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(由申请人提供)：这项R34拨款建议是计划一项临床试验，以测试两种钩虫候选疫苗抗原Na-GST-1和Na-APR-1(M74)可以对钩虫感染产生生物学影响的概念证明。这项试验将利用一种新的范例，通过在接种疫苗后用受控的实验性钩虫感染来挑战人类志愿者，以早期评估新的疫苗抗原。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，其中大多数是美洲钩虫。钩虫感染的临床特征是肠道失血引起的缺铁性贫血。Na-GST-1和Na-APR-1都是美洲按蚊采血途径的组成部分，在动物试验中基于它们的保护效果而被选择用于临床开发。临床开发计划是最终将这两种抗原结合成单一的双价疫苗产品。重组Na-GST-1和Na-APR-1(M74)都是在Alwater Gel(R)上配制的，在第一阶段试验中，已被证明对健康的成年人是安全的。在拟议的研究中，健康的钩虫幼虫成年志愿者将接种疫苗，然后用感染的美洲钩虫幼虫攻击他们，以评估接种疫苗对感染的影响，通过寄生虫学、免疫学和血液学参数进行评估。传统上，新型研究疫苗的概念验证是在流行地区的大型现场试验中进行的。这可能需要相当长的时间，这取决于研究对照组的感染发生率。R34提案的目标是计划一项研究，在该研究中，在钩虫新疫苗的临床开发早期进行概念验证测试，钩虫是最普遍和最重要的被忽视的热带病之一。这项试验的结果将允许在进行更大、更昂贵的第二和第三阶段试验之前，就进一步开发Na-GST-1和Na-APR-1(M74)钩虫疫苗做出关键的GO/NOGO决定。