Evaluation Studies of a Dengue-2 DNA Vaccine in Monkeys

猴子登革热 2 DNA 疫苗的评价研究

• 批准号: 6779943
• 负责人: IDALI MARTINEZ-MARTINEZ
• 金额: $ 26.08万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6779943
• 关键词: Macaca mulatta; active immunization; cell mediated lymphocytolysis test; dengue virus; enzyme linked immunosorbent assay; glycolates; immunity; lactates; vaccine development; vaccine evaluation; vector vaccine; viral vaccines; virus envelope

DESCRIPTION (provided by applicant): Dengue fever and dengue hemorrhagic fever result from the infection with any of the four serotypes of dengue (DEN) viruses. These diseases have become a global public health problem, affecting 100 million people anually. Moreover, DEN viruses are potential bioterrorism agents since neither an effective treatment nor vaccine is available. Thus, research is needed to develop an effective and safe vaccine that will prevent infection and disease caused by any of these viruses. The objective of this study is to develop a DNA vaccine capable of inducing protective immune responses in rhesus macaques against DEN-2 virus infection. Our long-term objective is to develop a tetravalent DEN DNA vaccine. Our vaccine strategy is focused on the dengue envelope because this protein mediates the early binding and entry steps of infection. Neutralizing antibodies (Nab) against this protein were shown to be protective against pathogenic virus infection and disease. In this study we plan to evaluate immune responses generated in monkeys by our DNA vaccine candidate, Vec-D2 which encodes prM and env proteins of DEN-2, using four different vaccination regimens. Monkeys will be immunized with Vec-D2 either alone or absorbed onto polylactide-co-glycolide (PLG) microparticles, followed by the administration of an inactivated DEN-2 virus boost adjuvanted in MF59 or MF59 alone. Our hypothesis is that immune responses induced by Vec-D2 will be enhanced by coupling the plasmid DNA to PLG and that these responses could be further boosted by administration of inactivated virus in MF59. Immune responses will be monitored by ELISA, virus neutralization, CTL and proliferation assays. The level of protection induced by the different vaccine strategies against DEN-2 virus infection will be also ascertained: Complete protection will be determined by the absence of detectable viremia and of anamnestic immune responses. Results obtained from these studies will provide important information for the design and development of DNA vaccines expressing the envelope protein of DEN-l, DEN -3 and DEN-4.

描述（由申请人提供）：登革热和登革热出血热是由登革热（DEN）病毒的四种血清型中的任何一种感染引起的。这些疾病已成为全球公共卫生问题，造成1亿人的影响。此外，由于没有有效的治疗和疫苗，DEN病毒是潜在的生物恐怖剂。因此，需要进行研究以开发有效且安全的疫苗，以防止这些病毒中的任何一种引起的感染和疾病。这项研究的目的是开发一种DNA疫苗，能够在恒河猴中诱导防止DEN-2病毒感染的保护性免疫反应。我们的长期目标是开发四位含量DEN DNA疫苗。 我们的疫苗策略集中在登革热膜上，因为该蛋白质介导了感染的早期结合和进入步骤。针对该蛋白质的中和抗体（NAB）被证明是针对致病病毒感染和疾病的保护性。在这项研究中，我们计划使用四种不同的疫苗接种方案来评估我们的DNA疫苗候选者VEC-D2在猴子中产生的免疫反应，该疫苗VEC-D2编码DEN-2的PRM和ENV蛋白。猴子将单独使用VEC-D2免疫，或吸收到多乳酸 - 糖苷（PLG）微粒上，然后在MF59或MF59中施用灭活的DEN-2病毒增强佐剂。我们的假设是，通过将质粒DNA与PLG耦合，通过VEC-D2诱导的免疫反应将增强，并且通过在MF59中施用灭活病毒，可以进一步提高这些反应。免疫反应将通过ELISA，病毒中和，CTL和增殖测定法监测。还将确定由不同的疫苗策略对DEN-2病毒感染引起的保护水平：将通过缺乏可检测的病毒血症和吞噬免疫反应来确定完全保护。从这些研究中获得的结果将为表达DEN-L，DEN-3和DEN-4的包膜蛋白的DNA疫苗的设计和开发提供重要信息。