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

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

2025-10-01·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.

2025-08-01·VACCINE

Immunogenicity and safety of quadrivalent recombinant influenza vaccine in Korean adults: Phase III, randomized study

Article

作者: Choe, Sunho ; Peng, Lin ; Choi, Won Suk ; Lee, Jacob ; Samson, Sandrine ; Shin, Sooyoun ; Kim, Woo Joo ; Ottaviano, Cecilia

Quadrivalent recombinant influenza vaccine (RIV4) is indicated for active immunization against influenza virus in adults (≥18 years) in countries where it is currently registered. This Phase III, parallel, randomized, modified double-blind, active controlled, multi-center study was designed to compare the immunogenicity and safety of single dose intramuscular RIV4 with a locally-licensed quadrivalent-inactivated influenza vaccine (IIV4, Fluarix® quadrivalent) in participants aged ≥18 years during 2021-22 Northern Hemisphere influenza season at three tertiary care centers in South Korea. Participants were randomized (1:1) to receive single dose intramuscular RIV4 or IIV4. All participants were centrally assigned to randomized study intervention using an interactive response technology (IRT). Participants, investigators, and the staff in-charge of the sampling, safety assessment and immunogenicity assays were blinded. The overall mean age of 300 participants who completed the study was 46.1 years. The post-vaccination geometric mean fold-rise of HAI antibodies were 32.0, 13.2, 6.1, and 5.3 in RIV4 group, and 22.3, 8.0, 4.7, and 3.4 in IIV4 group for the A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage strains, respectively. Seroconversion in RIV4 was comparable or higher than IIV4. Neither immediate unsolicited AEs were reported within 30 min of vaccination nor SAEs, AESIs nor deaths were reported during the 6-month follow-up. Clinical Trial Registration:ClinicalTrials.gov number - NCT05144945.

2025-08-01·AJOG global reports

Corrigendum to ‘Safety of quadrivalent recombinant influenza vaccine in pregnant persons and their infants’ [AJOG Global Reports Volume 4, Issue 4, November 2024, 100395]

作者: Talanova, Oxana ; Izikson, Ruvim ; Gandhi-Banga, Sonja ; Yee, Arnold ; Lewis, Ned ; Hsiao, Amber ; Klein, Nicola P ; Inamdar, Ajinkya ; Kabler, Heidi ; Fireman, Bruce ; Hansen, John ; Selmani, Alexandre

[This corrects the article DOI: 10.1016/j.xagr.2024.100395.].

