Rational Anthrax Vaccine with Structural Epitopes on VLP

描述（由申请人提供）：现有的炭疽疫苗AVA会引起严重的副作用，需要多次免疫接种，当面临炭疽生物恐怖主义威胁时，无法进行预防性疫苗预防。尽管重组炭疽保护性抗原（PA）免疫可以提供相当程度的抗感染保护，但基于PA的候选疫苗使用未批准用于人类的佐剂。我们建议设计和开发下一代重组炭疽疫苗与内在的佐剂能力，基于自组装病毒样颗粒（VLP）的表面上的PA表位的多个介绍。由于PA蛋白和B型肝炎核心颗粒（HBc）--最主要的VLP载体的最近解决的高分辨率结构，设计PA-VLP嵌合疫苗的合理方法现在是可能的。在PA蛋白的功能和免疫原性描述方面也有实质性进展。我们将联合收割机结合先进的分子建模，以确保折叠和组装功能性VLP与最佳PA表位展示。这项可行性研究是一项平台工作，将使这种方法合法化，同时提供有效的疫苗。无毒、无感染性的重组PA-HBc嵌合蛋白将进一步开发为疫苗。成功的PA-HBc设计将为将炭疽毒力的其他组分纳入VLP疫苗制剂提供基础技术，而不会影响安全性或生产成本。

DESCRIPTION (provided by applicant): The existing anthrax vaccine, AVA, causes serious side effects and requires multiple immunizations, precluding preventive vaccine prophylaxis when faced with an anthrax bioterrorist threat. Though recombinant anthrax protective antigen (PA) immunity may provide a substantial level of protection against infection, PA-based vaccine candidates utilize adjuvants not approved for human use. We propose to design and develop next generation recombinant anthrax vaccines with intrinsic adjuvant capabilities, based on multiple presentation of PA epitopes on the surface of self-assembling virus-like particles (VLP). A rational approach to designing PA-VLP chimeric vaccines is now possible due to the recently solved high-resolution structures of both PA protein and hepatitis B core (HBc) particle-the most prominent VLP carrier. There is also substantial progress in functional and immunogenic descriptions of the PA protein. We will combine this knowledge with advanced molecular modeling to ensure folding and assembly of functional VLP with optimal PA epitope display. This feasibility study is a platform work which will legitimize the approach while providing an effective vaccine. Nontoxic and non-infectious recombinant PA-HBc chimeric protein will be further developed as a vaccine. Successful PA-HBc design would provide a basis technology for inclusion of other components of anthrax virulence into the VLP vaccine formulation without compromising safety or production cost.