Development of a Recombinant Subunit Ebola Vaccine

描述（由申请人提供）：埃博拉病毒和马尔堡病毒是丝状病毒科的唯一成员，可引起出血热，在高达90%的人类病例中是致命的。目前还没有疫苗或抗病毒疗法来预防或治疗丝状病毒感染。由于其特殊的致命性和武器化的潜力，这些病毒已被确定为生物盾计划和NIAID生物防御研究议程中的关键生物防御目标。夏威夷生物技术公司成功生产了几种重组埃博拉病毒蛋白，这些蛋白在小鼠中显示出很强的免疫原性和保护作用。该项目的具体目标是扩大候选疫苗的抗原库，以诱导对埃博拉和马尔堡病毒的广泛保护，确认疫苗配方在豚鼠和非人灵长类动物模型中的保护功效，并为临床前二期开发做好准备。挑战研究将代表该方法概念的临床前证明，而纳入额外的糖蛋白将确保候选疫苗诱导针对最致病性丝状病毒株的广泛保护性免疫。该候选疫苗有潜力单独使用或与NIAID疫苗研究中心目前正在开发的其他候选疫苗联合使用。一种利用重组亚基蛋白的安全有效的疫苗将满足该国生物防御准备战略的重要需求。

DESCRIPTION (provided by applicant): Ebola and Marburg viruses, the only members of the family Filoviridae, cause hemorrhagic fevers which are lethal in up to 90% of human cases. No vaccine or antiviral therapy currently exists to prevent or treat Filovirus infection. Due to their exceptional lethality and potential for weaponization, these viruses have been identified as key biodefense targets in both Project Bioshield and the NIAID Biodefense Research agenda. Hawaii Biotech, Inc. has successfully produced several recombinant Ebola virus proteins which show strong immunogenicity and protective efficacy in mice. The specific goals of this project are to expand the antigenic repertoire of the vaccine candidate to induce broad protection against both Ebola and Marburg viruses, to confirm the protective efficacy of the vaccine formulations in guinea pig and non-human primate models, and to ready the product for preclinical development in Phase II. The challenge studies will represent the preclinical proof of concept for the approach, while the inclusion of additional glycoproteins will ensure that the vaccine candidate induces broad protective immunity against the most pathogenic Filovirus strains. The vaccine candidate has potential as a stand alone or as a partner in a prime-boost approach in combination with other vaccine candidates currently being developed by the NIAID Vaccine Research Center. A safe and efficacious vaccine utilizing recombinant subunit proteins would fill an important need in the country's biodefense preparedness strategy.