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

2025-10-14

·EINPresswire

2025 Biological License Application Supplement Noteworthy Approvals

Whole Blood and Blood Components (Convalescent Plasma, High Titer, Anti-SARS-CoV-2 (Whole Blood-derived) Treatment of COVID-19 in patients with immunosuppressive disease or receiving immunosuppressive treatment. 125396/21 Stanford Blood Center 3373 Hillview Avenue Palo Alto, CA 94304 10/10/2025 VYJUVEK beremagene geperpavec-svdt Expand the indication to treat wounds in adults and pediatric patients (0 to 16 years of age) with dystrophic epidermolysis bullosa, and to allow application of VYJUVEK in home setting by a healthcare professional, patient or caregiver. 125774/89 Krystal Biotech, Inc. 2100 Wharton Street Suite 701 Pittsburgh, PA 15203 Lic. # 2301 9/12/2025 VONVENDI von Willebrand Factor (Recombinant) To expand the current approved adult prophylaxis indication for type 3 von Willebrand disease (VWD) to include adults with type 1 and type 2 VWD and to expand the use to pediatric patients with VWD for on demand treatment and control of bleeding episodes and perioperative management of bleeding. 125577/691 Takeda Pharmaceuticals USA, Inc 500 Kendall Street Cambridge, MA 02142 Lic. # 1898 9/5/2025 NUVAXOVID COVID-19 Vaccine, Adjuvanted To include the 2025-2026 Formula and associated labeling revisions. 125817/6 Novavax, Inc. 700 Quince Orchard Road Gaithersburg, MD 20878 Lic. # 2349 8/27/2025 MNEXSPIKE COVID-19 Vaccine, mRNA To include the 2025-2026 Formula and associated labeling revisions for use in individuals who are 65 years of age and older, or 12 years through 64 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19. 125835/6 ModernaTX, Inc. 325 Binney Street Cambridge, MA 02142 Lic. # 2256 8/27/2025 SPIKEVAX COVID-19 Vaccine, mRNA To include the 2025-2026 Formula and associated labeling revisions. 125752/305 Moderna TX, Inc. 325 Binney Street Cambridge, MA 02142 Lic. # 2256 8/27/2025 COMIRNATY COVID-19 Vaccine, mRNA To include: 10 mcg drug product (2025-2026 Formula) in the single-dose vial presentation manufactured at the Pfizer, Puurs facility and associated labeling revisions, for use in individuals 5 years through 11 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19; and 30 mcg drug product (2025-2026 Formula) in the single-dose prefilled syringe presentation manufactured at the Pfizer, Puurs facility and associated labeling revisions, for use in individuals who are 65 years of age and older, or 12 years through 64 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19. 125742/656 BioNTech Manufacturing GmbH Pfizer, Inc. 66 Hudson Boulevard East New York, NY 10001 Lic. # 2229 8/27/2025 AREXVY Respiratory Syncytial Virus Vaccine, Adjuvanted To include data on the safety and efficacy of AREXVY against Respiratory Syncytial Virus (RSV) associated lower respiratory tract disease in individuals 60 years of age and older over three RSV seasons following administration of a single dose. 125775/297 GlaxoSmithKline Biologicals 14200 Shady Grove Road VR1500 Rockville, MD 20850-7464 Lic. # 1617 8/8/2025 CAPVAXIVE Pneumococcal 21-valent Conjugate Vaccine To update Section 8 "Use in Specific Populations", Section 6 “Clinical Trials Experience”, and Section 14 “Clinical Studies” of the package insert for the inclusion of individuals living with HIV (V116-007) and individuals at increased risk of pneumococcal disease (V116-008). 125814/149 Merck Sharp & Dohme LLC P.O. Box 1000 UG2D-68 North Wales, PA 19454-2505 Lic. # 0002 7/31/2025 Imovax Rabies Rabies Vaccine To update the package insert to include a 2-dose pre-exposure prophylaxis dosing regimen in addition to the currently approved 3-dose regimen. 103931/5342 Sanofi Pasteur SA Discovery Drive Swiftwater, PA 18370-0187 Lic. # 1724 7/24/2025 SPIKEVAX COVID-19 Vaccine To prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals who are 65 years of age and older, or 6 months through 64 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19, and to include a new 0.25 mL pre-filled syringe presentation. 125752/276 ModernaTX, Inc. 325 Binney Street Cambridge, MA 02142 Lic. # 2256 7/9/2025 GAMMAGARD LIQUID ERC Immune globulin infusion (human) 10% solution For the indication of a replacement therapy for primary humoral immunodeficiency (PI) in adult and pediatric patients two years of age and older. 125105/2184 Takeda Pharmaceuticals U.S.A., Inc. 650 E. Kendall Street Cambridge, MA 02142 Lic. # 1898 6/27/2025 MRESVIA Respiratory Syncytial Virus Vaccine To revise the indication and usage to include active immunization for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in individuals 18 through 59 years of age who are at increased risk for LRTD caused by RSV. 125796/37 ModernaTX, Inc. 325 Binney Street Cambridge, MA 02142 Lic. # 2256 6/12/2025 ABRYSVO Respiratory Syncytial Virus Vaccine To update the Package Insert to include safety and efficacy data from two full Respiratory Syncytial Virus (RSV) seasons from the Phase 3 clinical study C3671013, and the final safety data from the Phase 3 study C3671008. 125769/277 Pfizer Inc. 500 Arcola Road Collegeville, PA 19426 Lic. # 2001 6/9/2025 MenQuadfi Meningococcal (Groups A, C, Y, W) Conjugate Vaccine To update the Package Insert to include safety and effectiveness data from postmarketing requirement (PMR) studies MET41, MET42 and MET61 that support lowering the age for use to include individuals 6 weeks through 23 months of age. 125701/262 Sanofi Pasteur, Inc. Discovery Drive Swiftwater, PA 18370-0187 Lic. # 1725 5/23/2025 AREXVY Respiratory Syncytial Virus Vaccine, Adjuvanted To update the Package Insert to include data from two clinical studies of concomitant administration of AREXVY with influenza vaccines in individuals 65 years of age and older. 125775/247 GlaxoSmithKline Biologicals 14200 Shady Grove Road Rockville, MD 20850-7464 Lic. # 1617 5/23/2025 Jivi Antihemophilic Factor (recombinant), PEGylated-aucl To revise the indication to include pediatric patients 7 to <12 years of age. 125661/972 Bayer HealthCare LLC 100 Bayer Boulevard, P.O. Box 915 Whippany, NJ 07981-0915 Lic. # 0008 5/14/2025 FluBlok Influenza Vaccine To update the product labeling to include data and results from PREA PMR studies VAP00026 (3-8 year olds) and VAP00027 (9-17 and 18-49 year olds), and to use data from VAP00027 to support extending the Flublok indication to individuals 9 through 17 years of age, and to fulfill (PREA) PMR #1 and (PREA) PMR #2 (125285/471). 125285/613 Protein Sciences Corporation Sanofi Pasteur Inc. Discovery Drive Swiftwater, PA 18370 Lic. #1795 03/31/2025 JYNNEOS Smallpox and Mpox Vaccine, Live, Non-replicating To include a two-vial presentation of JYNNEOS that consists of a Lyophilized Antigen Component vial and a Diluent Component vial. 125678/119 Bavarian Nordic A/S Bavarian Nordic Inc. 1005 Slater Road, Suite 101 Durham, NC 27703 Lic. #2096 03/31/2025 SHINGRIX Zoster Vaccine Recombinant, Adjuvanted To update the US Prescribing Information to include information from Study Zoster-049 on long term effectiveness of SHINGRIX. 125614/1022 GlaxoSmithKline Biologicals 14200 Shady Grove Road Rockville, MD 20850-7464 Lic. #1617 03/21/2025 ODACTRA House Dust Mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus) Allergen Extract To include use in children 5 through 11 years of age. 125592/218 ALK-Abello A/S ALK-Abello Inc. 135 Route 202/206 Suite 16 Bedminster, NJ 07921 Lic. #1292 02/27/2025 Anti-Human Globulin To replace the Anti-C3d used in MTS Anti-IgG, -C3d gel cards manufactured in Pompano Beach, Florida facility. 103461/5123 Micro Typing Systems, Inc. 100 Indigo Creek Drive Rochester, NY 14626 Lic. #1177 01/28/2025 Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

