研究表明，与LPS和CpG等其他TLR激动剂相比，poly（ICLC）能够引发更强的Th1免疫反应。一种新的具有佐剂潜力的TLR3激动剂是ARNAX，这是一种TLR3特异性配体，其毒性比poly（I:C）低。ARNAX研究的最重要的两个领域是癌症免疫疗法和流感疫苗。TLR4激动剂作为疫苗佐剂研究的TLR4激动剂包括AS01、AS02和AS04，它们都含有内体TLR4的配体MPLA。AS01已被用于开发针对疟疾、艾滋病毒和结核病的疫苗。AS01是一种联合佐剂系统，由两种不同的免疫刺激分子MPLA和QS-21组成，包裹在脂质体结构中。这两种化合物使用脂质体作为载体，通过胆固醇依赖性内吞作用到达细胞内。在细胞内，QS-21引起溶酶体不稳定，并促进蛋白激酶SYK的激活。MPLA作用于内涵体TLR4，诱导TRIF依赖性信号通路。AS01激活胱天蛋白酶-1，从而促进NLRP3炎症小体的激活以及IL-1β和IL-18从APC的释放。IL-18的释放导致IFN-γ的快速产生，尤其是淋巴结中的自然杀伤细胞，从而促进DC的成熟和Th1型免疫反应的诱导。TLR5激动剂TLR5是一种识别细菌鞭毛蛋白的受体，由几种免疫细胞表达。与配体的连接导致炎症途径的激活和许多炎症介质的释放，如TNF-α、IL-1β、IL-6和一氧化氮。此外，鞭毛蛋白能够引起Th1和Th2反应，而不像其他TLR配体，它们只能诱导Th1反应。鞭毛蛋白通过激活NLRC4炎症小体诱导IL-1β的产生和释放。迄今为止，至少有三种使用鞭毛蛋白作为佐剂的疫苗处于临床试验阶段：两种针对流感病毒，一种针对鼠疫耶尔森菌。TLR7/8激动剂一些研究表明，TLR7/8的激动剂能够强烈诱导Th1免疫反应。配体与TLR7/8结合能够产生高水平的I型IFN、IL-12、TNF-α和IL-1β。此外，TLR7/8和TLR9激动剂是唯一能够激活和促进cDC和浆细胞样树突状细胞（pDC）克隆扩增的激动剂分子，还能够动员CD14+CD16+炎性单核细胞和CD14dimCD16+巡逻单核细胞。最具代表性的TLR7/8激动剂是一些合成的小分子，如咪喹莫特（R837）和雷基莫特（R848），属于咪唑喹啉类。咪喹莫特目前已被批准用于治疗生殖器疣、浅表基底细胞癌和光化性角化病，而雷喹莫特已被研究用于抗病毒和抗癌治疗。然而，这些小分子具有一些内在的局限性。特别是，它们可以远离给药部位扩散，从而远离抗原，导致疗效降低并诱导全身副作用。已经表明，这些分子与铝佐剂的直接结合能够提高疫苗的效力。此外，与合成聚合物支架、脂质聚合物两亲物、聚乙二醇（PEG）、纳米凝胶、明矾和各种其他合成聚合物的结合显著增加了咪唑喹啉的递送，并改善了DC和抗原特异性T细胞的成熟。此外，先前使用咪唑喹啉与一种或多种其他TLR激动剂（如MPLA和MPLA+CpG ODN）的研究表明，这种组合增加了先天免疫反应，显著产生了抗原特异性中和抗体，并改善了Th1反应。所有这些创新都突出了TLR7/8激动剂作为候选佐剂的卓越潜力。TLR9激动剂TLR9自然识别由非甲基化胞嘧啶磷酸鸟嘌呤（CpG）二核苷酸代表的细菌DNA基序，通过MyD88依赖性途径驱动先天免疫系统的激活。CpG-ODNs在NK细胞、B细胞和pDC中引起强大的趋化因子、细胞因子和抗体产生，从而驱动强烈的Th1型免疫反应。到目前为止，已经开发出三类（A-C）不同类别的CpG-ODN，但只有B类的分子在临床试验中用作佐剂。B型CpG-ODN可以诱导pDCs的成熟，并直接与B细胞相互作用，以增强抗体的产生。最近获得许可的CpG 1018是一种具有高化学稳定性，并能够引发Th1型免疫反应佐剂能力的寡核苷酸，被用作乙型肝炎疫苗Heplisav-B的佐剂。Heplisav-B中的CpG 1018提高了疫苗的效力，与需要三剂才能获得最佳保护的传统乙型肝炎疫苗相比，只需要两剂疫苗。另一种CpG-ODN，CpG 7909，也在临床评估中，并在HBV和疟疾疫苗接种中显示出令人鼓舞的结果。此外，其他下一代TLR9激动剂也在开发中。MGN1703，是一种小的DNA分子，包括CG基序，但在结构上与CPG-ODN不同。MGN1703由一段反向互补DNA组成，该DNA在中间是双链的，两头的单链环包括三个非甲基化CG基序，形成哑铃形结构。MGN1703已被测试用作癌症疫苗的佐剂，发现它能够激活先天和适应性免疫反应，仅产生轻微或暂时的副作用。小结疫苗接种一直是且将继续是人类抗击传染病的最有力武器之一。由于这些有效和安全的预防工具，人类得以从世界许多地区铲除人类历史上最可怕的敌人。最近的新冠肺炎大流行充分强调了疫苗接种的重要性，疫苗研究必须取得进一步进展，为未来可能得传染病大流行做好准备。疫苗的效力取决于佐剂的基本特性和作用。关于疫苗接种的未来，必须更多地关注这些分子，以生产出越来越安全有效的疫苗，造福人类。参考文献：1. An Overview of Vaccine Adjuvants: Current Evidence and Future Perspectives. Vaccines (Basel).2022 May 22;10(5):819ENDIVC2024第四届核酸疫苗与创新型疫苗论坛招商热线：李欣欣 158 0045 2389戳这里，阅读原文立即领取免费参会入场券

