This trial will investigate the administration of two new tuberculosis vaccines, called AERAS-402 and MVA85A. The purpose of this trial is to assess what happens when both of these vaccines are given one after the other. The trial will assess the safety of both vaccines and also their ability to stimulate an immune response within the body. It is hoped that when these two vaccines are given in sequence, the combined immune response is even better than when each vaccine is used individually.

开始日期2012-09-01

申办/合作机构

University of Oxford

[+4]

NCT01378312 / Completed临床1期

A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS-402 When Administered to HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection

This Phase I study will be conducted as a randomized, double-blind, placebo-controlled study in healthy adult subjects who are HIV-negative, BCG-vaccinated, and have no evidence of tuberculosis infection. The study will be conducted at one clinical research site in India.
The available live tuberculosis vaccine, Bacillus Calmette-Guérin (BCG), provides incomplete protection against pulmonary tuberculosis. For unknown reasons, a BCG revaccination or "booster", while not toxic, does not provide much additional protection. AERAS-402 presents tuberculosis antigens in the setting of a new, live, replication-deficient adenovirus vaccine that may increase T cell-mediated immunity and thus protection from tuberculosis. Since BCG-vaccinated individuals are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to individuals already vaccinated with BCG.

开始日期2011-02-01

申办/合作机构

Aeras Global TB Vaccine Foundation

NCT01198366 / Completed临床1/2期

A Phase II, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Immunogenicity of AERAS-402 in BCG-vaccinated, HIV-uninfected Infants Without Evidence of Tuberculosis

AERAS-402 will be given to infants of at least 16 weeks of age who have already been vaccinated with BCG to determine if AERAS-402 will increase protection of infants to tuberculosis.

开始日期2010-09-01

申办/合作机构

Aeras Global TB Vaccine Foundation

100 项与 Tuberculosis vaccine(Aeras Technologies LLC) 相关的临床结果

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100 项与 Tuberculosis vaccine(Aeras Technologies LLC) 相关的专利（医药）

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451

项与 Tuberculosis vaccine(Aeras Technologies LLC) 相关的文献（医药）

2023-10-18·International immunopharmacology

Construction and evaluation of a novel multi-antigenic Mycobacterium tuberculosis subunit vaccine candidate BfrB-GrpE/DPC.

Article

作者: Hongxia Niu ; Qianqian Cao ; Tingting Zhang ; Yunjie Du ; Pu He ; Lei Jiao ; Bingxiang Wang ; Bingdong Zhu ; Lina Hu ; Ying Zhang

Tuberculosis poses a significant threat to human health due to the lack of an effective vaccine. Although promising progress has been made in the development of tuberculosis vaccines, new vaccines that broaden the antigenic repertoire need to be developed to eradicate this illness. In this study, we used Mycobacterium tuberculosis ferritin BfrB and heat-shock protein GrpE to construct a novel multi-antigenic fusion protein, BfrB-GrpE (BG). BG protein was stably overexpressed in the soluble form in Escherichia coli at a high yield and purified via sequential salt fractionation and hydrophobic chromatography. Purified BG was emulsified in an adjuvant containing N, N'-dimethyl-N, N'-dioctadecylammonium bromide, polyinosinic-polycytidylic acid, and cholesterol (DPC) to construct the BG/DPC vaccine, which stimulated strong cellular and humoral immune responses in mice. Moreover, combination of BG with our previously developed vaccine, Mtb10.4-HspX (MH), containing antigens from both the proliferating and dormant stages, significantly reduced the bacterial counts in the lungs and spleens of M. tuberculosis-infected mice. Importantly, mice that received BG + MH/DPC after M. tuberculosis H37Rv infection survived slightly better (100% survival) than those that received the BCG vaccine (80% survival), although the difference was not statistically significant. Our findings can aid in the selection of antigens and optimization of vaccination regimens to improve the efficacy of tuberculosis vaccines.

2023-09-27·medRxiv : the preprint server for health sciences

The potential health and economic impacts of new tuberculosis vaccines under varying delivery strategies in Delhi and Gujarat, India: a modelling study.

作者: Rebecca A Clark ; Allison Portnoy ; Chathika K Weerasuriya ; Tom Sumner ; Roel Bakker ; Rebecca C Harris ; Kirankumar Rade ; Sanjay Kumar Mattoo ; Dheeraj Tumu ; Nicolas A Menzies ; Richard G White

Background:

India has the largest tuberculosis burden globally, but this burden varies nationwide. All-age tuberculosis prevalence in 2021 ranged from 747/100,000 in Delhi to 137/100,000 in Gujarat. Previous modelling has demonstrated the benefits and costs of introducing novel tuberculosis vaccines in India overall. However, no studies have compared the potential impact of tuberculosis vaccines in regions within India with differing tuberculosis disease and infection prevalence. We used mathematical modelling to investigate how the health and economic impact of two potential tuberculosis vaccines, M72/AS01 _E and BCG-revaccination, could differ in Delhi and Gujarat under varying delivery strategies.

Methods:

We applied a compartmental tuberculosis model separately for Delhi (higher disease and infection prevalence) and Gujarat (lower disease and infection prevalence), and projected epidemiological trends to 2050 assuming no new vaccine introduction. We simulated M72/AS01 _E and BCG-revaccination scenarios varying target ages and vaccine characteristics. We estimated cumulative cases, deaths, and disability-adjusted life years averted between 2025-2050 compared to the no-new-vaccine scenario and compared incremental cost-effectiveness ratios to three cost-effectiveness thresholds.