疫苗临床3期上市批准免疫疗法临床结果

2025-10-10

·Pharmaceutical Technology

Flu vaccine uptake increases 28% in England

There are currently seven licensed flu vaccines available for the 2025 to 2026 season. Tong_stocker via Shutterstock.com. The number of people receiving a flu vaccine across England has increased by over a quarter, as cases of both influenza and Covid-19 start to climb at the start of the viral season. Data from England’s National Health Service (NHS) shows that the flu jab has been administered to 4.3 million people, a 28% rise from 3.36 million who received the vaccine at the same point last year. The vaccination drive comes as the flu season commences. Influenza infections start to uptick around October, with peaks usually coming in December. Vaccines can help protect against the flu and are offered to people every year at higher risk of becoming seriously ill. Caused by the influenza virus, flu is significantly more serious than the common cold, which is caused by a wide range of viruses. The UK Health Security Agency’s (UKHSA’s) latest surveillance data showed that flu positivity increased from 1.9% to 3.3% and Covid-19 positivity in hospital settings increased from 11.7% in the previous week to 12.9%. One of the key changes to this year’s vaccine programme is the switch from quadrivalent (QIV) to trivalent (TIV) vaccines in inactivated influenza vaccines (IIV). The World Health Organization (WHO) recommends the composition of influenza vaccine strains each year based on global virus trends. For the 2025/26 season, WHO recommends the use of the trivalent vaccine for the Northern Hemisphere. This is because the influenza B/Yamagata lineage virus has not been detected worldwide since 2020 and is not predicted to cause future epidemics. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence There are currently seven licensed flu vaccines available for the 2025 to 2026 season. CSL Seqirus’ cell-based quadrivalent influenza vaccine, Sanofi’s Vaxigrip, and Viatris’ Influenza vaccine TIV MYL are given to those above six months of age. AstraZeneca’s Fluenz Tetra, a live attenuated influenza vaccine (LAIV), is for those between two and 18 years of age. For adults over 18 years of age, Sanofi’s Supemtek, a recombinant trivalent influenza vaccine, is used. CSL Seqirus’ other adjuvanted trivalent influenza vaccine is licensed for use for adults above 50 years of age. Sanofi’s Efluelda TIV-HD is available to those 60 years of age and over. The NHS offers flu vaccines for everyone aged 65 and over, and for adults 18 to 64 years of age in certain risk groups. The NHS is bracing itself for a busy winter. Regional teams are improving access to the vaccines through mobile vaccination buses, family community drop-in sessions, and, in an NHS first, delivering flu vaccines to two and three-year-olds in community pharmacies. Meanwhile, eligibility for the Covid-19 vaccine changed for this autumn and winter following an update on recommendations by the Joint Committee on Vaccination and Immunisation (JCVI). The committee advises that the vaccines be offered to people aged 75 or over, residents in care homes, or anyone with a weakened immune system. Dr Amanda Doyle, national director for Primary Care and Community Services at NHS England, said : “Vaccination is a crucial part of our efforts to protect the vulnerable and prepare for what we expect to be a very challenging winter, so I’m delighted to see this big increase in the numbers of people getting vaccinated at this stage. “Vaccinations are our best defence against these potentially very dangerous viruses and can genuinely save lives.” Pharmaceutical Technology Excellence Awards - The Benefits of Entering Gain the recognition you deserve! The Pharmaceutical Technology Excellence Awards celebrate innovation, leadership, and impact. By entering, you showcase your achievements, elevate your industry profile, and position yourself among top leaders driving pharmaceutical advancements. Don’t miss your chance to stand out—submit your entry today! Nominate Now

