更新于：2024-06-21

Tuberculosis vaccine H56IC(Statens Serum Institute)

更新于：2024-06-21

概要

研发状态

概要

基本信息

药物类型

预防性疫苗

别名

Adjuvanted TB subunit vaccine H56IC、H56/IC31 vaccine、Tuberculosis vaccine H56IC

+ [6]

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

结核肺结核

非在研适应症

潜伏性结核耐多药肺结核

原研机构

Statens Serum Institute

在研机构

International AIDS Vaccine Initiative, Inc.

Aeras Technologies LLC

European & Developing Countries Clinical Trials Partnership

+ [1]

非在研机构

Aj Vaccines A/S

Aeras Global TB Vaccine Foundation

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

项与 Tuberculosis vaccine H56IC(Statens Serum Institute) 相关的临床试验

PACTR201808711101850 / Unknown status临床2期

A Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of H56:IC31 in Reducing the rate of TB Disease Recurrence in HIV Negative Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis

开始日期2019-04-01

申办/合作机构

Statens Serum Institute

NCT03512249 / Active, not recruiting临床2期IIT

Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Evaluate Safety and Efficacy of H56:IC31 in Reducing the Rate of TB Disease Recurrence in HIV Negative Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis

This is a phase 2, double-blind, randomized (1:1), placebo-controlled trial with two parallel groups.
H56:IC31 (investigational vaccine)
Placebo
900 HIV-negative adults with a diagnosis of drug susceptible pulmonary TB are planned to be included, recruited from TB clinics with established relationships to the trial sites at the start of their TB treatment.
5 study sites in South Africa: 2 sites from the AURUM institute (Klerksdorp and Tembisa) and 3 in Cape Town at TASK Applied Science (TASK), the University of Cape Town Lung Institute (UCTLI) and South African Tuberculosis Vaccine Initiative (SATVI) under UCT, respectively.
1 study site in Tanzania (TZ): 1 site at Mbeya Medical Research Centre (MMRC) under the National Institute for Medical Research (NIMR).

开始日期2019-01-31

申办/合作机构

International AIDS Vaccine Initiative, Inc.

[+6]

NCT03265977 / Withdrawn临床2期

A Randomized, Placebo Controlled, Double-Blind Phase II Study to Evaluate Safety, Immunogenicity, and Prevention of Infection With Mycobacterium Tuberculosis (Mtb) of H56:IC31 in Healthy Adolescents

This clinical trial will evaluate safety, immunogenicity, and efficacy (prevention of Mtb infection as measured by IGRA conversions) of H56:IC31 in remotely BCG vaccinated adolescents.

开始日期2018-06-01

申办/合作机构

Aeras Global TB Vaccine Foundation

[+7]

100 项与 Tuberculosis vaccine H56IC(Statens Serum Institute) 相关的临床结果

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100 项与 Tuberculosis vaccine H56IC(Statens Serum Institute) 相关的转化医学

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100 项与 Tuberculosis vaccine H56IC(Statens Serum Institute) 相关的专利（医药）

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项与 Tuberculosis vaccine H56IC(Statens Serum Institute) 相关的文献（医药）

2020-06-01·Seminars in immunopathology2区 · 医学

Towards new TB vaccines

2区 · 医学

Review

作者: McShane, Helen ; Brazier, Benedict

Abstract:

Mycobacterium tuberculosisremains the leading cause of death attributed to a single infectious organism. Bacillus Calmette-Guerin (BCG), the standard vaccine againstM. tuberculosis, is thought to prevent only 5% of all vaccine-preventable deaths due to tuberculosis, thus an alternative vaccine is required. One of the principal barriers to vaccine development againstM. tuberculosisis the complexity of the immune response to infection, with uncertainty as to what constitutes an immunological correlate of protection. In this paper, we seek to give an overview of the immunology ofM. tuberculosisinfection, and by doing so, investigate possible targets of vaccine development. This encompasses the innate, adaptive, mucosal and humoral immune systems. Though MVA85A did not improve protection compared with BCG alone in a large-scale clinical trial, the correlates of protection this has revealed, in addition to promising results from candidate such as VPM1002, M72/ASO1E and H56:IC31 point to a brighter future in the field of TB vaccine development.

