Preclinical Development of a Recombinant Dengue Vaccine

重组登革热疫苗的临床前开发

• 批准号: 6868106
• 负责人: Carolyn Louise Weeks-Levy
• 金额: $ 91.37万
• 依托单位: HAWAII BIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6868106
• 关键词: Macaca mulatta; biotechnology; cooperative study; dengue; dengue virus; disease /disorder model; drug screening /evaluation; immunoaffinity chromatography; immunologic substance development /preparation; immunomodulators; laboratory mouse; laboratory rabbit; microorganism disease chemotherapy; monoclonal antibody; protein purification; vaccine development; vector vaccine; viral vaccines; virus antigen; virus protein

DESCRIPTION (provided by applicant): Dengue viruses (category A pathogen) are estimated to infect 100 million people annually and are considered to cause one of the most important arthropod-borne viral diseases in terms of human morbidity and mortality. Although 40% of the world's population can benefit from a dengue vaccine, there is no clear pathway to commercialization of such a vaccine. Barriers to commitment of the necessary funds to drive commercialization derive from scientific, market, medical and investment-funding uncertainties that, added together, create unacceptable risk for today's companies. Dengue and dengue hemorrhagic fever are caused by one of four closely related virus serotypes. Infection with one of the serotypes does not provide cross-protective immunity from the other serotypes and is believed to exacerbate the disease upon infection with a second serotype. To date, no dengue vaccine has been licensed and human clinical trials of several dengue vaccine candidates have not demonstrated durable immunity against all four dengue serotypes. Hawaii Biotech, Inc. has developed a multicomponent, recombinant subunit dengue vaccine that has the potential to elicit long-lasting immunity to all four dengue serotypes. The vaccine will be developed for phase I clinical trials to be performed in collaboration with The Walter Reed Army Institute of Research. The vast majority of the preclinical development work outlined in this proposal will be performed under Good Manufacturing Practice (cGMP) and Good Laboratory Practice (GLP). The preclinical development work encompasses scale-up and cGMP manufacture of recombinant dengue antigens covering the four dengue serotypes, purification of the antigens, testing and release of the vaccine prior to use in humans, toxicology testing of the vaccine in animal models, fill/finish of the vaccine active pharmaceutical ingredient (API) and adjuvant API and preparation of an Investigational New Drug Application.

描述（由申请人提供）：登革热病毒（A 类病原体）估计每年感染 1 亿人，被认为是导致人类发病率和死亡率最重要的节肢动物传播病毒性疾病之一。尽管世界上40%的人口可以从登革热疫苗中受益，但这种疫苗的商业化还没有明确的途径。推动商业化所需资金投入的障碍源于科学、市场、医疗和投资融资的不确定性，这些不确定性加在一起，给当今的公司带来了不可接受的风险。登革热和登革出血热是由四种密切相关的病毒血清型之一引起的。其中一种血清型的感染不会提供针对其他血清型的交叉保护性免疫，并且据信在感染第二种血清型时会加剧疾病。迄今为止，还没有登革热疫苗获得许可，并且几种登革热候选疫苗的人体临床试验尚未证明对所有四种登革热血清型具有持久免疫力。 Hawaii Biotech, Inc. 开发了一种多组分重组亚基登革热疫苗，有可能对所有四种登革热血清型产生持久免疫力。该疫苗将与沃尔特·里德陆军研究所合作进行第一阶段临床试验。本提案中概述的绝大多数临床前开发工作将根据良好生产规范 (cGMP) 和良好实验室规范 (GLP) 进行。临床前开发工作包括涵盖四种登革热血清型的重组登革热抗原的放大和 cGMP 生产、抗原纯化、疫苗在人体使用前的测试和释放、疫苗在动物模型中的毒理学测试、填充/完成疫苗活性药物成分 (API) 和佐剂 API 的制备以及研究性新药申请的准备。

项目成果

Preclinical and clinical development of a dengue recombinant subunit vaccine.

登革热重组亚单位疫苗的临床前和临床开发。

• 发表时间: 2015-12-10
• 影响因子: 5.5
• 作者: Manoff, Susan B;George, Sarah L;Bett, Andrew J;Yelmene, Michele L;Dhanasekaran, Govindarajan;Eggemeyer, Linda;Sausser, Michele L;Dubey, Sheri A;Casimiro, Danilo R;Clements, David E;Martyak, Timothy;Pai, Vidya;Parks, D Elliot;Coller, Beth
• 通讯作者: Coller, Beth