疫苗

2024-02-13

·PRNewswire

Half year reported NPATA US$2 billion¹,² Up 13% at constant currency³

Strong CSL Behring portfolio growth especially Ig FINANCIAL HIGHLIGHTS 4 Revenue $8.05 billion, up 11% at CC3 NPAT $1.90 billion1, up 17% NPAT $1.94 billion1 at CC3, up 20% NPATA $2.02 billion1,2 , up 11% NPATA $2.06 billion1,2 at CC3, up 13% NPATA1,2 earnings per share $4.182, up 11% NPATA1,2 earnings per share $4.26 at CC3 up 13% Interim dividend 5 of US$1.19 per share Converted to Australian currency, the interim dividend is approximately A$1.81 per share, up 12% Guidance reaffirmed – FY24 NPATA2,4 anticipated to be in the range of approximately $2.9 billion to $3.0 billion2 at CC3 MELBOURNE, Australia, Feb. 13, 2024 /PRNewswire/ -- CSL Limited (ASX:CSL; USOTC:CSLLY) today announces a reported net profit after tax of $1.90 billion1 for the 6 months ended 31 December 2023, up 20% on a constant currency basis3. Underlying profit (NPATA) was $2.02 billion1,2, up 13% on a constant currency basis to $2.06 billion1,2,3. Dr. Paul McKenzie, CSL's Chief Executive Officer and Managing Director said, "Our strong first-half result for the 2024 financial year was driven by CSL Behring's exceptional performance across its portfolio, especially immunoglobulins. The plasma initiatives we have implemented are starting to drive gross margin recovery. "CSL Seqirus achieved solid growth in a challenging season. Its portfolio of differentiated products outperformed the market. "For CSL Vifor we are well prepared for the transitioning iron market." PERFORMANCE CSL Behring Total revenue was $5,238 million, up 14%3 when compared to the prior comparable period. Immunoglobulin (Ig) product sales of $2,757 million, increased 23%3 with strong growth recorded across all geographies driven by global plasma supply and patient demand. PRIVIGEN® / INTRAGRAM® (Immune Globulin Intravenous (Human), 10% Liquid) sales grew 27%3 as the momentum from the prior year continued in improving product availability and patient diagnosis rates. HIZENTRA® (Immune Globulin Subcutaneous (Human), 20% Liquid) sales were up 18%3 driven by patient diagnosis rates. HIZENTRA® continues to be the clear market leader for subcutaneous immunoglobulin. Underlying demand for Ig continues to be strong due to significant patient needs in core indications – namely Primary Immune Deficiency, Secondary Immune Deficiency and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Albumin sales of $613 million, were up 8%3. Sales were strong in emerging markets with solid growth in the US and Europe. Growth in China was modest, tempered by competitive pressure. Haemophilia product sales of $662 million increased 8%3. IDELVION®, CSL Behring's novel long-acting recombinant factor IX product achieved growth of 7%3 and continues to be the market leader in key markets. HEMGENIX®, the first and only gene therapy for haemophilia B was successfully launched in the US in FY23 and patient referrals have been accelerating. The haemophilia A market continued to be competitive resulting in a modest decline in sales for AFSTYLA®, a novel recombinant factor VIII product. Plasma-derived haemophilia products, however, achieved growth of 8% driven by HUMATE® / HAEMATE®, therapies for the treatment of patients with von Willebrand disease. Specialty products sales of $976 million, were up 6%3 led predominately by demand for KCENTRA® and HAEGARDA®. KCENTRA® (4 factor prothrombin complex concentrate) recorded sales growth of 12%3, as it continues to further penetrate the warfarin reversal market in the US. HAEGARDA®, our therapy for patients with Hereditary Angioedema, increased 9%, driven by the continued shift from on-demand to prophylaxis treatment and a strong performance in the UK and Europe. Garadacimab (Anti-FXIIa) for HAE, was filed for regulatory approval in the US and EU. Plasma Collections Plasma collections remain strong. The cost of collections, which includes donor compensation and labour, continued to trend down. A new roll out plan for the RIKA plasmapheresis