2020-04-01·Medical microbiology and immunology4区 · 医学

Toll like-receptor agonist Pam3Cys modulates the immunogenicity of liposomes containing the tuberculosis vaccine candidate H56

4区 · 医学

Article

作者: Löffler, Florian ; Christensen, Dennis ; Grieshober, Mark ; Mayer, Daniel ; Pedersen, Gabriel Kristian ; Kennerknecht, Kathrin ; Stenger, Steffen ; Wehrstedt, Stephanie ; Noschka, Reiner

Abstract:

A major roadblock in the development of novel vaccines is the formulation and delivery of the antigen. Liposomes composed of a dimethyldioctadecylammonium (DDA) backbone and the adjuvant trehalose-6-6-dibehenate (TDB, termed “cationic adjuvant formulation (CAF01)”, promote immunogenicity and protective efficacy of vaccines, most notably against infection with Mycobacterium tuberculosis. Specifically, the multicomponent antigen H56 delivered by CAF01 protects against tuberculosis in mice. Here we investigated whether the inclusion of immune-modulatory adjuvants into CAF01 modulates the immunogenicity of H56/CAF01 in vitro and in vivo. Based on our recent findings we selected the active sequence of the mycobacterial 19 kDa lipoprotein, Pam3Cys, which interacts with Toll like receptor 2 to induce an antimicrobial pathway. H56/CAF01-Pam3Cys liposomes were characterized for Pam3Cys incorporation, size, toxicity and activation of primary human macrophages. Macrophages efficiently take up H56/CAF01-Pam3Cys and trigger the release of significantly higher levels of TNF, IL-12 and IL-10 than H56/CAF01 alone. To evaluate the immunogenicity in vivo, we immunized mice with H56/CAF01-Pam3Cys and measured the release of IFN-γ and IL-17A by lymph node cells and spleen cells. While the antigen-specific production of IFN-γ was reduced by inclusion of Pam3Cys into H56/CAF01, the levels of IL-17A remained unchanged. In agreement with this finding, the concentration of the IFN-γ-associated IgG2a antibodies in the serum was lower than in H56/CAF01 immunized animals. These results provide proof of concept that Toll like-receptor agonist can be included into liposomes to modulate immune responses. The discordant results between the in vitro studies with human macrophages and in vivo studies in mice highlight the relevance and complexity of comparing immune responses in different species

2020-04-01·EClinicalMedicine

A phase 1b randomized study of the safety and immunological responses to vaccination with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents in Cape Town, South Africa

Article

作者: Andersen, Peter L ; Randhawa, April K ; Tait, Dereck ; Fiore-Gartland, Andrew ; Bekker, Linda-Gail ; Hutter, Julia ; Kromann, Ingrid ; Kublin, James G ; Rutkowski, Kathryn T ; De Rosa, Stephen C ; Dintwe, One ; Ginsberg, Ann ; Miner, Maurine D ; McElrath, M Juliana ; Tomaras, Georgia D ; Ruhwald, Morten ; DiazGranados, Carlos A ; Andersen-Nissen, Erica ; Seaton, Kelly E ; Middelkoop, Keren ; Williams, Anthony

BACKGROUND:

Tuberculosis (TB) remains the leading cause of infectious disease-related death. Recently, a trial of BCG revaccination and vaccination with H4:IC31, a recombinant protein vaccine, in South African adolescents (Aeras C-040-404) showed efficacy in preventing sustained QuantiFERON (QFT) conversion, a proxy for Mycobacterium tuberculosis (M.tb) infection. A phase 1b trial of 84 South African adolescents was conducted, concurrent with Aeras C-040-404, to assess the safety and immunogenicity of H4:IC31, H56:IC31 and BCG revaccination, and to identify and optimize immune assays for identification of candidate correlates of protection in efficacy trials.

