Planning for Experimental Infection Trial to Test Hookworm Vaccine Efficacy

 描述（由申请人提供）：该R34资助提案旨在计划一项临床试验，该试验将测试两种候选钩虫疫苗抗原Na-GST-1和Na-APR-1（M74）对钩虫感染的生物学影响的概念验证。本试验将利用一种新的模式，通过在接种疫苗后用对照实验钩虫感染挑战人类志愿者，对新疫苗抗原进行早期评估。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导致的缺铁性贫血。Na-GST-1和Na-APR-1都是N.根据它们在动物试验中的保护功效，选择americanus和用于临床开发。临床开发计划是最终将两种抗原联合收割机组合成单一的二价疫苗产品。重组Na-GST-1和Na-APR-1（M74），都是在Alhydrogel（r）上配制的，在1期试验中被证明对健康成人是安全的。在拟议的研究中，健康的钩虫初治成年志愿者将接种疫苗，然后用感染性N.美洲大蠊幼虫，以评估疫苗接种对感染的影响，如通过寄生虫学、免疫学和血液学参数评估的。传统上，新型研究疫苗的概念验证是在流行地区的大型田间试验中进行的。这些可能需要相当长的时间，具体取决于研究对照组的感染发生率。这项R34提案的目的是计划一项研究，在钩虫新疫苗的临床开发早期对概念验证进行测试，钩虫是被忽视的热带病中最流行和最重要的疾病之一。这项试验的结果将允许在进行更大，更昂贵的2期和3期试验之前，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。

 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.