Results:

M72/AS01 _E averted a higher proportion of tuberculosis cases than BCG-revaccination in both regions (Delhi: 16.0% vs 8.3%, Gujarat: 8.5% vs 5.1%) and had higher vaccination costs (Delhi: USD$118 million vs USD$27 million, Gujarat: US$366 million vs US$97 million). M72/AS01 _E in Delhi could be cost-effective, or even cost-saving, for all modelled vaccine characteristics. M72/AS01 _E could be cost-effective in Gujarat, unless efficacy was assumed only for those with current infection at vaccination. BCG-revaccination could be cost-effective, or cost-saving, in both regions for all modelled vaccine scenarios.

Discussion:

M72/AS01 _E and BCG-revaccination could be impactful and cost-effective in Delhi and Gujarat. Differences in impact, costs, and cost-effectiveness between vaccines and regions, were determined partly by differences in disease and infection prevalence, and demography. Age-specific regional estimates of infection prevalence could help to inform delivery strategies for vaccines that may only be effective in people with a particular infection status. Evidence on the mechanism of effect of M72/AS01 _E and its effectiveness in uninfected individuals, which were important drivers of impact and cost-effectiveness, particularly in Gujarat, are also key to improve estimates of population-level impact.

2023-09-01·Nature communications

Addressing mechanism bias in model-based impact forecasts of new tuberculosis vaccines.

Article

作者: M Tovar ; Y Moreno ; J Sanz

In tuberculosis (TB) vaccine development, multiple factors hinder the design and interpretation of the clinical trials used to estimate vaccine efficacy. The complex transmission chain of TB includes multiple routes to disease, making it hard to link the vaccine efficacy observed in a trial to specific protective mechanisms. Here, we present a Bayesian framework to evaluate the compatibility of different vaccine descriptions with clinical trial outcomes, unlocking impact forecasting from vaccines whose specific mechanisms of action are unknown. Applying our method to the analysis of the M72/AS01_E vaccine trial -conducted on IGRA+ individuals- as a case study, we found that most plausible models for this vaccine needed to include protection against, at least, two over the three possible routes to active TB classically considered in the literature: namely, primary TB, latent TB reactivation and TB upon re-infection. Gathering new data regarding the impact of TB vaccines in various epidemiological settings would be instrumental to improve our model estimates of the underlying mechanisms.

项与 Tuberculosis vaccine(Aeras Technologies LLC) 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

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研发状态

适应症	最高研发状态	国家/地区	公司
肺结核	临床2期	-	National Institutes of Health 更多

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分期

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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


NCT02414828 (CTgov)	临床2期	肺结核	72	Placebo (Placebo)	(糧鬱鹹鬱淵蓋獵簾餘鏇) = 壓鏇簾窪壓製簾夢網獵廠築鏇憲繭簾遞廠蓋積 (觸積壓鹽簾簾製膚顧網, 餘壓窪製夢製廠蓋願鏇 ~ 艱鏇餘蓋鹹艱蓋醖築願) 更多	-	2016-05-04
				AERAS-402 3 x 10^8 vp (AERAS-402 3 x 10^8 vp)	(糧鬱鹹鬱淵蓋獵簾餘鏇) = 壓蓋鑰醖顧選築顧糧鬱廠築鏇憲繭簾遞廠蓋積 (觸積壓鹽簾簾製膚顧網, 壓膚淵鹹壓窪獵願構壓 ~ 艱夢蓋襯襯範觸範艱蓋) 更多
NCT01017536 (CTgov)	临床2期	结核 \| HIV感染	26	Placebo (Placebo)	(齋鬱齋憲製觸鬱窪窪糧) = 齋遞糧壓遞膚構艱觸糧淵窪觸範膚積網鏇鹽遞 (繭製繭夢糧顧艱構憲衊, 齋構範簾鏇積鏇淵蓋網 ~ 夢構夢範醖選襯遞衊簾) 更多	-	2014-10-13
				AERAS-402 (Investigational Vaccine)	(齋鬱齋憲製觸鬱窪窪糧) = 憲膚顧願簾糧選製築壓淵窪觸範膚積網鏇鹽遞 (繭製繭夢糧顧艱構憲衊, 窪範衊鬱糧醖製膚鹹鬱 ~ 醖鑰膚顧鏇齋顧餘壓願) 更多
NCT01198366 (CTgov)	临床1/2期	结核	487	placebo (Dose Finding - Group 1)	(窪繭獵構襯築襯壓遞構) = 憲膚餘願鏇簾窪衊簾醖淵齋網積範簾鑰簾鹽餘 (鏇鹹憲選淵膚衊繭夢淵, 鹽襯繭製憲艱醖願觸顧 ~ 製蓋繭繭襯膚鹹鏇鏇鑰) 更多	-	2015-08-04
				AERAS-402 (Dose Finding - Group 2)	(窪繭獵構襯築襯壓遞構) = 蓋簾鬱網壓範蓋壓艱遞淵齋網積範簾鑰簾鹽餘 (鏇鹹憲選淵膚衊繭夢淵, 艱齋觸繭膚糧膚淵製淵 ~ 艱製獵淵廠獵簾夢憲鹽) 更多