Schistosome Vaccines

血吸虫疫苗

基本信息

批准号：
8503696
负责人：
Jonathan D. Kurtis
金额：
$ 35.32万
依托单位：
RHODE ISLAND HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-10 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8503696
关键词：
Adult Aftercare Age Animal Model Antibodies Antibody Formation Antigens Area Bioinformatics Buffaloes Cattle Chronic Complementary DNA Coupled Data Development Enrollment Exons Expression Library Falciparum Malaria Funding Health Human Hypersensitivity Hypersensitivity skin testing IgE Immune Immune response Immunity Individual Libraries Life Measures Mediating Methods Morbidity - disease rate Outcome Study Parasites Performance Phage Display Phase II Clinical Trials Philippines Plasma Platyhelminths Praziquantel Process Proteome Publishing Reliance Resistance Rodent Rodent Model Safety Sampling Schistosoma Schistosoma japonicum Schistosomiasis Schistosomiasis japonica Serological Signal Transduction Socioeconomic Status Staging Time Tissues Vaccine Antigen Vaccines Water base candidate validation chemotherapy cohort cytokine disability efficacy testing egg epidemiologic data follow-up health economics mortality novel novel vaccines preclinical efficacy preclinical safety public health relevance research study response safety testing screening sex vaccine candidate vaccine development vaccine efficacy volunteer

项目摘要

DESCRIPTION (provided by applicant): The overall aim of this R01 resubmission is to develop vaccines against human schistosomiasis japonica. Schistosomiasis, caused by three principle species of dioecious trematodes (flatworms), currently infects over 250 million people world-wide and results in 1.53 million DALYs lost per annum. A recent reassessment of the global burden of schistosomiasis suggests that the actual health burden is 4 to 30 times greater than the previous WHO estimate. These tremendous figures underscore the impact a schistosomiasis vaccine would have on global human health. Although schistosomiasis is effectively treated with Praziquantel (PZQ), rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. We propose to capitalize on plasma samples and parasitologic data already collected during our previous R-01 funded studies, to identify novel antigens associated with resistance in humans. We will use a whole proteome, differential screening method to identify parasite antigens that are recognized by antibodies in plasma of resistant but not susceptible individuals. We will validate these candidates using high throughput immune profiling of antibody responses and analysis of these responses in the context of resistance to reinfection. We will extend the validation of these candidates by assessment of cellular immune responses in a newly enrolled cohort of S. japonicum infected individuals living in an endemic area of Leyte, the Philippines. Finally, candidates will be down-selected by bioinformatics, tissue- and stage- specific immunolocalization studies, and skin testing for hypersensitivity in S. japonicum infected buffalo. Four of these down-selected candidates will be evaluated for efficacy and safety (including hypersensitivity) in buffalo vaccine trials in Yrs 4 and 5. The outcome of these studies will be a list of validated antigens associated with resistance to reinfection in humans. These data will provide a strong basis to prioritize antigenic targets for additional preclinical safety and efficacy studies in both rodents and large animal models. These data will further the rational development of vaccines that limit reinfection and consequent morbidity and mortality in humans.

描述（由申请人提供）：该R01重新提交的总体目的是开发针对人类血吸虫病Japonica的疫苗。血吸虫病是由三种主要的雌雄同体的杂种（Flatworms）引起的，目前在全球范围内感染了超过2.5亿的人，每年损失153万达利。最近对全球血吸虫病负担的重新评估表明，实际的健康负担比以前的估计值高4至30倍。这些巨大的数字强调了血吸虫病疫苗对全球人类健康的影响。尽管血吸虫病有效地用Praziquantel（PZQ）治疗，但仅基于化学疗法的反弹发病率就可以快速再感染有效控制，并证明了当前为这些寄生虫开发疫苗的努力。我们建议利用在先前的R-01资助研究中已经收集的血浆样本和寄生虫数据，以识别与人类耐药性相关的新型抗原。我们将使用一种全蛋白质组的差异筛选方法来识别寄生虫抗原，这些抗原被抗性但不易感个体的血浆中的抗体识别。我们将使用抗体反应的高通量免疫分析验证这些候选物，并在抵抗重新感染的背景下对这些反应进行分析。我们将通过评估居住在菲律宾Leyte的地方性地区的新纳波省感染链球菌感染的人群中的细胞免疫反应来扩展这些候选者的验证。最后，候选人将通过生物信息学，组织和特定的免疫定位研究和皮肤测试对japonicum链球菌感染的水牛进行超敏反应。这些下降的候选者中有四个将在YRS 4和5中评估在水牛疫苗试验中的功效和安全性（包括超敏反应）。这些研究的结果将是与在人类中耐药性相关的有效抗原的经过验证的抗原列表。这些数据将为在啮齿动物和大型动物模型中的其他临床前安全性和功效研究中优先考虑抗原靶标的优先级基础。这些数据将进一步发展疫苗的合理发展，这些疫苗限制了人类的恢复以及随之而来的发病率和死亡率。