METHODS:

Two doses of H4:IC31 and H56:IC31 vaccines were administered intramuscularly (IM) 56 days apart, and a single dose of BCG (2-8 × 10⁵ CFU) was administered intradermally (ID). T-cell and antibody responses were measured using intracellular cytokine staining and binding antibody assays, respectively. Binding antibodies and CD4+/CD8+ T-cell responses to H4- and H56-matched antigens were measured in samples from all participants. The study was designed to characterize safety and immunogenicity and was not powered for group comparisons. (Clinicaltrials.gov NCT02378207).

FINDINGS:

In total, 481 adolescents (mean age 13·9 years) were screened; 84 were enrolled (54% female). The vaccines were generally safe and well-tolerated, with no reported severe adverse events related to the study vaccines. H4:IC31 and H56:IC31 elicited CD4+ T cells recognizing vaccine-matched antigens and H4- and H56-specific IgG binding antibodies. The highest vaccine-induced CD4+ T-cell response rates were for those recognizing Ag85B in the H4:IC31 and H56:IC31 vaccinated groups. BCG revaccination elicited robust, polyfunctional BCG-specific CD4+ T cells, with no increase in H4- or H56-specific IgG binding antibodies. There were few antigen-specific CD8+ T-cell responses detected in any group.

INTERPRETATION:

BCG revaccination administered as a single dose ID and both H4:IC31 and H56:IC31 administered as 2 doses IM had acceptable safety profiles in healthy, QFT-negative, previously BCG-vaccinated adolescents. Characterization of the assays and the immunogenicity of these vaccines may help to identify valuable markers of protection for upcoming immune correlates analyses of C-040-404 and future TB vaccine efficacy trials.

FUNDING:

NIAID and Aeras.