devices was developed. Deployment across the US fleet is expected over the next 18 months. In addition, results from an individualised nomogram trial conducted by our supplier have been submitted for regulatory approval. CSL Seqirus Total revenue of $1,804 million, was up 2%3 driven by the adjuvanted influenza vaccine FLUAD®, which increased by 14%3. This growth was achieved against a backdrop of reduced rates of immunisation and highlights the strength of CSL Seqirus' differentiated product portfolio. During the period: Self-amplifying mRNA vaccine for COVID was approved by Japan's Ministry of Health, Labour and Welfare aQIVc, a next generation influenza vaccine combining adjuvant technology with cell-based manufacturing, enrolled its last patient in the Phase III clinical study in January 2024. CSL Vifor Total revenue was $1,011 million. The prior comparable period included only 5 months revenue following the acquisition of Vifor Pharma in August 2022. During the period: Preparations were made for the transitioning iron market There was strong performance from the long-acting erythropoiesis-stimulating agent, MIRCERA® TAVNEOS® was successfully launched in multiple European countries While the strategic potential of the business remains strong, we have dampened our near-term growth aspirations for CSL Vifor. Expense Performance Research and development (R&D) expenses were $669 million8 , up 11%3 when compared to the prior comparable period. The increase in expenses reflects higher costs associated with the progression of the R&D portfolio and investment in R&D infrastructure. Selling and marketing expenses (S&M) were $707 million8, up 2%3 in comparison to the prior comparable period. An additional month of CSL Vifor and an increase in labour costs accounts for the increase in S&M expenses while other S&M expenses were held in line with the prior comparable period. General and administrative (G&A) expenses were $323 million8, down 7%3 due to favourable foreign exchange differences and efficiencies generated from the centralisation of the group's Enabling Functions. Depreciation and amortisation (D&A) expense (excluding acquired intellectual property) was $297 million, up 1%3. Net finance costs were $234 million9, up 32%3. The increase in net finance costs was due to the debt associated with the acquisition of Vifor Pharma and higher interest rates. Financial position Cashflow from operations was $1,069 million, up 9%. The increase was driven by higher profitability and overall growth in sales. This was partly offset by higher payments for income tax and interest. Cash outflow from investing was $702 million, down significantly when compared to the prior comparable period as payment for the acquisition of Vifor Pharma was made in the prior period. CSL's balance sheet remains in a strong position with net assets of $19,162 million. Current assets increased by 10% to $10,146 million. The main driver was an increase in receivables due to the increase in sales and the seasonality of CSL Seqirus. Non-current assets increased by 1% to $27,158 million in comparison to the previous year. Current liabilities increased by 2% to $4,718 million. The increase in interest-bearing liabilities and borrowings (bank debt) was offset by the decrease in trade and other payables and current tax liabilities. Non-current liabilities decreased by 3% to $13,424 million. The decrease was due to the reclassification of certain bank borrowings as current, coupled with repayment across the Group's debt portfolio including the private placement senior notes. Outlook (at FY23 exchange rates) Commenting on CSL's outlook, Dr. McKenzie said, "For FY24, I am pleased to reaffirm our previous guidance. CSL's underlying profit, NPATA is expected be in the range of approximately $2.9 billion to $3.0 billion at constant currency3, representing growth over FY23 of approximately 13-17%[6]" "CSL is in a strong position to deliver annualised double-digit earnings growth over the medium term. "The strong growth in our