A Vaccine for Schistosomiasis, "SchistoShield"

血吸虫病疫苗“SchistoShield”

• 批准号: 10341126
• 负责人: DARRICK Albert CARTER
• 金额: $ 50.65万
• 依托单位: PAI LIFE SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10341126
• 关键词: Address; Adjuvant; Africa; Antibody titer measurement; Antigens; Antiparasitic Agents; Back; Biological Assay; Burkina Faso; Cells; Certification; Chemistry; Clinical Trials; Country; Coupling; Cyclic GMP; Data; Development; Disease; Dose; Drug Stability; Drug resistance; Emulsions; Ensure; Environment; European Union; Excretory function; Exhibits; Fermentation; Freeze Drying; Funding; Future; Geography; Goals; Grant; Granuloma; Human; Immune; Immunization; Infection; Injections; Intestines; Larva; Licensure; Life; Life Cycle Stages; Lipids; Liver diseases; Madagascar; Methods; Mus; National Institute of Allergy and Infectious Disease; Oryctolagus cuniculus; Papio; Parasites; Parasitic Diseases; Pathology; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase II Clinical Trials; Phase II/III Clinical Trial; Phase III Clinical Trials; Phase Ib Trial; Praziquantel; Preparation; Procedures; Proteins; Regulation; Research; Research Design; Research Project Grants; Risk; Rodent; Safety; Schistosoma hematobium infection; Schistosomiasis; Secure; Serious Adverse Event; Shipping; Ships; Site; Small Business Innovation Research Grant; Testing; Time; Tissues; Toxicology; Treatment Efficacy; United States National Institutes of Health; Vaccination; Vaccine Antigen; Vaccines; base; clinical development; clinical research site; cost effective; disease transmission; egg; exhaustion; fight against; first-in-human; global health; immune function; meetings; pre-clinical; programs; prophylactic; transmission process; vaccine candidate; vaccine development

PROJECT SUMMARY Schistosomiasis is a major parasitic disease which could impact up to a billion people in 74 countries. Current control strategies rely primarily on anti-parasitic drugs alone (praziquantel) which has proven inadequate due to both reinfection and the inherent threat of drug resistance. We have developed a potent schistosomiasis vaccine, termed SchistoShield®, targeting a functionally important antigen (Sm-p80) formulated with a potent immune- stimulator (GLA-SE). SchistoShield® has been exhaustively tested in rodents, rabbits, and baboons and has exhibited protection at all parasitic life-cycle stages including larvae, worms, and egg laying, survival, and excretion. We are completing our Phase II SBIR grant research focused on manufacture, lyophilization, and fill/finish of the antigen and will be entering into three clinical trials (first an NIH funded Phase 1 human trial in the USA, and next two Phase 1b trials funded by the European union which will be performed in Burkina Faso and Madagascar in Africa) beginning in the first quarter of 2020. To support our upcoming trials, this Phase IIb grant will focus on studies required to ensure stability of the vaccine drug product (DP) for the duration of the trials as required by regulatory agencies. The research will include assessing long-term stability, formal shipping studies, and development of a sensitive potency assay suitable for later stage clinical development. The potency assay will include immunization into mice followed by antibody titers after a single injection. We will forcibly degrade our antigen using simulated real-life conditions and test the altered protein for retention of immunological function using our potency assay. The goal will be to identify which quality parameters are directly indicative of a loss of potency. At the end of these studies we will have our DP on stability, formal shipping methods identified, a sensitive potency assay developed, and have identified critical quality parameters of potency of the vaccine. All these studies are required in preparation for Phase 2 and 3 clinical trials and future licensure and deployment.

