Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine (Butantan-DV) in Patients With Autoimmune Rheumatic Diseases Living in Dengue-Endemic Areas

The goal of this clinical trial is to evaluate whether the live attenuated tetravalent Butantan-Dengue vaccine (Butantan-DV) is safe and capable of inducing an immune response in patients aged 7 to 59 years with autoimmune rheumatic diseases (ARDs) who are clinically stable and under low-grade or no immunosuppression, as well as in healthy volunteers matched by sex and age.
The main questions it aims to answer are:
Does the vaccine induce adequate seroconversion in patients with ARDs compared to healthy controls? What is the frequency and intensity of common adverse events after vaccination in ARDs patients? Researchers will compare patients with ARDs to healthy controls to evaluate if the vaccine elicits similar immune responses and safety profiles.
All participants will:
* receive a single 0.5 mL dose of the Butantan-DV vaccine via subcutaneous injection;
* undergo blood sample collection before and after vaccination (baseline, Day 42, and Day 400) to assess antibody and cellular responses;
* attend follow-up visits on Days 7, 14, and 42 for safety monitoring and laboratory tests;
* report any symptoms or adverse events using a standardized diary for 42 days;
* be followed for up to one year for long-term safety and immunogenicity assessments.
Researcher will also perform subgroups analysis in:
A viremia subgroup (50 patients and 50 healthy controls) will provide additional samples on Days 1, 7, 14, 28, 42, and-if viremia is detected-Day 68, to evaluate post-vaccination viremia and its duration.
An immunogenicity subgroup (
20% of participants) will undergo cellular immune response testing via flow cytometry to evaluate T-cell responses.

开始日期2025-08-01

申办/合作机构

University of Sao Paulo General Hospital

[+1]

NCT06891950

/ Not yet recruiting临床3期IIT

Phase 3B, Double-blind, Randomized Study to Evaluate the Safety and Non-inferiority of the Humoral Immune Response of the Butantan Dengue Vaccine in Participants Aged 60 to 79 Years Compared to Participants Aged 40 to 59 Years

This is a randomized, double-blind (60 -79 years) and open-label (40-59 years), three-arm parallel Phase 3b, multicenter study to evaluate the safety and non-inferiority of the humoral immune response of the Butantan Dengue vaccine (Dengue 1,2,3,4 (attenuated)) in participants aged 60 -79 years (elderly) compared to participants aged 40 to 59 years (adults), with or without previous dengue and healthy based on clinical examination.

开始日期2025-07-01

申办/合作机构

Instituto Butantan

[+1]

NCT05710224

/ Completed临床2期IIT

A Phase 2, Randomized, Double-Blind, Multicenter, Safety and Immunogenicity Clinical Bridging Study to Compare V181 (Dengue Quadrivalent Vaccine rDENVΔ30 [Live, Attenuated]) to Butantan Dengue Vaccine (Butantan-DV) in Healthy Adults 18 to 50 Years of Age in Brazil

The purpose of this study is to demonstrate that V181 is safe and well tolerated and elicits an immune response that is non-inferior to that of Butantan-DV at Day 28 post-vaccination in adults 18 to 50 years of age in Brazil. The primary hypothesis is that V181 is non-inferior to Butantan-DV for each of the 4 dengue serotypes based on geometric mean titers (GMTs) and seroconversion rates at Day 28 post-vaccination.

开始日期2023-02-15

申办/合作机构

Instituto Butantan

[+1]

100 项与 Tetravalent dengue virus vaccine(Instituto Butantan) 相关的临床结果

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100 项与 Tetravalent dengue virus vaccine(Instituto Butantan) 相关的转化医学

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100 项与 Tetravalent dengue virus vaccine(Instituto Butantan) 相关的专利（医药）

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项与 Tetravalent dengue virus vaccine(Instituto Butantan) 相关的文献（医药）

2025-08-01·JOURNAL OF INVESTIGATIVE DERMATOLOGY

Localized Inflammation in Dengue Vaccine–Induced Skin Rash Is Not Associated with Continuous Presence of Dengue Virus Genome