疫苗上市批准

2025-08-18

·生物制品圈

流感病毒总在 “变脸”？这些新技术让疫苗学会 “认本质”

摘要：流感是威胁全球公共健康的 “常客”，世界卫生组织数据显示，它每年导致 300 万至 500 万重症病例，29 万至 65 万例呼吸道相关死亡。现有流感疫苗虽能提供一定保护，但因病毒的抗原漂移和抗原转换等 “逃避免疫” 机制，需年年更新且对大流行株保护有限。本文将从流感病毒的 “生存智慧” 说起，详解现有疫苗的局限性，再聚焦科学家为开发 “进化抗性” 流感疫苗（即通用流感疫苗）所做的努力 —— 包括靶向病毒保守区域、优化疫苗设计策略、升级递送技术等，带读者了解这场与病毒进化赛跑的科学突破。一、流感病毒：自然界的 “伪装大师”1.1 每年 “变脸” 的病毒：抗原漂移与抗原转换流感病毒之所以让人防不胜防，核心在于它的 “进化魔法”。我们可以把病毒想象成一个不断换衣服的小偷：每年换件 “小外套”（抗原漂移），偶尔直接换身 “新造型”（抗原转换），让人体免疫系统难以识别。抗原漂移是病毒的 “日常操作”。流感病毒的遗传物质是 RNA，复制时依赖一种 “不纠错” 的酶（RNA 依赖的 RNA 聚合酶），这导致它很容易出现基因突变。这些突变会一点点改变病毒表面的血凝素（HA）和神经氨酸酶（NA）—— 这两种糖蛋白就像病毒的 “身份证”，是疫苗诱导抗体的主要目标。当突变积累到一定程度，人体之前产生的抗体就认不出它们了，这就是为什么每年的流感疫苗都可能 “失效”。比如 2016-2017 赛季，H3N2 亚型病毒在鸡蛋中培养时发生蛋适应性突变，导致疫苗株与流行株 “长相不符”，保护效果大幅下降。抗原转换则是病毒的 “大招”，可能引发大流行。当两种不同流感病毒（比如人流感和禽流感）同时感染同一宿主（如猪），它们的基因片段会像 “洗牌” 一样重组，产生全新的 HA 或 NA 亚型 —— 人类免疫系统对这种 “新面孔” 毫无防备。历史上的四次大流行（1918 年 H1N1 “西班牙流感”、1957 年 H2N2 “亚洲流感”、1968 年 H3N2 “香港流感”、2009 年 H1N1 “ swine flu”），都是抗原转换的 “杰作”。1.2 现有疫苗的 “软肋”：为什么年年打，还是可能中招？目前的流感疫苗主要有两种：灭活疫苗和减毒活疫苗，它们的核心思路是 “模仿” 流行株的 HA，诱导人体产生针对性抗体。但这种 “以变应变” 的策略有明显短板：匹配度是关键：如果疫苗株与当年流行株的 HA 亚型 “长得不像”（即疫苗错配），保护力会骤降。香港一项 17 年的研究发现，H3N2 和 B 型流感的疫苗株往往在东亚流行一年后才被选入疫苗，导致部署时已“过时”。受生产技术限制：多数疫苗依赖鸡蛋培养，而病毒在鸡蛋中可能发生突变（如 HA 的糖基化位点变化），进一步降低匹配度。个体差异影响大：老人、免疫低下者等高危人群的免疫反应较弱；此外，抗原印记（即首次感染的流感株会影响后续免疫反应）也会让疫苗效果打折扣。数据显示，现有疫苗的有效性（VE）每年波动在 0%-60%，对 H3N2 亚型的保护力尤其不稳定 —— 这也让科学家们意识到：必须跳出 “年年追着病毒跑” 的模式，开发能应对多种变异株的通用流感疫苗。二、瞄准病毒 “不变的软肋”：通用疫苗的设计思路理想的通用流感疫苗需满足三个标准：对甲流 Group 1（如 H1、H5）和 Group 2（如 H3、H7）的保护率≥75%，保护期至少 1 年，且适合所有年龄组。要实现这一点，关键是找到病毒身上 “不轻易变” 的部分 —— 也就是保守区域。2.1 盯住 HA 的 “茎”：病毒的 “致命骨架” HA 是流感病毒表面最显眼的蛋白，由 “头部” 和 “茎部” 组成。头部是抗原漂移的 “重灾区”，但茎部因涉及病毒入侵细胞的关键功能（如膜融合），进化非常缓慢 —— 这成了疫苗开发的 “黄金靶点”。（1）嵌合 HA 疫苗（cHA）：给病毒 “换个头” 科学家想出了一个 “障眼法”：把一种 HA 的茎部和另一种 HA 的头部 “拼接” 起来（比如 H1 的茎 + 禽流感 H5 的头）。这种嵌合 HA（cHA）能 “骗” 免疫系统把注意力集中在茎部，而非易变的头部。动物实验显示，cHA 疫苗能诱导针对 H1、H3、H5、H7 等多种亚型的抗体，还能激活CD4⁺和 CD8⁺ T 细胞（负责长期免疫记忆）。2021 年一项 I 期临床试验证实，含佐剂的 cHA 疫苗在成人中安全且能诱导强效的抗茎部抗体，为其走向临床奠定了基础。