Enhancement of immunogenicity by increased retention of antigenic proteins to injection sites and multimerization

通过疫苗预防传染病是减少许多细菌和病毒性疾病影响的最具成本效益的措施。疫苗的安全性是最重要的。因此，大多数人用新疫苗是作为灭活疫苗或组分疫苗开发的。基于蛋白质的组分疫苗的难点在于其免疫刺激性相对较弱。为了克服这个问题，测试了可能增强抗原刺激的各种佐剂。iProgen开发了一种新的技术，可以增强蛋白质在动物组织中的保留，并以最小的修饰使蛋白质多聚化。我们认为，增加抗原分子的保留和多聚化可能有助于通过与一些常用佐剂类似的机制来增强免疫刺激。拟议的研究是测试抗原蛋白的这种修饰是否有助于增强动物模型的免疫刺激。我们正在测试全身和粘膜刺激的潜力。我们将使用绿色荧光蛋白（GFP）作为测试抗原蛋白。iProgen开发的新技术对GFP进行了修饰，使其留在注射部位。在第一个实验中，将修饰的和未修饰的GFP肌肉内接种到小鼠，并监测针对GFP的特异性抗体的产生。传统的明矾佐剂是否协同作用也将被调查。在第二个实验中，在存在或不存在粘膜佐剂FSL-1的情况下，将修饰的和未修饰的GFP应用于鼻粘膜表面。将在接种小鼠的粪便和鼻洗液中监测粘膜表面特异性抗体的诱导。如果成功，这项技术将进一步测试修饰的病毒蛋白是否可以在动物模型中诱导对病毒疾病的保护性免疫。最终，我们希望这项技术能帮助开发出更安全，更有效，更便宜的疫苗来治疗各种传染病。

Protection from infectious diseases by vaccines is the most cost effective measure to decrease the impact ofmany bacterial and viral diseases. For vaccines their safety is the paramount importance. Thus, most newvaccines for human use are developed as inactivated or component vaccines. The difficulty in the protein-basedcomponent vaccines is their relatively weak immunological stimulation. To overcome this problem variousadjuvants that potentially enhance the antigenic stimulation are tested. iProgen has developed new technologiesthat enhance the retention of proteins to animal tissues and multimerize proteins with minimal modification.We thought the increased retention and multimerization of antigenic molecules might help enhance theimmune stimulation through the similar mechanism as some of the commonly used adjuvant.The proposed study is to test if such modifications of an antigenic protein may help enhance the immunestimulation in animal models. We are testing the potentials in both systemic and mucosal stimulations. We willuse Green Fluorescent Protein (GFP) as the test antigenic protein. GFP is modified to stay in the injected siteby the new technology developed by iProgen. In the first experiment the modified and unmodified GFPs willbe inoculated to mice intramuscularly and the development of specific antibody to GFP is monitored. Whetherconventional alum adjuvant co-operatively works or not will also be investigated. In the second experiment themodified and unmodified GFP will be applied to nasal mucosal surface in the presence or absence of a mucosaladjuvant, FSL-1. The induction of specific antibodies on the mucosal surface will be monitored in feces andnasal wash of the inoculated mice. If successful, this technology would be further tested whether modified viralproteins can induce protective immunity to viral diseases in animal models. Ultimately, we are hoping thistechnology will help develop new safer, more efficacious and less expensive vaccines for various infectiousdiseases.