项与 Tuberculosis vaccine H56IC(Statens Serum Institute) 相关的新闻（医药）

2023-02-21

·生物制品圈

新型疫苗佐剂研究进展

在新冠疫情背景下，公众对疫苗的认知度得到了极大的提升。作为疫苗的灵魂伴侣-佐剂，也从幕后走到了台前。佐剂在疫苗免疫机体产生抗体的过程中发挥着关键作用，其主要作用是辅助免疫应答及调节免疫反应。目前，佐剂的作用机制尚未完全研究清楚，且每个佐剂的作用也各不相同。按照佐剂的功能可将其大致分为三类，第一类佐剂具有储存、释放和靶向抗原作用，第二类佐剂具有免疫调节作用，第三类佐剂是兼具以上两种功能的佐剂。其中，铝佐剂的应用范围最为广泛，但会引起注射部位反应，诱导细胞免疫的能力较弱，不能冷冻活冻干，上述缺点在一定程度上限制了它的实际应用。表1 国内外使用铝佐剂的疫苗资料来源：申万宏源研究随着新型疫苗的不断涌现，对疫苗佐剂的要求越来越高。但疫苗佐剂的开发存在很高的技术壁垒，需要兼顾安全性和有效性，同时还要满足规模化生产需求，这些问题限制了新型佐剂的研发进展。二十多年来，FDA批准上市的新型佐剂仅有七款，分别为MF59、AS03、AS01、AS04、CpG 1018，以及新冠紧急使用的Matrix-M佐剂。表2 已获批上市的新型疫苗佐剂资料来源：《已上市人用预防疫苗佐剂的研究进展》，《获批上市疫苗中佐剂的研究进展》从全球研发趋势来看，新型疫苗佐剂向着Toll样受体激活剂、复合佐剂和纳米颗粒等多元化方向发展。Toll样受体（TLR）是天然免疫系统的重要成分，TLR受体激动剂被认为是一类非常有前途的疫苗佐剂。一系列研究证实，TLR4激动剂吡喃葡萄糖基脂质A（GLA-SE）作为H5N1流感疫苗佐剂[1]，在II期临床实验中免疫效果良好，并在结核疫苗[2]、肿瘤抗原疫苗[3]进行了测试。TLR7激动剂Imiquimod作为癌症疫苗佐剂用于头颈基底细胞癌[4]和黑色素瘤[5]的治疗，具有良好的耐受性和免疫原性。此外，TLR9激动剂MGN1703、IC31、SD-101也有望成为候选疫苗佐剂[6-8]。在复合佐剂领域，由磷脂、胆固醇和皂苷组成的复合物ISCOMATRIX能诱导广泛而有效的体液和细胞免疫应答，已在流感疫苗[9]、呼吸道合胞病毒[10]、生殖器疱疹病毒疫苗GEN-003[11]、新冠疫苗[12]等多款疫苗中开展临床研究。另有研究表明，由双链RNA类似物及TLR配体组成的Poly I:C/PIKA佐剂可显著提高狂犬疫苗在成人体内的抗体水平和T细胞反应[13]。近年来，纳米颗粒作为疫苗佐剂和递送系统也发展较快。例如，阳离子脂质体VCL-HB01在DNA登革热疫苗I期临床试验中表现出良好的安全性和耐受性[14]。使用纳米凝胶作为递送系统的肺炎链球菌疫苗[15]，在动物模型中经鼻内免疫，证明纳米凝胶装在的疫苗有效且安全。与此同时，国内也涌现出一批优秀企业，试图突破这一卡脖子领域。例如，瑞科生物对标葛兰素史克的AS01、AS03、AS04研发了三款新型佐剂，分别开展了针对带状疱疹疫苗、新冠疫苗、HPV疫苗的研发。迈科康生物自主研发的复合新型佐剂MA105佐剂系统，已被用于重组带状疱疹疫苗的研发。依生生物开发的皮卡佐剂已经在狂犬疫苗、乙肝疫苗上开展临床研究。此外，华泰诺、华普生物、沃森生物/上海泽润生物、智飞生物、三叶草生物也开始布局新型疫苗佐剂。随着对先天免疫信号通路的认知不断加深，更多潜在的新型疫苗佐剂会不断被发现。我们有理由相信，疫苗佐剂将迎来新的黄金时代。参考文献：1.Pillet S, et al. Humoral and cell-mediated immune responses to H5N1 plant-made virus-like particle vaccine are differentially impacted by alum and GLA-SE adjuvants in a phase 2 clinical trial. NPJ vaccines 2018;3(1):1-92.Penn-Nicholson A, et al. Safety and immunogenicity of the novel tuberculosis vaccine ID93+ GLASE in BCG-vaccinated healthy adults in South Africa: a randomised, double-blind, placebo-controlled phase 1 trial. Lancet Respir Med 2018;6(4):287-298.3.Bakos O, et al. Combining surgery and immunotherapy: turning an immunosuppressive effect into a therapeutic opportunity. J ImmuoTherapy of Cancer 2018; 6(1):1-11.4.Singh S, et al. Topical imiquimod as a neo-adjuvant chemotherapy for cartilage salvage in the treatment of nodular basal cell carcinomas of the head and neck. Indian Journal of Dermatology, Venereology and Leprology 2021;87(3):1-45.Meneveau MO，et al. Immunogenicity in humans of a transdermal multipeptide melanoma vaccine administered with or without a TLR7 agonist. J Immunother Cancer 2021; 9:e002214.6.Burghardt Wittig, et al. MGN1703, an immune-modulator and toll-like receptor 9 (TLR-9) agonist: From bench to bedside. Critical Reviews in Oncology/Hematology 2015; 94(1):31-44.7.Norrby M, et al. Safety and immunogenicity of the novel H4: IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: two phase I dose escalation trials. Vaccine 2017;35(12):1652-1661.8.Suliman S, et al. Dose optimization of H56: IC31 vaccine for tuberculosis-endemic populations. A double-blind, placebo-controlled, dose-selection trial. Am J Respir Crit Care Med 2019;199(2): 220-231.9.Windon RG，et al. Local immune responses to influenza antigen are synergistically enhanced by the adjuvant ISCOMATRIX. Vaccine 2002; 20: 490–497.10.Morelli A,et al. ISCOMATRIX adjuvant in the development of prophylactic and therapeutic vaccines. In:Immunopotentiators in modern vaccines. Elsevier; 2017. p. 311-332.11.Wagoner V, et al. Effects of Different Doses of GEN-003, a Therapeutic Vaccine for Genital Herpes Simplex Virus-2, on Viral Shedding and Lesions: Results of a Randomized Placebo-Controlled Trial. J Infec Diseases 2018; 12:1890-1899.12. Heath PT, et al.Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine. N ENGL J MED 2021; 385(13) :1172-1183.13. Kalimuddin S, et al. A phase II randomized study to determine the safety and immunogenicity of the novel PIKA rabies vaccine containing the PIKA adjuvant using an accelerated regimen. Vaccine 2017;35(51):7127-7132.14.Danko JR, et al. Safety and immunogenicity of a tetravalent dengue DNA vaccine administered with a cationic lipid-based adjuvant in a phase 1 clinical trial. Am J Trop Med Hyg 2018;98(3): 849-856.15. 杨雪华等. 纳米凝胶的研究进展[J]. 食品与药品, 2022年第2期, 183-187.