（2）无头 HA 疫苗：直接暴露 “软肋” 另一种思路更直接：干脆去掉 HA 的头部，只保留茎部。这种无头 HA 疫苗能让免疫系统 “专心” 攻击茎部的保守位点（如融合肽），诱导的抗体可中和多种流感株。研究发现，它在小鼠中能产生高滴度的茎部特异性抗体，对异源病毒（即与疫苗株不同的病毒）也有保护作用。不过，如何保证茎部蛋白的稳定性和正确折叠，仍是需要攻克的技术难题。2.2 多亚型 “联合作战”：让疫苗覆盖更广既然单个 HA 亚型容易变，那不如一次 “瞄准” 多个亚型？多价疫苗（含多种 HA 亚型）就是基于这个思路。比如同时纳入季节性 H1N1、H3N2 和禽流感 H5 的 HA，能训练免疫系统识别更多 “病毒面孔”。实验显示，含 H3 多种亚型的疫苗能诱导中和 H3 家族所有成员的抗体；而 H1、H5、H7 的重组 HA 加上佐剂后，甚至能让抗体 “跨界” 识别未包含在疫苗中的亚型。更巧妙的是，通过化学方法将不同 HA “连” 起来，还能减少抗体的 “偏见”（即只针对某一亚型），让 T 细胞更好地帮助 B 细胞产生广谱抗体 —— 这就像给免疫系统配备了 “多面手”，应对变异更从容。2.3 给疫苗 “加 buff”：佐剂的神奇作用佐剂是疫苗的 “得力助手”，能增强免疫反应、减少抗原用量，尤其适合老人、儿童等免疫力较弱的人群。传统疫苗常用铝盐（Alum），但它主要增强体液免疫（抗体反应）；新型佐剂则能 “全面升级” 免疫效果： MF59 和 AS03（油包水乳液）：能同时激活体液和细胞免疫，在 2009 年 H1N1 大流行中，含 AS03 的疫苗用 1/4 剂量就能达到普通疫苗的效果，还能快速诱导免疫反应。 Matrix-M（皂苷纳米颗粒）：在老年人群中表现突出，能增强对同源和异源病毒的交叉保护，还能减少抗原用量（即剂量节省）。 TLR 激动剂：比如 TLR3 配体（如 Poly I:C）能激活先天免疫，让免疫系统 “警觉性” 更高，诱导更强的 T 细胞反应和交叉抗体。这些佐剂不仅能提升现有疫苗的效果，更是通用疫苗的 “好搭档”—— 它们能帮助免疫系统更有效地识别病毒的保守区域，延长保护时间。2.4 不止 HA：NA 和内部蛋白的 “隐藏价值” 过去，疫苗研发主要盯着 HA，但科学家发现，神经氨酸酶（NA）和病毒内部蛋白（如基质蛋白、核蛋白）也有 “潜力”： NA：虽不如 HA 受关注，但它进化更慢，且抗体针对 NA 能抑制病毒从细胞释放（而非阻止入侵），减少病毒传播。更重要的是，HA 和 NA 的功能相互依赖（即HA-NA 平衡）—— 如果病毒通过突变 HA 逃避免疫，NA 的 “配合” 可能受限，因此同时靶向两者能降低病毒逃逸的概率。内部蛋白：如基质蛋白 M2（尤其是其胞外区 M2e）、M1和核蛋白（NP），在所有流感株中高度保守。M2e 疫苗能诱导抗体通过 “抗体依赖的细胞毒性（ADCC）” 清除感染细胞；NP 和 M1 则能激活 T 细胞，产生交叉保护（比如 2009 年 H1N1 大流行中，曾感染过类似病毒的老人因有 NP 特异性 T 细胞，症状更轻）。目前，科学家正在测试 “HA 茎部 + M2e+NA” 的多抗原疫苗，希望通过 “多靶点攻击” 让病毒难以逃逸。三、预测与设计：让疫苗 “未卜先知” 要对抗病毒的进化，不仅要瞄准保守区域，还要能 “预测” 病毒可能的变异 —— 这就需要策略性表位预测与选择技术。3.1 糖基化掩盖：给免疫系统 “指方向” 病毒会用糖基化（即给蛋白加 “糖链”）来掩盖 HA 头部的抗原位点，逃避免疫识别。科学家反其道而行之：通过人工添加糖基化位点，“遮蔽” HA 头部的易变区域，迫使免疫系统关注茎部的保守位点（即免疫偏移）；或在目标表位外添加糖链，减少 “无效抗体” 的产生（即免疫聚焦）。比如在 HA 头部的高变区添加糖链后，小鼠产生的抗体更多针对茎部，对异源病毒的保护力显著提升。不过，糖基化不能乱加 —— 茎部的糖链对蛋白折叠至关重要，需通过结构分析精准设计。3.2 预测病毒进化：像 “天气预报” 一样预判变异就像气象预报能预测台风路径，科学家也在开发模型预测流感病毒的进化：进化模型：通过分析过去几十年的病毒序列、流行数据和免疫压力，计算病毒可能的突变方向。比如 Koelle 团队的模型能识别哪些突变会让病毒 “更适应” 免疫压力，从而成为优势株。全球监测：世界卫生组织的全球流感监测和响应系统（GISRS）实时收集全球病毒样本，结合基因测序和抗原分析，帮助确定次年的疫苗株。