Article

作者: Graham, Nancy R ; Durbin, Anna P ; Pierce, Kristen K ; Sabundayo, Beulah ; Strother, Camilla ; Greene, Laura ; Bouffard, Nicole ; Taatjes, Douglas J ; Smolynets, Olha ; Diehl, Sean A ; Elko, Evan A ; Kirkpatrick, Beth D ; Whitehead, Stephen S

Vaccination with the tetravalent live-attenuated dengue virus (DENV) vaccines TV003 and TV005 causes a mild, relatively localized erythematous maculopapular skin rash in most dengue-naïve vaccinees. Human challenge model DENV strains, DENV2Δ30 and DENV3Δ30, trigger a confluent skin rash over most of the body in most unvaccinated participants. To determine the etiology of these rashes, we performed in situ hybridization for DENV genome and assessed cellular infiltration by H&E staining in skin biopsies from humans infected with live-attenuated dengue vaccine DENV2Δ30 or DENV3Δ30 challenge strains. Sixty-three biopsies from 40 participants were included in the study, of which 43 biopsies from 32 patients contained intact RNA. Of these, 1 sample taken from a nonerythematous site from a DENV2Δ30-infected participant experiencing a rash was positive for DENV2 genome. Incidence and severity of lymphocytic infiltration were highest in rash biopsy samples than in those from noninvolved areas in participants experiencing a rash or from those taken from participants not experiencing a rash. These results indicate that the rash associated with infection with live-attenuated dengue vaccines or challenge strains is predominantly lymphocyte-driven perivascular dermal inflammation without local concomitant active viral replication.

2025-03-01·VIRAL IMMUNOLOGY

Advances in the Epidemiology, Pathogenesis, Diagnostic Methods, and Vaccine Development of Dengue Fever: A Comprehensive Review

Review

作者: Feng, Xianmin ; Feng, Sisi ; Dong, Boqi

Dengue fever (DF) is a common mosquito-borne viral infection caused by any of the four dengue virus (DENV) serotypes. In recent years, the global incidence of DF has risen rapidly, which has widely threatened the health of millions of people in the United States, Southeast Asia, and the Western Pacific. The challenges for the prevention and control of DENV infection have become increasingly severe. Over the years, advances in the area of DF research have been continuously updating. In this review, we provide an updated and more in-depth overview of dengue epidemiology and pathogenesis, along with recent progress in diagnostic approaches (including methods to address cross-reactivity with other flaviviruses) and an expanded discussion of current dengue vaccine development, such as CYD-TDV (Dengvaxia), TV003/TV005, and the new TAK-003. This comprehensive perspective aims to offer references for the prevention, clinical diagnosis, and control of the disease.

2024-06-01·Health Science Reports

Immunization against dengue virus infection is coercive: A timely call

Article

作者: Dewan, Syed M R ; Ahmed, Iftekhar ; Nahar, Shamsun ; Ahamed, Rayhan ; Bari, Lazima F

Abstract:

Background:

In context, the dengue virus causes dengue fever, which is spread by mosquito bites. About 22,000 people every year lose their lives as a direct result of it. Dengue fever has been on the rise recently, and its spread has alarmed health officials throughout the world.

Discussion:

Vaccination is essential for the prevention and management of dengue cases because there is currently no particular cure against dengue virus. The current dengue epidemic calls for urgent action in the form of immunization. However, there are serious drawbacks to using existing vaccines like Dengvaxia. Besides, the Qdenga vaccine has not yet been approved by the FDA in the United States. On the other hand, positive results from a phase II randomized and controlled clinical study of the TV005 tetravalent live‐attenuated dengue vaccine were recently reported in Bangladesh. Only an effective vaccination can drastically lower dengue infection and mortality rates.

Conclusion:

The development of safe and effective vaccination, as well as their correct dissemination, is an essential requirement for the people of Bangladesh and the rest of the globe, and we concentrated on this critical problem in this article.