项目摘要 血吸虫病是一种主要的寄生疾病，可能会影响74个国家的十亿人群。当前的 控制策略仅依靠仅抗寄生虫药物（praziquantel），这证明由于 再感染和继承耐药性的威胁。我们已经开发了一种有效的血吸虫病疫苗， 称为Schistoshield®，针对具有有效免疫的功能重要抗原（SM-P80） 刺激器（GLA-SE）。 Schistoshield®已在啮齿动物，兔子和狒狒中进行了详尽的测试，并具有 在所有寄生生命周期的裸露保护 排泄。我们正在完成II期SBIR赠款研究，重点是制造，冻干和 抗原的填充/饰面，将进行三项临床试验（首先是NIH资助的1期人类试验 美国以及由欧洲联盟资助的下两阶段1B试验将在布基纳法索进行 和非洲的马达加斯加）从2020年第一季度开始。 为了支持我们即将举行的试验，此阶段IIB赠款将重点放在确保疫苗稳定性所需的研究上 根据监管机构要求的试验期间，药物产品（DP）。研究将包括 评估长期稳定性，正式运输研究以及适合于 后期临床发展。效力评估将包括对小鼠的免疫抑制，然后进行抗体 一次注射后的滴度。我们将使用模拟的现实生活条件强行降低抗原，并测试 使用我们的效力测定法改变了蛋白质以保留免疫功能。目标是确定哪个 质量参数直接表明效力损失。 在这些研究结束时，我们将拥有有关稳定性，正式运输方法的DP 效力测定开发，并确定了疫苗效力的关键质量参数。所有这些 需要进行研究，以准备第2阶段和3阶段的临床试验以及未来的许可和部署。

项目成果

Cross-species prophylactic efficacy of Sm-p80-based vaccine and intracellular localization of Sm-p80/Sm-p80 ortholog proteins during development in Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium.

• DOI: 10.1007/s00436-017-5634-4
• 发表时间: 2017-11
• 期刊: Parasitology research
• 影响因子: 2
• 作者: Molehin AJ;Sennoune SR;Zhang W;Rojo JU;Siddiqui AJ;Herrera KA;Johnson L;Sudduth J;May J;Siddiqui AA
• 通讯作者: Siddiqui AA

Longevity of Sm-p80-specific antibody responses following vaccination with Sm-p80 vaccine in mice and baboons and transplacental transfer of Sm-p80-specific antibodies in a baboon.

在小鼠和狒狒中接种 Sm-p80 疫苗以及在狒狒中进行 Sm-p80 特异性抗体经胎盘转移后，Sm-p80 特异性抗体反应的寿命。

• DOI: 10.1007/s00436-014-3879-8
• 发表时间: 2014
• 期刊: Parasitology research
• 影响因子: 2
• 作者: Zhang,Weidong;Ahmad,Gul;Le,Loc;Rojo,JuanU;Karmakar,Souvik;Tillery,KoryA;Torben,Workineh;Damian,RaymondT;Wolf,RomanF;White,GaryL;Carey,DavidW;Carter,Darrick;Reed,StevenG;Siddiqui,AfzalA
• 通讯作者: Siddiqui,AfzalA

Translational Activities to Enable NTD Vaccines.

促进 NTD 疫苗的转化活动。

• DOI: 10.1016/bs.pmbts.2016.05.004
• 发表时间: 2016
• 期刊: Progress in molecular biology and translational science
• 作者: Gray,SA;Coler,RN;Carter,D;Siddiqui,AA
• 通讯作者: Siddiqui,AA

Sm-p80-based schistosomiasis vaccine: double-blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission-blocking efficacy.

• DOI: 10.1111/nyas.13942
• 发表时间: 2018-08
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Zhang W;Molehin AJ;Rojo JU;Sudduth J;Ganapathy PK;Kim E;Siddiqui AJ;Freeborn J;Sennoune SR;May J;Lazarus S;Nguyen C;Redman WK;Ahmad G;Torben W;Karmakar S;Le L;Kottapalli KR;Kottapalli P;Wolf RF;Papin JF;Carey D;Gray SA;Bergthold JD;Damian RT;Mayer BT;Marks F;Reed SG;Carter D;Siddiqui AA
• 通讯作者: Siddiqui AA

Schistosoma mansoni antigen Sm-p80: prophylactic efficacy using TLR4 agonist vaccine adjuvant glucopyranosyl lipid A-Alum in murine and non-human primate models.

• DOI: 10.1136/jim-2018-000786
• 发表时间: 2018-12
• 期刊: Journal of investigative medicine : the official publication of the American Federation for Clinical Research
• 作者: Zhang W;Ahmad G;Molehin AJ;Torben W;Le L;Kim E;Lazarus S;Siddiqui AJ;Carter D;Siddiqui AA
• 通讯作者: Siddiqui AA