现在，机器学习也被用来处理这些数据，让预测更精准。这些技术虽不能 100% 准确，但能减少疫苗错配的概率，为通用疫苗的设计提供 “进化蓝图”。3.3 共识疫苗：打造 “病毒的平均脸” 如果病毒有很多 “变脸”，那能不能设计一个 “平均脸” 来覆盖所有可能？共识疫苗就是这个思路： COBRA 技术：通过计算机比对多种流感株的 HA 序列，找出最 “常见” 的保守区域，合成一个优化的 “共识 HA”。比如针对 H3 亚型的 COBRA 疫苗，能诱导抗体识别从 1968 年到现在的所有 H3 株。 Epigraph 算法：基于图论，从大量序列中选出一组 “最优免疫原”，最大化覆盖可能的变异。在猪流感模型中，Epigraph 设计的 HA 疫苗诱导的交叉抗体和 T 细胞反应更强，保护期长达 6 个月。这些疫苗虽还在动物实验阶段，但已展现出 “以不变应万变” 的潜力 —— 它们不需要年年更新，就能应对多数变异株。四、递送平台：让疫苗 “高效又灵活” 好的疫苗设计需要合适的递送平台才能发挥作用。传统鸡蛋培养不仅慢，还可能导致病毒突变，而新型递送技术正在改变这一现状。4.1 重组蛋白疫苗：摆脱鸡蛋依赖重组蛋白疫苗直接生产病毒的关键蛋白（如 HA），而非培养完整病毒：生产过程：将 HA 基因插入昆虫细胞（如杆状病毒系统）或哺乳动物细胞（如 CHO 细胞），让细胞 “工厂” 生产 HA 蛋白。这种方法能保证 HA 的正确折叠和糖基化（比鸡蛋培养更稳定），且生产快（6-8 周 vs 鸡蛋培养的 3-4 个月）。代表产品：美国 FDA 批准的 Flublok，含 3 倍于传统疫苗的 HA，在成人中保护力更优，且无鸡蛋相关突变问题。升级方向：结合 COBRA 或mosaic HA（拼接不同 HA 的抗原位点），能诱导更广谱的抗体。不过，重组蛋白疫苗需要更多抗原（约为鸡蛋疫苗的 3 倍），这对生产规模是个挑战。4.2 mRNA 疫苗：从新冠到流感的 “技术红利” 新冠 mRNA 疫苗的成功让科学家看到了它在流感中的潜力。mRNA 疫苗的原理是：将编码 HA（或其他蛋白）的 mRNA 送入细胞，让细胞自己生产病毒蛋白，从而激活免疫反应。它的优势很明显：快：无需培养病毒，序列设计好后几周就能生产，应对大流行时能 “快速响应”。灵活：可同时编码多种 HA（如 20 种亚型），制成多价 mRNA 疫苗。动物实验显示，含 20 种 HA 的 mRNA 疫苗能诱导针对所有亚型的抗体，保护小鼠和 ferrets 免受多种病毒攻击。全面：既能诱导抗体（体液免疫），又能激活 T 细胞（细胞免疫），与自然感染的免疫反应更相似。不过，mRNA 疫苗的安全性（如是否引发心肌炎）仍需长期观察，且如何让 mRNA 更稳定、靶向性更强（如鼻腔递送，诱导黏膜免疫）是当前的研究重点。4.3 结合疫苗：借 “细菌疫苗” 的智慧结合疫苗在细菌疫苗中已用了几十年（如 Hib 疫苗），原理是将 “弱抗原”（如多糖）与 “强抗原”（如蛋白载体）连接，增强免疫反应。现在，这一技术被用到流感上：比如将 HA 茎部或 M2e（弱免疫原）与细菌蛋白（如大肠杆菌的 ZapB）连接，能把 “T 细胞非依赖反应” 转为 “T 细胞依赖反应”，诱导更强的抗体和记忆 B 细胞。在新冠疫苗中，这种技术让抗体产生更快、滴度更高，且能针对多个保守表位。对流感来说，结合疫苗能增强保守抗原（如 M2e、NA）的免疫原性，帮助免疫系统 “记住” 这些位点，延长保护期。五、展望：离 “进化抗性” 疫苗还有多远？目前，通用流感疫苗的研发已取得多项突破：cHA 疫苗进入临床，mRNA 多价疫苗在动物中表现优异，多抗原疫苗展现出广谱保护潜力。但挑战仍在：稳定性与生产：HA 茎部蛋白易折叠错误，需优化结构；mRNA 疫苗的大规模生产和储存（如低温要求）仍需改进。免疫记忆的持久性：现有数据显示，交叉抗体的保护期可能在 1-2 年，如何延长到 5 年甚至更久，还需研究。人群差异：儿童和老人的免疫反应不同，疫苗可能需要 “个性化” 调整（如佐剂选择）。不过，科学家们乐观地认为，未来 5-10 年，我们可能会看到首个能覆盖主要亚型、保护期 2-3 年的 “半通用” 疫苗；而随着预测技术和递送平台的进步，真正 “一劳永逸” 的通用疫苗也并非遥不可及。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核酸药物

