ACT 7-IMMUNE RESPONSE & OUTCOME OF SEQUENTIAL FLAVIVIRUS INFECTIONS MOUSE MODEL

行动 7-免疫反应

• 批准号: 7959199
• 负责人: IDALI MARTINEZ-MARTINEZ
• 金额: $ 14.65万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959199
• 关键词: Active Immunization; Animals; Antigens; Biological Assay; Birds; Blood; Brain; Clinical; Computer Retrieval of Information on Scientific Projects Database; Country; DNA Vaccines; Dengue; Dengue Virus; Encephalitis; Equus caballus; Fever; Flavivirus Infections; Funding; Future; Grant; Human; Immune; Immune response; Indirect Fluorescent Antibody Technique; Individual; Infection; Institution; Kinetics; Measures; Monitor; Monkeys; Morbidity - disease rate; Mouse Strains; Mus; Neutralization Tests; Outcome; Passive Immunization; Play; Predisposition; Reporting; Research; Research Personnel; Resources; Role; Serum; Source; South America; Symptoms; System; Testing; United States; United States National Institutes of Health; Vaccines; Viral Load result; Viral Proteins; Virus; Virus Diseases; West Indies; West Nile virus; cross reactivity; cytokine; design; epizootic; improved; mortality; mouse model; multidisciplinary; pathogen; programs; research study; transmission process; vaccine candidate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. West Nile (WNV) is an emerging virus that was introduced in the United States on 1999 and has expanded rapidly throughout the country. This virus caused more than 12,000 reported human cases in the last two years with clinical symptoms that ranged from a mild febrile illness to a potentially fatal encephalitis. Little is known about WNV transmission in dengue-endemic regions, such as Central and South America and the Caribbean islands. Epizootic studies demonstrated that the virus is circulating in horses, birds and probably humans but symptomatic WN cases have not yet been reported in these countries. Since there is extensive cross reactivity between DEN and WNV antigens, our hypothesis is that individuals that are immune to dengue viruses (DENV) may be cross-protected against WNV illnesses. To prove this hypothesis, we will perform animal studies using Balb/c mice. We will first evaluate the susceptibility and kinetics of WNV infection in this mice strain (specific aim 1). Then, two separate experiments will be performed to test if cross-protection against WNV can be achieved by active immunization with DENV or a DEN-2 DNA vaccine candidate (specific aim 2) or passive immunization with human serum collected from primary or secondary DENV infections (specific aim 3). Immune responses against DENV and WNV will be measured by indirect immunofluorescence assays, neutralization tests and cytokine assays using the Bio-plex system. Mice morbidity and mortality after WNV challenge will be monitored for 28 days and viral loads in blood and brain will be determined by Taqman assays. If cross-protection is achieved, these experiments will allow us to determine the type and duration of the immune responses that may correlate with protection. Future studies will be aimed to determine the DEN viral proteins that may play an important role in cross-protection. Results from this and future studies in monkeys will provide valuable information to improve the design of broad spectrum vaccines that could potentially protect against both pathogens, DENV and WNV.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 西尼罗河（WNV）是一种新兴病毒，于1999年在美国引入，在全国范围内迅速扩展。在过去两年中，该病毒引起了12,000多例人类病例，其临床症状范围从轻度的发热疾病到潜在的致命性脑炎。关于登革热地区的WNV传播知之甚少，例如中美洲和南美以及加勒比海群岛。 Epizootic的研究表明，该病毒在马，鸟类和可能的人类中循环，但在这些国家尚未报告有症状的WN病例。由于DEN和WNV抗原之间存在广泛的交叉反应性，因此我们的假设是免疫登革热病毒（DENV）的个体可以针对WNV疾病进行交叉保护。为了证明这一假设，我们将使用BALB/C小鼠进行动物研究。我们将首先评估这种小鼠菌株中WNV感染的敏感性和动力学（特定的目标1）。然后，将进行两个单独的实验，以测试是否可以通过用DENV或DEN-2 DNA候选疫苗的主动免疫来实现针对WNV的交叉保护（特定AIM 2）或用从原发性或继发性DENV感染收集的人血清的被动免疫（特定AIM 3）。对DENV和WNV的免疫反应将通过使用Bio-Plex系统间接免疫荧光测定，中和测试和细胞因子测定法测量。 WNV挑战后的小鼠发病率和死亡率将受到28天的监测，血液和大脑的病毒负荷将由Taqman分析确定。如果实现了交叉保护，这些实验将使我们能够确定可能与保护相关的免疫反应的类型和持续时间。未来的研究将旨在确定可能在跨保护中起重要作用的DEN病毒蛋白。从猴子进行的这项研究和未来研究的结果将提供有价值的信息，以改善有可能保护病原体，DENV和WNV的广泛疫苗的设计。