immunoglobulins franchise is expected to continue as patient demand remains strong. "We have a number of initiatives underway in plasma collections that are improving efficiencies and processing times, supporting continued expansion in CSL Behring's gross margin. "Our transformational gene therapy product for haemophilia B patients, HEMGENIX®, is attracting significant interest from patients and health care professionals and patient referrals have accelerated. We expect more patients dosed in the second half of this financial year. "CSL Seqirus has performed well in a challenging season. However, due to the seasonality of this business we anticipate it to post a loss in the second half of the fiscal year. "For CSL Vifor, we are operating within an evolving iron market. While there are challenges for near-term growth, we are well positioned for iron competition in the EU and further geographic expansion. Our focus remains on unlocking value by leveraging capabilities across the CSL group", Dr. McKenzie concluded. In compiling the company's financial forecasts for FY24, a number of key variables that may have a significant impact on guidance have been identified and these have been included in the endnote[7]. FURTHER INFORMATION Additional details about CSL's results are included in the company's 4D statement, investor presentation slides and webcast, all of which can be found on CSL's website A glossary of medical terms can also be found on the website. 1 Attributable to CSL shareholders 2 Statutory net profit after tax (NPAT) before impairment and amortisation of acquired intellectual property, business acquisition and integration costs and the unwind of the inventory fair value uplift. 3 Constant currency (CC) removes the impact of exchange rate movements, facilitating the comparability of operational performance. For further detail refer to CSL's Financial Statements for the Half Year ended December 2023 (Directors Report). 4 All figures are expressed in US dollars unless otherwise stated. 5 For shareholders with an Australian registered address, the interim dividend of US$1.19 per share (approximately A$1.81) is expected to be paid on 3 April 2024. For shareholders with a New Zealand registered address the interim dividend of US$1.19 per share (approximately NZ$1.94) is expected to be paid on 3 April 2024. The exchange rates will be fixed at the record date of 12 March 2024. All other shareholders will be paid in US$. CSL also offers shareholders the opportunity to receive dividend payments in US$ by direct credit to a US bank account. 6 % growth rates excludes the one-off gain from the sale of property in FY23 (NPATA $44m). 7 Key variables that could cause actual results to differ materially include: the success and timing of research and development activities; decisions by regulatory authorities regarding approval of our products as well as their decisions regarding label claims; competitive developments affecting our products; the ability to successfully market new and existing products; difficulties or delays in manufacturing; ability to collect plasma; trade buying patterns and fluctuations in interest and currency exchange rates; legislation or regulations that affect product production, distribution, pricing, reimbursement, access or tax; acquisitions and divestitures; research collaborations; litigation or government investigations; and CSL's ability to protect its patents and other intellectual property. 8 Underlying results are adjusted to exclude amortisation of acquired intellectual property ($132 million), business acquisition and integrations costs and the unwind of the inventory fair value uplift. 9 At reported currency For further information, please contact: Investors: Bernard Ronchi Director, Investor Relations CSL Limited P: +61 3 9389 3470 E: [email protected] Stephen McKeon Director, Investor Relations CSL Limited P: +61 402 231 696 E: [email protected] Media: Jimmy Baker Communications CSL Limited P: +61 450 909 211 E: [email protected] SOURCE CSL Limited