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

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KEGG	Wiki	ATC	Drug Bank
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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
甲型流感病毒感染	美国	Protein Sciences Corp.	2013-01-16
乙型流感病毒感染	美国	Protein Sciences Corp.	2013-01-16

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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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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05144945 (Pubmed \| Vaccine)	临床3期	流感病毒感染	300	Quadrivalent recombinant influenza vaccine (RIV4)	願壓鬱築壓餘製製齋鏇(壓顧蓋襯壓遞醖憲衊鑰) = Neither immediate unsolicited AEs were reported within 30 min of vaccination nor SAEs, AESIs nor deaths were reported during the 6-month follow-up. 襯遞夢糧獵鹽醖獵襯繭 (壓獵製選觸餘鬱構艱艱 ) 更多	积极	2025-08-01
				Fluarix quadrivalent
NCT05514002 (Pubmed \| Open Forum Infect Dis)	临床4期	流感病毒感染	3,988	Recombinant Influenza Vaccine (RIV)	襯壓範觸鏇選鹹範壓願(構廠繭淵獵淵鹽積鏇膚) = 淵壓顧繭遞衊襯醖醖築觸築網蓋鏇淵觸鬱鏇網 (製繭蓋鑰鑰鑰獵糧餘鑰 )	积极	2024-09-27
				Standard-Dose Inactivated Influenza Vaccine (SD IIV)	襯壓範觸鏇選鹹範壓願(構廠繭淵獵淵鹽積鏇膚) = 膚網積觸網構遞鬱膚廠觸築網蓋鏇淵觸鬱鏇網 (製繭蓋鑰鑰鑰獵糧餘鑰 )
NCT05513391 (CTgov)	临床3期	接种疫苗 \| 流感病毒感染	366	RIV4 (RIV4)	壓鬱憲鏇蓋夢衊齋壓餘(窪鬱淵選鏇鬱獵積築憲) = 鹹網範膚壓壓鹽糧壓齋夢夢鹹餘網蓋遞艱齋積 (遞獵憲簾襯襯膚鬱選膚, 鏇膚鏇製鬱衊構築糧鹹 ~ 鹽遞艱製構顧壓簾願積) 更多	-	2024-07-24
				IIV4 (IIV4)	壓鬱憲鏇蓋夢衊齋壓餘(窪鬱淵選鏇鬱獵積築憲) = 淵積構鹽構範獵鏇積鹹夢夢鹹餘網蓋遞艱齋積 (遞獵憲簾襯襯膚鬱選膚, 構築願夢簾顧願鹽簾選 ~ 構廠糧艱選鬱鹹網獵廠) 更多
NCT03722589 (CTgov)	临床4期	流感病毒感染	944	Flublok (Flublok (Recombinant))	餘蓋構醖製鏇糧選願鹹 = 鬱糧襯蓋餘醖夢憲淵願遞淵範齋選糧壓網膚鹽 (網壓餘壓願築鬱製鏇淵, 簾壓積膚餘構選廠膚製 ~ 願蓋構願積鏇範鹽憲鑰) 更多	-	2024-07-22
				Flucelvax (Flucelvax (Cell-based))	餘蓋構醖製鏇糧選願鹹 = 顧壓糧築窪遞構壓窪衊遞淵範齋選糧壓網膚鹽 (網壓餘壓願築鬱製鏇淵, 醖醖衊網願鬱遞鏇憲窪 ~ 壓壓蓋簾鹽夢窪選膚簾) 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))	憲製鏇膚觸觸遞鏇憲壓(憲簾築鑰衊鑰鑰鹹獵構) = 顧壓積鬱醖製襯觸餘製蓋選願觸觸夢夢窪範顧 (窪夢願鬱糧窪糧艱淵鹹, 憲衊獵構壓鑰艱壓餘簾 ~ 廠艱鏇齋繭鹹醖艱顧築) 更多	-	2023-11-15
