Development of sG as a human vaccine against Nipah/Hendra

开发 sG 作为针对尼帕/亨德拉的人类疫苗

• 批准号: 8463115
• 负责人: Antony S. Dimitrov
• 金额: $ 99.07万
• 依托单位: PROFECTUS BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8463115
• 关键词: Adjuvant; Adverse event; Aerosols; Agonist; Animal Model; Animals; Antigens; Area; Australia; Bangladesh; Biological; Biological Assay; Biological Products; Categories; Cell Line; Centers for Disease Control and Prevention (U.S.); Cercopithecus pygerythrus; Cessation of life; Characteristics; Clinical; Clinical Research; Clinical Trials; Consult; Cyclic GMP; Data; Development; Disease; Disease Outbreaks; Dose; Drug Formulations; Encephalitis; Environment; Equus caballus; Evaluation; Family; Fatality rate; Felis catus; Ferrets; Frequencies; Funding; Future; Hendra Virus; Henipavirus; Human; Immune response; Immunization; Immunology; India; Infection; Laboratories; Lead; Livestock; Lung diseases; Malaysia; Mammals; Marketing; Modeling; Morbidity - disease rate; Nipah Virus; Oryctolagus cuniculus; Outcome; Paramyxoviridae; Paramyxovirus; Persons; Phase; Preclinical Testing; Preparation; Process; Production; Proteins; Public Health; Qualifying; RNA Viruses; Reagent; Recombinants; Reporting; Research; Safety; Seeds; Specific qualifier value; Subunit Vaccines; Testing; Therapeutic; Toxicology; Tropism; United States National Institutes of Health; Vaccination; Vaccines; Viral; Virus; Virus Diseases; Zoonoses; aluminum sulfate; animal efficacy; attachment protein G; base; biothreat; cell bank; clinical lot; design; glycoprotein G; immunogenicity; improved; meetings; mortality; nonhuman primate; prevent; product development; prophylactic; research clinical testing; research study; transmission process

DESCRIPTION (provided by applicant): Nipah virus (NiV) and Hendra virus (HeV) are closely related viral zoonoses that form the genus Henipavirus in the family Paramyxoviridae. They are enveloped, negative-sense RNA viruses that cause a systemic and fatal disease in a variety of animal hosts and in humans. In some outbreaks, the death toll has reached as high as 75%. They are classified as biological safety level-4 (BSL4) viruses and possess several characteristics that justify their listing as Category C biothreat agents by the NIH and CDC including the ability to be transmitted via aerosol. There is currently no approved vaccine or therapeutic against either NiV or HeV. Annual outbreaks of NiV human infections in Bangladesh and other areas justify the benefit of a prophylactic vaccine for improving public health as well as reducing their potential as a biothreat. Immunization and challenge studies performed in cats, ferrets, and nonhuman primates using recombinant HeV soluble attachment protein G, HeV-sG, have demonstrated that a HeV-sG subunit vaccine can be completely effective against both HeV and NiV. In fact, HeV-sG subunit is currently being evaluated in Australia as an equine vaccine. Our objective here is to produce 1 gram of HeV-sG that will be suitable to perform IND-supportive toxicology and efficacy studies as necessary steps to support the evaluation of HeV-sG as a human vaccine against NiV and HeV. We will do so through the following specific aims: 1) Optimize HeV-sG immunogen/adjuvant formulation; 2) Identify release assays for HeV-sG; 3) Manufacture 1 g of HeV-sG; 4) Perform IND supportive animal studies. By the end of the funding period, we will have (i) identified an adjuvant suitable for further clinical development; ii) prepared a characterized research-grade "pre-seed" for use to manufacture a HeV-sG Master Cell Bank; (iii) optimized a development-scale process suitable for the manufacturing of cGMP clinical trial materials under future proposals; (iv) manufactured at least 1 g of development-grade vaccine to perform IND supportive toxicology and efficacy studies, and (v) executed said animal studies. Subsequent applications will pursue cGMP manufacture of 1) a master cell bank and 2) clinical lots of HeV-sG vaccine for Phase 1 clinical evaluation.

描述（由申请人提供）：Nipah病毒（NIV）和Hendra病毒（HEV）是密切相关的病毒人畜共患病，在paramyxoviridae家族中形成了HENIPAVIRUS属。它们是包裹的，负性的RNA病毒，在各种动物宿主和人类中引起全身性疾病。在某些暴发中，死亡人数高达75％。它们被归类为生物安全级别-4（BSL4）病毒，并具有多种特征，这些特征通过NIH和CDC证明其列表为C类生物治疗剂，包括通过Aerosol传播的能力。目前尚无针对NIV或HEV的批准疫苗或治疗性。孟加拉国和其他地区的NIV人类感染的年度暴发证明了预防性疫苗的好处，以改善公共卫生，并降低其作为生物治疗的潜力。使用重组HEV可溶性附着蛋白G，HEV-SG在猫，雪貂和非人类灵长类动物中进行的免疫和挑战研究表明，HEV-SG亚基疫苗可以完全有效地针对HEV和NIV。实际上，HEV-SG亚基目前正在澳大利亚评估为马疫苗。我们的目的是生产1克HEV-SG，适合于对NIV和HEV评估HEV-SG作为人类疫苗评估的必要步骤，以对NIV和HEV进行评估。我们将通过以下特定目的这样做：1）优化HEV-SG免疫原/辅助配方； 2）确定HEV-SG的释放测定； 3）制造1克HEV-SG； 4）进行IND支持性动物研究。到资金期结束时，我们将（i）确定适合进一步临床开发的辅助； ii）准备了一个特征的研究级“预种植”，用于制造HEV-SG大细胞库； （iii）优化了适用于未来建议下的CGMP临床试验材料制造的开发规模的过程； （iv）生产至少1 g开发级疫苗以进行IND支持性毒理学和功效研究，以及（v）执行的动物研究。随后的应用将追求CGMP生产1）主细胞库和2）用于1期临床评估的HEV-SG疫苗的临床大量。