项与 Tetravalent dengue virus vaccine(Instituto Butantan) 相关的新闻（医药）

2025-07-13

·ETPharma

Phase-3 clinical trial enrolment for India's first dengue vaccine to be completed by October: ICMR

New Delhi: Enrolment of about 10,500 participants in the phase III clinical trial of the indigenous one-shot Panacea Biotec developed dengue vaccine, DengiAll, is likely to be completed by October across 20 centres in India, according to ICMR scientists. So far, 8,000 participants in various centres at Pune, Chennai, Kolkata, Delhi and Bhubaneswar among others have received either the vaccine or a placebo as part of the trial sponsored by the Indian Council of Medical Research (ICMR) and Panacea Biotec. The trial is co-led by ICMR-National Institute of Translational Virology and AIDS research in Pune, National Institute of Epidemiology (NIE), Chennai and National Institute of Virology, Pune. Currently, there is no antiviral treatment or licensed vaccine against dengue in India. The results of the Phase-1/2 trial has shown no safety concerns for the one-shot vaccine, NIE Director Dr Manoj Murhekar said. "The participants enrolled in the Phase- III trial will be followed up for two-years. This trial will evaluate the efficacy of this tetravalent dengue vaccine," Dr Murhekar said. The multi-centre, double-blind, randomised, placebo-controlled phase-III trial was launched in August last year to evaluate the jab's efficacy, safety and, long-term immunogenicity. The first participant in this trial was vaccinated at the Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences (PGIMS), Rohtak last year. The development of an effective vaccine is complex due to the need to achieve good efficacy for all four serotypes. The dengue virus has four serotypes, 1-4, with low cross-protection against each other, meaning individuals can experience repeated infections, Dr Murhekar said. In India, all four serotypes of dengue virus are known to circulate or co-circulate in many regions. The Union Health Ministry in a statement earlier had said that the tetravalent dengue vaccine strain (TV003/TV005), originally developed by the National Institutes of Health (NIH), USA, has shown promising results in clinical trials in Brazil. Panacea Biotec, one of three Indian companies to receive the strain, is at the most advanced stage of development. The company has worked extensively on these strains to develop a full-fledged vaccine formulation and holds a process patent for this work. Dengue is a major public health concern in India, ranking among the top 30 countries with the highest incidence of the disease. The global incidence of dengue has been steadily increasing over the past two decades, with more than 129 countries reporting dengue viral disease by the end of 2023, according to the World Health Organisation (WHO). In India, approximately 75-80 per cent of infections are asymptomatic, yet these individuals can still transmit the infection through the bite of Aedes mosquitoes. Among the 20-25 per cent of cases where symptoms are clinically apparent, children are at a significantly higher risk of hospitalisation and mortality. In adults, the disease can escalate into severe conditions like dengue hemorrhagic fever and dengue shock syndrome. According to the government data, around 12,043 dengue cases were reported till March this year. In 2024, 2.3 lakh cases and 297 deaths had been recorded.

