Planning for Experimental Infection Trial to Test Hookworm Vaccine Efficacy

规划实验性感染试验以测试钩虫疫苗功效

• 批准号: 8926594
• 负责人: David Joseph Diemert
• 金额: $ 16.1万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8926594
• 关键词: Adult; Aftercare; Agonist; Albendazole; Alhydrogel; Anemia; Animals; Antibody Response; Antigens; Applications Grants; Area; Biological; Blood; Brazil; Case Report Form; Child; Clinical; Clinical Protocols; Clinical Trials; Clinical Trials Data Monitoring Committees; Consent Forms; DNA; Decision Making; Development; Development Plans; Documentation; Dose; Double-Blind Method; Endoscopy; Good Clinical Practice; Grant; Heme; Hemorrhage; Hookworm Infections; Hookworms; Human; Human Subject Research; Human Volunteers; Immunohistochemistry; Immunologics; Incidence; Infection; Infection Control; Injection of therapeutic agent; Intestines; Investigational New Drug Application; Iron deficiency anemia; Larva; Life; Lipid A; Manuals; Mass Spectrum Analysis; Measures; Medical; Microscopy; Modeling; Monitor; Necator; Necator americanus; Parasites; Parasitic infection; Pathway interactions; Pharmacy facility; Phase; Phase I Clinical Trials; Phase II/III Trial; Placebo Control; Placebos; Procedures; Protocols documentation; Recombinants; Risk; Safety; Safety Management; Saline; Sample Size; Sampling; Serum; Source; Staging; Testing; Time; United States; Universities; Vaccinated; Vaccination; Vaccine Antigen; Vaccines; antigen challenge; arm; base; capsule; data management; design; egg; feeding; innovation; neglected tropical diseases; novel; novel vaccines; operation; protective efficacy; public health relevance; toll-like receptor 4; tool; vaccine candidate; vaccine development; vaccine efficacy; volunteer; zinc protoporphyrin

 DESCRIPTION (provided by applicant): This R34 grant proposal is to plan a clinical trial that will test the proof-of-concept that two candidate hookworm vaccine antigens, Na-GST-1 and Na-APR-1 (M74), can have a biological impact on hookworm infection. This trial will utilize a new paradigm for early assessment of new vaccine antigens by challenging human volunteers with a controlled experimental hookworm infection after vaccination. Hookworm is one of the most important parasitic infections, with over 500 million people infected worldwide, most with the Necator americanus species. The clinical hallmark of hookworm infection is iron deficiency anemia resulting from intestinal blood loss. Both Na-GST-1 and Na-APR-1 are components of the blood-feeding pathway of N. americanus and were selected for clinical development based on their protective efficacy in animal trials. The clinical development plan is to eventually combine the two antigens into a single, bivalent vaccine product. Recombinant Na-GST-1 and Na-APR-1 (M74), both formulated on Alhydrogel(r), have been shown to be safe when administered to healthy adults in Phase 1 trials. In the proposed study, healthy hookworm-naïve adult volunteers will be vaccinated followed by challenging them with infective N. americanus larvae to assess the effect of vaccination on infection, as assessed by parasitologic, immunologic and hematologic parameters. Traditionally, proof-of-concept for novel investigational vaccines is tested in large field trials in endemic areas. These can take considerable time depending on the incidence of infection in the control arm of the study. The objective of this R34 proposal is to plan a study in which proof-of-concept is tested early in the clinical development of new vaccines for hookworm, one of the most prevalent and important of the Neglected Tropical Diseases. The results of this trial will permit critical Go/NoGo decisions to be made on further development of the Na-GST-1 and Na-APR-1 (M74) hookworm vaccine, prior to conducting larger, more costly Phase 2 and 3 trials.

 描述（由应用程序提供）：该R34赠款提案是计划一项临床试验，该试验将测试概念验证的证明，即两种候选钩虫疫苗抗原Na-GST-1和NA-APR-1（M74）可以对钩虫感染产生生物学影响。该试验将利用一种新的范式来提早评估新的疫苗抗原，通过对疫苗后受控的实验钩虫感染来挑战人类志愿者。钩虫是最重要的寄生虫感染之一，全世界有超过5亿人感染了超过5亿人，其中大多数是杀虫剂的美国物种。钩虫感染的临床标志是肠失血引起的铁缺乏贫血。 NA-GST-1和NA-APR-1都是美国乳杆菌的血液喂养途径的组成部分，并根据其在动物试验中的保护有效性而被选为临床发育。临床开发计划最终将两种抗原结合成单一的二价疫苗产品。重组Na-GST-1和Na-APR-1（M74），均在Alhydrogel（R）上配制，在1阶段试验中对健康成年人施用时，已证明是安全的。在拟议的研究中，将接种疫苗的健康钩虫志愿者，然后用感染性n. amenterus幼虫来挑战他们，以评估疫苗对感染的影响，如寄生虫，免疫学和血液学参数评估。传统上，新型研究疫苗的概念概念在内在地区的大型野外试验中进行了测试。根据研究控制部门的感染事件，这些时间可能需要相当长的时间。该R34提案的目的是计划一项研究，在该研究中，概念证明是在钩虫新疫苗的临床开发中进行测试的，这是被忽视的热带疾病中最普遍和最重要的。该试验的结果将允许对NA-GST-1和NA-APR-1（M74）钩虫疫苗的进一步开发做出关键的GO/NOGO决策，然后进行更大，昂贵的第2阶段和3阶段试验。