疫苗临床1期临床2期

100 项与 Tuberculosis vaccine H56IC(Statens Serum Institute) 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
肺结核	临床2期	南非	International AIDS Vaccine Initiative, Inc.	2019-01-31
肺结核	临床2期	坦桑尼亚	International AIDS Vaccine Initiative, Inc.	2019-01-31
结核	临床2期	南非	-	2019-01-27
潜伏性结核	临床2期	南非	Aeras Global TB Vaccine Foundation	2013-08-01
耐多药肺结核	临床1期	挪威	-	2015-11-01

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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


NCT02375698 (CTgov)	临床1期	肺结核	22	Placebo (Placebo)	鑰餘壓鏇夢觸範鏇網壓(觸網淵醖選網齋鏇積觸) = 網網積願簾鏇鑰選鹹鑰繭膚遞網遞壓製繭衊憲 (獵遞鏇願壓鹽衊壓鏇憲, 糧顧選蓋積窪鹹艱構築 ~ 衊顧醖鑰鹽淵壓壓鹹衊) 更多	-	2019-11-18
				H56:IC31 (Gr 1 H56:IC31 5/500)	簾蓋鹽繭獵鏇願餘構餘(鑰觸製蓋簾鏇選膚選糧) = 獵積鹹觸觸構獵範積獵顧鹽鏇膚觸蓋襯餘膚襯 (選鑰壓餘鏇壓遞糧鑰憲, 膚築遞鑰壓憲壓鬱製願 ~ 糧築醖膚觸構艱窪壓選) 更多
NCT02378207 (CTgov)	临床1期	结核	84	H4:IC31 (Group 1 H4:IC31)	選淵憲膚積遞構糧蓋網(願範繭壓齋範夢鹹構廠) = 餘遞顧餘鏇艱構艱壓蓋艱膚觸夢膚醖構積襯淵 (繭獵積壓構餘遞襯艱簾, 襯簾襯衊鬱壓鹹醖夢繭 ~ 範醖壓糧窪範鬱夢繭網) 更多	-	2019-11-18
				H56:IC31 (Group 2 H56:IC31)	選淵憲膚積遞構糧蓋網(願範繭壓齋範夢鹹構廠) = 獵願築艱蓋鏇鏇膚醖範艱膚觸夢膚醖構積襯淵 (繭獵積壓構餘遞襯艱簾, 窪鏇鏇蓋簾繭艱簾齋願 ~ 憲鹹獵鏇淵鏇選壓窪網) 更多
NCT01967134 (CTgov)	临床1期	潜伏性结核	25	H56:IC31 (H56:IC31 (50 ug H56) LTBI Neg)	願壓壓鑰遞艱選餘蓋醖(衊製鬱窪積蓋衊願積積) = 製衊積糧積膚顧衊鏇願憲齋醖繭觸顧夢鏇築齋 (顧願簾窪顧選積廠廠膚, 鹽衊範糧淵鹹窪齋夢簾 ~ 齋鏇積鏇憲壓繭積簾憲) 更多	-	2019-08-21
				H56:IC31 (H56:IC31 (15 ug H56) LTBI Pos)	願壓壓鑰遞艱選餘蓋醖(衊製鬱窪積蓋衊願積積) = 顧艱餘糧顧艱襯鹽艱鏇憲齋醖繭觸顧夢鏇築齋 (顧願簾窪顧選積廠廠膚, 糧構鹹範鏇鏇築築選鑰 ~ 築顧鏇簾構築積遞選願) 更多