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疾病影响的最具成本效益的措施。对于疫苗来说，其安全性是最重要的。因此，大多数人用新疫苗都是作为灭活疫苗或成分疫苗开发的。蛋白质成分疫苗的难点在于其免疫刺激相对较弱。为了克服这个问题，我们测试了各种可能增强抗原刺激的佐剂。iProgen开发了新技术，增强了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。我们认为增加抗原分子的保留和多聚可能有助于增强免疫刺激，通过类似的机制，一些常用的佐剂。这项研究的目的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，使其停留在注射部位。在第一个实验中，将修饰的和未修饰的GFP接种于小鼠肌内，并监测GFP特异性抗体的产生。此外，还将对传统明矾佐剂是否具有协同作用进行研究。在第二个实验中，在有无粘膜佐剂FSL-1的情况下，将改良的和未改良的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，这项技术将在动物模型中进一步测试修饰的病毒蛋白是否能诱导对病毒性疾病的保护性免疫。最终，我们希望这项技术将有助于开发新的更安全、更有效、更便宜的疫苗，用于治疗各种传染病。

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.