Clinical and translational evaluation of vector saliva based vaccination strategies for Zika and other important or emerging vector-borne diseases

针对寨卡病毒和其他重要或新出现的媒介传播疾病的基于媒介唾液的疫苗接种策略的临床和转化评估

• 批准号: 10014248
• 负责人: Matthew Memoli
• 金额: $ 105.85万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10014248
• 关键词: 5 year old; Agreement; Arboviruses; Area; Award; Bite; Caribbean region; Central America; Cessation of life; Child; Clinical; Clinical Research; Clinical Trials; Collaborations; Cooperative Research and Development Agreement; Culicidae; Data; Dengue; Disease; Disease Outbreaks; Endemic Diseases; Enrollment; Evaluation; Exposure to; Follow-Up Studies; Funding; Goals; Grant; Human; Immune response; Immune system; Individual; Japanese encephalitis virus; Leishmania; Leishmaniasis; Longevity; Malaria; Manuscripts; Maryland; Methods; Morbidity - disease rate; Mosquito Control; Mosquito-borne infectious disease; National Institute of Allergy and Infectious Disease; Parasitic Diseases; Phase; Phlebotominae; Prophylactic treatment; Proteins; Protocols documentation; Protozoa; Publishing; Rift Valley Fever; Saliva; Salivary; South America; Testing; Time; United States National Institutes of Health; Universities; Update; Vaccination; Vaccines; Vector-transmitted infectious disease; Virus; West Nile virus; Work; Yellow Fever; Zika Virus; arbovirus disease; base; bench to bedside; chikungunya; clinical development; disease transmission; feeding; follow-up; immunoregulation; mortality; novel; novel vaccines; phase 1 study; prevent; response; translational study; vaccination strategy; vector; vector control

Mosquito-borne diseases continue to cause significant morbidity and mortality worldwide despite on-going control efforts. In 2015, there were >200 million cases of malaria worldwide, causing nearly half a million deaths, with most of the deaths occurring among children under the age of 5 years. Mosquitoes also transmit arboviruses, including dengue, yellow fever, West Nile virus, chikungunya, Rift Valley fever, Japanese encephalitis, and Zika virus. The recent outbreak of Zika virus in Central and South America, as well as the Caribbean, serves as a reminder of how quickly these viruses can spread and how difficult they can be to control. We completed a Phase I study of a novel universal mosquito-borne disease vaccine and are now preparing a manuscript. Through modulation of the immune system after a mosquito feeding, this vaccine targets the vector saliva and may provide prophylaxis against multiple arboviral and protozoal diseases. In addition the vaccine potentially leads to a reduced mosquito lifespan after feeding therefore also reducing transmission of these diseases. This protocol marks the first time a vaccine targeting mosquito saliva has been tested in humans and the first time clean mosquito feedings on humans have been performed in the NIH Clinical Center. As a continuation of our close collaboration with LMVR we were awarded an NIH Bench To Bedside award and in the past year have completed enrollment of a follow up clinical study in the NIH Clinical Center to evaluate the effect on the immune response of multiple exposures to the same vector. This study included the evaluation of two species of mosquito as well as sandflies, the vector of leishmania. We expect the final data from this study to be instrumental in further understanding how vaccination strategies that target vector saliva may work in individuals from endemic disease areas. We expect to complete the analysis during the next year. During the next year we will complete a third clinical trial, a follow up study to our initial study of AGS-v with an updated version of the vaccine AGS-v Plus. This Phase Ib study will be completed in collaboration with LMVR and University of Maryland under a CRADA agreement. We have initiated the study and expect to fully enroll in the next 6-8 months. This study should continue the clinical development of this unique vaccine strategy we initiated in 2018.

尽管正在进行控制努力，但蚊子传播的疾病继续在全世界造成严重的发病率和死亡率。 2015年，全球有超过2亿例疟疾病例，造成近50万人死亡，其中大部分死亡发生在5岁以下的儿童中。 蚊子也传播虫媒病毒，包括登革热、黄热病、西尼罗河病毒、基孔肯雅热、裂谷热、日本脑炎和寨卡病毒。 最近在中美洲和南美洲以及加勒比地区爆发的寨卡病毒提醒人们，这些病毒传播的速度有多快，控制起来有多困难。 我们完成了一项新的通用蚊媒疾病疫苗的I期研究，现在正在准备手稿。 通过在蚊子进食后调节免疫系统，该疫苗靶向载体唾液，并可提供对多种虫媒病毒和原生动物疾病的预防。 此外，疫苗可能导致蚊子在喂食后寿命缩短，因此也减少了这些疾病的传播。 该方案标志着第一次在人类中测试针对蚊子唾液的疫苗，以及第一次在NIH临床中心对人类进行清洁的蚊子喂养。 作为我们与LMVR密切合作的延续，我们被授予NIH Bench To Bedside奖，并在过去一年中完成了NIH临床中心的后续临床研究招募，以评估多次暴露于同一载体对免疫应答的影响。 这项研究包括两种蚊子以及白蛉，利什曼原虫的载体的评价。 我们希望这项研究的最终数据有助于进一步了解靶向载体唾液的疫苗接种策略如何在地方病地区的个体中发挥作用。 我们预计在明年完成分析。 在接下来的一年里，我们将完成第三次临床试验，这是我们对AGS-v的初步研究的后续研究，其中包括疫苗AGS-v Plus的更新版本。 根据CRADA协议，本Ib期研究将与LMVR和马里兰州大学合作完成。 我们已经启动了这项研究，预计将在未来6-8个月内完成招募。 这项研究应该继续我们在2018年启动的这种独特疫苗策略的临床开发。