临床3期上市批准疫苗财报临床结果

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

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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	2015-11-24
乙型流感病毒感染	美国	Seqirus GmbH	2015-11-24

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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3期	美国	Novartis Vaccines & Diagnostics SL	2007-10-01
流感病毒感染	临床3期	芬兰	Novartis Vaccines & Diagnostics SL	2007-10-01
流感病毒感染	临床3期	波兰	Novartis Vaccines & Diagnostics SL	2007-10-01

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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


NCT05007041 (CTgov)	临床4期	带状疱疹 \| 药物不良反应 \| 流感病毒感染 ... 更多	267	Zoster Vaccine Recombinant (RZV) (Zoster Vaccine Recombinant (RZV) and Quadrivalent Adjuvanted Influenza Vaccine)	淵選鬱範醖繭艱鹹繭醖(衊鹽窪淵獵醖觸壓艱齋): Difference in proportions = -0.96 (95.0% CI, -8.94 ~ 7.1), P-Value = 0.0037 更多	-	2024-05-01
				Zoster Vaccine Recombinant (RZV) (Zoster Vaccine Recombinant (RZV) and High-dose Quadrivalent Influenza Vaccine)
NCT03694808 (CTgov)	临床4期	流感病毒感染	478	Fluad Vaccine (Fluad Vaccine)	觸壓範繭鑰願醖淵築鹹(積壓糧廠窪艱鏇憲壓醖) = 襯壓構遞願顧鹹淵窪醖膚鹹鹹窪製憲蓋範遞顧 (鬱蓋窪夢獵衊積鬱窪遞, 鬱遞夢夢夢壓窪齋衊艱 ~ 願觸餘衊築構膚鹽醖襯) 更多	-	2024-04-30
				Fluzone HD Vaccine (Fluzone Vaccine)	觸壓範繭鑰願醖淵築鹹(積壓糧廠窪艱鏇憲壓醖) = 鹽簾鹹獵遞襯範築範鬱膚鹹鹹窪製憲蓋範遞顧 (鬱蓋窪夢獵衊積鬱窪遞, 壓製糧壓壓鏇構襯觸願 ~ 衊鹽繭壓蓋繭獵獵構鏇) 更多
NCT03603509 (CTgov)	临床4期	流感病毒感染	241	Fluad Vaccine (Fluad Vaccine)	淵製積醖觸製襯窪鹽築(糧製鹹鑰構簾積簾鹹積) = 鑰簾糧選選遞積鹹壓鑰獵獵製構齋顧構壓衊憲 (憲願夢範齋選壓遞餘鏇, 範顧蓋淵淵鹹衊構遞艱 ~ 鹽艱鹹鏇積夢糧衊襯衊) 更多	-	2023-05-16
				Fluzone High-Dose (Fluzone Vaccine)	淵製積醖觸製襯窪鹽築(糧製鹹鑰構簾積簾鹹積) = 壓艱壓蓋艱膚鬱遞夢壓獵獵製構齋顧構壓衊憲 (憲願夢範齋選壓遞餘鏇, 簾憲壓憲構網顧鬱積構 ~ 艱蓋餘憲積簾鬱範鹽糧) 更多
NCT04077424 (single cell, CTgov)	临床4期	流感病毒感染	10	Fluzone-High Dose Quadrivalent (Fluzone-High Dose)	願窪顧糧糧網遞網艱選(淵壓淵鏇遞艱鬱觸鏇網) = 壓鏇鑰蓋鹹願膚鹹廠憲淵蓋鬱蓋衊製淵膚網範 (夢構餘壓繭築鏇選蓋夢, 鬱顧觸構簾淵遞構獵襯 ~ 簾廠觸鹽繭壓夢醖構艱) 更多	-	2022-07-12
				Fluad (Fluad)	願窪顧糧糧網遞網艱選(淵壓淵鏇遞艱鬱觸鏇網) = 蓋製窪範範願遞構衊艱淵蓋鬱蓋衊製淵膚網範 (夢構餘壓繭築鏇選蓋夢, 範糧遞築膚觸壓齋壓淵 ~ 蓋鹽襯構顧艱廠廠鹹衊) 更多
NCT03183908 (CTgov)	临床4期	流感病毒感染 \| 药物不良反应 \| 注射部位反应 ... 更多	757	FLUAD® (Adjuvanted Influenza Vaccine (FLUAD®))	鬱鹽鬱鹹繭夢淵憲選選(憲選衊繭鬱製憲鬱選醖): Difference in proportions = -2.7 (95% CI, -5.8 ~ 0.4) 更多	-	2021-03-30
				Fluzone® High-Dose (High-dose Influenza Vaccine (Fluzone® HD))