临床3期疫苗

2025-05-09

·药时空

突破在即！全球登革热疫苗研发最新进展盘点

登革热是全球影响范围最广的节肢动物媒介疾病，主要通过埃及伊蚊或白纹伊蚊传播，全球有近一半的人口面临感染的风险。目前，还没有通用的抗登革病毒药物。登革热的流行病学特征复杂，临床表现多样，从无症状感染到危及生命的登革出血热，任何一种DENV血清型（DENV-1、DENV-2、DENV-3、DENV-4）都可能导致不同程度的疾病。感染一种血清型可对相同血清型产生长期免疫力，对其他血清型仅有短暂免疫力，连续感染不同血清型会使重症登革热的风险增加。登革热病例通常无症状或导致轻度发热性疾病。然而，有些病例会发展为重症登革热，可能会出现休克、严重出血或严重器官损伤。这一阶段通常在退烧后开始，之前有一些警告信号，如剧烈腹痛、持续呕吐、牙龈出血、积液、嗜睡或烦躁以及肝脏肿大[1]。据估计，全球每年有超过1亿至4亿例登革热病例，38亿人生活在登革热流行国家，其中大部分位于非洲、美洲和亚洲。2023年报告的登革热病例数最多，世卫组织美洲区域报告了450万例病例和2300例死亡。由于气候变化和城市化，登革热病例可能还会上升并在地理上出现扩大[2]。我国2019—2023年共报告病例43095例，平均报告发病率为0.61/10万，年报告发病率波动显著（AAPC=-3.16%，95% CI：-54.16%~91.47%），主要集中在2019年和2023年，约占近5年总报告病例数的96.83%。各年龄组人群均可发病，30~<40岁年龄组病例占22.6%。全年均有病例发生，6月份开始快速上升，高峰期集中在8—10月份，为34 780例（RR=12.44，LLR=29 262.52，P<0.05）。疫情特征以输入引发本地传播为主，输入病例主要来源于东南亚地区（占86.56%），其中柬埔寨3284例（占46.11%）、缅甸1851例（占25.99%）为病例主要来源国家。不同年份有显著不同，西南地区、华南地区、华东地区发生本地传播疫情风险高，高发地区主要分布在云南和广东[3]。近几十年来，持续的登革热疫情对维护全球公共卫生安全带来了艰巨的挑战，公众迫切需要一种安全有效的登革热疫苗。对于DENV，有效的疫苗必须对4种DENV血清型都产生免疫保护，又要尽可能避免异源血清型继发感染导致ADE效应。目前，进入临床试验阶段的登革热疫苗主要有减毒活疫苗、灭活病毒疫苗、DNA疫苗、重组亚单位疫苗等。详细情况见下表：赛诺菲巴斯德公司研发的四价减毒活疫苗CYD-TDV是首个上市的登革热疫苗，该疫苗以黄热减毒活疫苗（YFV17D）为骨架，用DENV的前体膜蛋白（prM）和包膜蛋白（E）基因取代YFV 17D相应的结构蛋白基因构建而成[4]。TAK-003是由武田制药开发的一种四价登革热减毒活疫苗，最近已获准在欧盟和印度尼西亚用于6~45岁人群预防接种，且无论其血清阳性或阴性都可接种[5]-[6]。目前，TAK-003正在亚洲、拉丁美洲及其他登革热流行国家接受监管审查[7]。武田制药正在开展一项新的临床试验（NCT03999996），以评估第1次接种15个月和24个月后加强接种的效用。结果表明，TAK-003中来自DENV-2骨架的NS被证明可以引发NS特异性T细胞免疫，所以该疫苗对DENV-2（病毒骨架的起源株）的保护效果最高，这表明未来DENV疫苗研发要同时考虑特异性抗体和T细胞表位产生的免疫影响[8]。TV003/TV005是由美国国家过敏与传染病研究所（NIAID）研制的一种处于临床试验阶段的减毒活疫苗。其研发策略主要分为两种：第一种是在3′非翻译区引入30个核苷酸缺失来设计疫苗（rDEN1Δ30、rDEN3Δ30、rDEN4Δ30）[9]；第二种是用DENV-2的prM和E蛋白替代rDEN4Δ30中的prM和E蛋白[10]。TV003 （103 PFU）和TV005（104 PFU的主要差异在于rDEN2/4Δ30组分用量不同。当不同血清型DENV继发感染宿主时，体内预存的DENV抗体会促进第2种DENV进入单核细胞和巨噬细胞。DENV首先与抗体的Fc片段结合，然后在宿主细胞FcγRs（特别是FcγR Ⅱa和FcγR Ⅲa）的介导下进行吸附和侵袭，并抑制Ⅰ型干扰素的产生，从而增强宿主细胞内病毒的复制[11]。交叉免疫应答抗体可以介导同属病毒的ADE效应。几乎所有抗DENV抗体都可以诱导寨卡病毒（ZIKV）感染的ADE效应[12]。交叉免疫应答的非中和抗体识别两种主要的抗原表位，分别是prM蛋白表位和E蛋白上的融合环表位（FLE）。Dai等[13]通过改变FLE构象但保留其中和表位，重新设计了ZIKV亚单位疫苗免疫原。研究发现，免疫诱导的抗体不会与DENV发生交叉反应，这是消除ZIKV感染导致ADE效应的重大突破。与基于野生型毒株的疫苗相比，该疫苗产生的抗体反应具有更好的免疫优势。野生型毒株疫苗引发的抗体反应主要集中在特定的抗体基因上，而此抗体反应更为多样和分散。这意味着此二聚体疫苗能够改变对ZIKV的免疫优势，在免疫应答中减少了与ADE效应相关的抗体反应。晶体结构表明，免疫原二聚体的E蛋白片段在形成过程中被改变，抑制了ADE效应，为避免产生ADE效应的DENV疫苗研发提供了一种思路[14]。参考文献：[1]世界卫生组织.登革热-全球形势[EB/OL].(2023-12-21) [2025-04-08].https://www.who.int/zh/emergencies/disease-outbreak-news/item/2023-DON498.[2] 世界卫生组织.世卫组织预认证新型登革热疫苗[EB/OL].(2024-05-15) [2025-04-08].https://www.who.int/zh/news/item/15-05-2024-who-prequalifies-new-dengue-vaccine.[3] 李卓威, 黄晓霞, 田婷婷, 等. 我国2019—2023年登革热报告病例流行病学特征. 中国热带医学. 2024, 24(8): 925-930 https://doi.org/10.13604/j.cnki.46-1064/r.2024.08.07.[4] Guy B, Saville M, Lang J. Development of Sanofi Pasteur tetravalent dengue vaccine[J]. Hum Vaccin, 2010, 6(9).[5]Takeda’s QDENGA®▼ (Dengue Tetravalent Vaccine [Live, Attenuated]) Approved for Use in European Union [EB/OL]. (2022-08-22) [2025-04-15]. https://www.takeda.com/newsroom/newsreleases/2022/takedas-qdenga-dengue-tetravalent-vaccine-live-attenuated-approved-for-use-in-european-union/.[6]Takeda’s QDENGA®▼ (Dengue Tetravalent Vaccine [Live, Attenuated]) Approved for Use in European Union [EB/OL]. (2022-12-08) [2025-04-15]. https://www.takeda.com/newsroom/newsreleases/2022/takedas-qdenga-dengue-tetravalent-vaccine-live-attenuated-approved-for-use-in-european-union/.[7]Takeda comienza con las presentaciones regulatorias para la vacuna candidata contra el dengue en la UE y los países endémicos[EB/OL]. (2021-04-01) [2025-04-15]. https://www.takeda.com/es-ar/prensa/2021/takeda-comienza-con-las-presentaciones-regulatorias-para-la-vacuna-candidata-contra-el-dengue-en-la-ue-y-los-paises-endemicos/.[8] Tricou V, Gottardo R, Egan MA, et al. Characterization of the cell-mediated immune response to Takeda′s live-attenuated tetravalent dengue vaccine in adolescents participating in a phase 2 randomized controlled trial conducted in a dengue-endemic setting[J]. Vaccine, 2022, 40 (8): 1143-1151.[9] Durbin AP, Kirkpatrick BD, Pierce KK, et al. Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine[J]. Vaccine, 2011, 29(42): 7242-7250.[10] Whitehead SS, Hanley KA, Blaney JE Jr, et al. Substitution of the stru识别微信二维码，可添加药时空小编请注明：姓名+研究方向！

