Outcomes of the Interactions of Flaviviruses with Antibo

黄病毒与抗体相互作用的结果

• 批准号: 7196738
• 负责人: THEODORE C PIERSON
• 金额: --
• 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/7196738
• 关键词: Flaviviridae; West Nile virus; active immunization; biotechnology; dengue; dengue virus; emerging infectious disease; enzyme linked immunosorbent assay; flow cytometry; hemorrhagic fever; host organism interaction; humoral immunity; immune response; neutralizing antibody; nucleic acid sequence; polymerase chain reaction; protein binding; tissue /cell culture; vaccine development; vaccine evaluation; viral vaccines; virion; virus envelope; virus protein; western blottings

Flaviviruses are a group of positive stranded RNA viruses that have a global impact due to their widespread distribution and ability to cause disease in humans and economically important domesticated animals. Several members of this group, such as dengue virus (DEN) and West Nile virus (WNV), are considered emerging or re-emerging pathogens because the incidence with which they encounter humans and cause disease is increasing each year at an alarming rate. Thus, there an urgent need exists for the development and implementation of safe and efficacious vaccines. The envelope proteins present on the surface of flavivirus virions are the primary targets for the humoral (antibody-mediated) immune response during natural infection. Thus, the generation of antibodies capable of binding to this array of viral proteins and blocking infection is a critical aspect of the immune response, and an important goal of vaccine development. However, under some circumstances, the presence of antibodies can also increase the efficiency of viral infection. Importantly, this antibody-dependent enhancement (ADE) of infection has been linked to a more severe clinical outcome of DEN infection (Dengue hemorrhagic fever; DHF). The possibility that immunization may elicit antibodies capable of enhancing infection poses a significant challenge for the development of a DEN vaccine, and highlights the importance of understanding not only the magnitude, but also the breadth, specificity, and persistence of humoral immunity following vaccination. In this regard, we are investigating the mechanisms of antibody-mediated neutralization and ADE with the goal of understanding the biochemical and cellular factors that determine the outcome of the interaction of flavivirus particles with antibody.

黄病毒是一组正链RNA病毒，由于其广泛分布和在人类和经济上重要的驯养动物中引起疾病的能力而具有全球影响。该组的几个成员，如登革病毒（DEN）和西尼罗河病毒（WNV），被认为是新兴或重新出现的病原体，因为它们遇到人类并引起疾病的发病率每年以惊人的速度增加。因此，迫切需要开发和实施安全有效的疫苗。存在于黄病毒病毒粒子表面上的包膜蛋白是自然感染期间体液（抗体介导的）免疫应答的主要靶标。因此，产生能够结合这种病毒蛋白并阻断感染的抗体是免疫应答的关键方面，也是疫苗开发的重要目标。然而，在某些情况下，抗体的存在也可以增加病毒感染的效率。重要的是，这种感染的抗体依赖性增强（ADE）与DEN感染（登革出血热; DHF）的更严重临床结果有关。免疫接种可能引发能够增强感染的抗体的可能性对DEN疫苗的开发提出了重大挑战，并强调了理解接种疫苗后体液免疫的重要性，不仅是幅度，而且是广度，特异性和持久性。在这方面，我们正在研究抗体介导的中和和ADE的机制，目的是了解决定黄病毒颗粒与抗体相互作用结果的生化和细胞因素。