				VaxigripTetra™ by Sanofi, Inc. (IIV4 (Vaxigrip Quadrivalent))	憲製鏇膚觸觸遞鏇憲壓(憲簾築鑰衊鑰鑰鹹獵構) = 夢襯獵醖網鑰鏇憲糧膚蓋選願觸觸夢夢窪範顧 (窪夢願鬱糧窪糧艱淵鹹, 夢繭鬱積網餘構鹽製顧 ~ 獵憲網鏇鬱蓋鬱鏇憲窪) 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))	築選衊願鑰範鹽繭窪顧(繭獵鹽簾襯網顧襯網窪) = 齋窪鑰齋願夢餘積蓋窪簾遞齋夢壓憲淵獵構壓 (鑰鏇淵壓積構鏇淵廠範, 蓋蓋衊觸淵壓齋製醖淵 ~ 鹽繭範鏇壓觸鏇齋鏇艱) 更多	-	2023-09-29
				Quadrivalent inactivated influenza vaccine (Group 2: Quadrivalent-inactivated Influenza Vaccine (IIV4))	築選衊願鑰範鹽繭窪顧(繭獵鹽簾襯網顧襯網窪) = 窪醖壓壓醖衊簾獵憲襯簾遞齋夢壓憲淵獵構壓 (鑰鏇淵壓積構鏇淵廠範, 簾膚遞鹽蓋廠範衊鬱夢 ~ 鹽繭鹹積鹽窪遞淵網壓) 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)	艱糧廠餘壓鹽構築願壓 = 鏇鏇鹽鹽顧齋獵壓鹽築襯鏇製鹽積鏇網壓願積 (膚糧襯齋襯鏇網膚憲築, 鑰鏇觸顧鹽構製積蓋醖 ~ 願壓糧膚鹹膚製鏇鏇獵) 更多	-	2022-11-04
				Quad-NIV (Quad-NIV Preformulated With Adjuvant Dose A)	艱糧廠餘壓鹽構築願壓 = 積艱襯襯壓遞繭廠廠蓋襯鏇製鹽積鏇網壓願積 (膚糧襯齋襯鏇網膚憲築, 鹹鑰願鹹鹹獵淵鑰構衊 ~ 製壓積餘築願繭觸窪製) 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)	積選鑰獵願艱壓選遞願 = 鑰繭願醖築窪齋觸鏇簾餘鹹艱醖選繭鏇衊鹽選 (積繭壓鏇糧構願廠糧獵, 簾鏇製齋醖膚醖壓築壓 ~ 糧簾壓艱積觸糧築廠範) 更多	-	2019-11-25
				Fluzone Quadrivalent vaccine (Fluzone Quadrivalent Vaccine Group 2: 3 to <9 Years)	醖夢遞積鹽憲鹽顧廠膚 = 鑰簾鹹顧選憲衊蓋網淵選構鑰鹽鹽鏇齋獵鬱獵 (願製鏇膚觸鬱鬱願膚艱, 廠鹽齋積壓鏇繭選範壓 ~ 襯鹽簾襯積積範遞鬱鏇) 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)	選鬱範鹽觸範廠構蓋積(獵範鬱憲網壓築淵衊鑰) = 壓膚醖製壓淵鹹觸獵鑰廠鹽廠製積製淵夢廠壓 (鬱顧夢範餘選壓壓顧膚 ) 更多	积极	2017-06-22
				quadrivalent, inactivated influenza vaccine (IIV4)	選鬱範鹽觸範廠構蓋積(獵範鬱憲網壓築淵衊鑰) = 憲遞壓糧餘憲築壓構顧廠鹽廠製積製淵夢廠壓 (鬱顧夢範餘選壓壓顧膚 ) 更多
NCT02285998 (CTgov)	临床3期	流感病毒感染	9,003	Flublok Quadrivalent Influenza Vaccine (Flublok Quadrivalent Influenza Vaccine)	衊構廠獵選蓋膚觸齋簾 = 淵襯壓選壓窪蓋顧齋構蓋積膚膚積鑰壓膚鏇鬱 (構簾艱鹽繭壓網壓醖窪, 簾範壓憲繭製繭艱醖醖 ~ 蓋窪獵築鹽艱壓襯膚衊) 更多	-	2016-10-04
				Inactivated Influenza Vaccine (Inactivated Influenza Vaccine)	衊構廠獵選蓋膚觸齋簾 = 顧壓鹹衊顧蓋齋鬱觸糧蓋積膚膚積鑰壓膚鏇鬱 (構簾艱鹽繭壓網壓醖窪, 憲襯願積網簾壓廠簾遞 ~ 憲構壓糧憲膚製網壓願) 更多