疫苗临床研究

2025-04-15

·药时空

登革热疫苗进展：下一代候选疫苗的历史概述和前景

登革热是由登革病毒（DENV）引起的蚊媒传染病，全球近一半人口受威胁，每年大量发病和死亡。DENV 有 4 种血清型，其基因组编码多种蛋白，E 蛋白是主要免疫原，NS1 蛋白可用于疫苗研究，感染后可能引发抗体依赖增强（ADE）现象，导致病情加重。 1、现有疫苗类型及进展减毒活疫苗：Dengvaxia® 和 Qdenga® 已获批，TV003/TV005 完成 III 期临床试验。它们能诱导较强免疫反应，但存在对不同血清型保护效力不均衡、受个体免疫状态和年龄影响等问题。灭活疫苗：安全性高，但免疫原性较弱。目前多种候选疫苗处于临床试验阶段，通过改进灭活技术、使用新型佐剂等可提升免疫原性和保护效果。重组亚单位疫苗：副作用小、易于生产，但免疫原性相对较弱。不同表达系统生产的疫苗在动物模型和临床试验中展现出一定潜力，未来需进一步优化。病毒样颗粒（VLPs）疫苗：能诱导体液和细胞免疫反应，但适用范围有限。多种 VLPs 疫苗在不同表达系统中进行研究，显示出对多种血清型的中和抗体诱导能力。重组病毒载体疫苗：虽未进入临床试验阶段，但多种病毒载体在研究中表现出良好效果，能诱导强免疫反应，未来病毒载体的选择和改造至关重要。核酸疫苗：DNA 疫苗和 mRNA 疫苗在动物模型和临床试验中显示出一定保护效果，但存在免疫原性和储存稳定性等问题。新的递送方法和合理的抗原设计有望推动其发展。 2、未来发展策略应对 ADE 策略：包括选择特定抗原表位、设计特定免疫反应、避免免疫优势表位、使用突变或修饰抗原、采用非结构蛋白作为抗原、优化疫苗配方和佐剂等。初免 - 加强策略：不同类型疫苗联合使用的初免 - 加强方案可诱导更高且持久的中和抗体反应，提供更全面的保护。免疫信息学助力疫苗设计：利用生物信息学工具可识别保守区域，设计多表位疫苗，提高疫苗的免疫原性和安全性。阻断感染传播策略：释放携带沃尔巴克氏体的蚊子和研发传播阻断疫苗可有效减少病毒传播，疫苗接种应与其他防控措施相结合。

疫苗信使RNA

100 项与 Tetravalent dengue virus vaccine(Instituto Butantan) 相关的药物交易

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研发状态

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
登革热	申请上市	-	Instituto Butantan	-
抗磷脂综合征	临床3期	巴西	Instituto Butantan	2025-08-01
银屑病关节炎	临床3期	巴西	Instituto Butantan	2025-08-01
中轴性脊柱关节炎	临床3期	巴西	Instituto Butantan	2025-08-01
白塞病/贝赫切特综合征	临床3期	巴西	Instituto Butantan	2025-08-01
肉芽肿伴多血管炎	临床3期	巴西	Instituto Butantan	2025-08-01
特发性炎症性肌病	临床3期	巴西	Instituto Butantan	2025-08-01
幼年特发性关节炎	临床3期	巴西	Instituto Butantan	2025-08-01
显微镜下多血管炎	临床3期	巴西	Instituto Butantan	2025-08-01
类风湿关节炎	临床3期	巴西	Instituto Butantan	2025-08-01

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适应症

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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


NCT02678455 (TV005, CTgov)	临床2期	登革热	192	TV005 vaccine (TV005 Vaccine)	觸夢積獵網壓選艱構願 = 簾選糧選襯鑰願艱願餘壓餘蓋艱繭餘醖願廠構 (顧憲餘衊觸鏇製衊範鑰, 鹽築鹽壓壓窪鬱選鬱鹽 ~ 衊鹽選願廠獵繭鹽醖網) 更多	-	2025-01-17
				Placebo (Placebo)	觸夢積獵網壓選艱構願 = 構繭艱積獵艱蓋範淵衊壓餘蓋艱繭餘醖願廠構 (顧憲餘衊觸鏇製衊範鑰, 衊製窪選淵鹹簾鑰獵範 ~ 廠製襯鑰齋淵窪鑰鏇積) 更多
NCT02678455 (Pubmed \| Lancet Infect Dis) 人工标引	临床2期	登革热	192	TV005 vaccine	繭窪構願網淵顧壓鬱積(製遞壓選膚憲壓艱壓齋) = 遞蓋廠範獵淵廠選鏇築選鬱繭憲遞觸製繭膚鏇 (憲齋鏇壓鬱壓艱遞壓鹽 ) 更多	积极	2024-02-01
				Placebo	鏇選鏇網醖鑰膚糧窪簾(鑰膚蓋餘壓築遞網艱範) = 衊憲齋艱簾鹽淵衊憲選構艱顧醖繭衊襯積齋憲 (簾餘餘蓋鹹餘範壓齋醖, 2.4)
NCT01506570 (Pubmed \| PLoS Negl Trop Dis)	临床1期	黄病毒感染	58	TV003 vaccine	構構艱餘鹽遞鹽簾鹽願(願鏇鹹積觸網齋憲齋鹹) = few adverse events other than rash, which was predominately mild 鹹鏇範鹹窪積積觸憲蓋 (鹹膚鑰簾憲構選製壓蓋 )	-	2017-05-01