Optimizing the formulation of a protein based smallpox vaccine

优化基于蛋白质的天花疫苗的配方

• 批准号: 8056790
• 负责人: Stuart N. Isaacs
• 金额: $ 49.07万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8056790
• 关键词: Adjuvant; Adverse effects; Africa; Area; Bioterrorism; Collaborations; Development; Discipline; Drug Formulations; Environment; Event; FDA approved; Funding Mechanisms; Future Generations; GPA33 gene; HIV Infections; Homologous Gene; Homologous Protein; Immune response; Immunosuppression; Industry; Kansas; Life; Modeling; Monkeypox; Mus; National Institute of Allergy and Infectious Disease; Population; Population Heterogeneity; Process; Protein C; Proteins; Research; Research Institute; Research Personnel; Smallpox; Smallpox Vaccine; Smallpox Viruses; Vaccine Adjuvant; Vaccines; Vaccinia virus; Viral Proteins; base; biodefense; nonhuman primate; response

DESCRIPTION (provided by applicant): This proposal, in response to RFA AI-07-003, is for the development of a future generation smallpox vaccine that can be safely administered to a diverse population. We have made great strides in the proof-of-principle selection of appropriate protein targets and the initial formulation of a protein-based smallpox vaccine. However, in order to bring the vaccine to the next level, optimization of the vaccine formulation and further improvements of the vaccine are required. To accomplish this, we bring together investigators with different areas of expertise and develop collaborations between academic researchers from different disciplines and with industry. Our hypothesis is that a protein-based smallpox vaccine can more safely elicit a protective response in a broad range of recipients than the current FDA approved live smallpox vaccine. While we have shown that this approach is feasible, there are a number of steps that are needed to bring this approach to the next level. The majority of our prior development of a protein-based smallpox vaccine has been with Vaccinia virus proteins, which based on their high homology to variola virus proteins, could confer cross protection against smallpox. There is theoretical and experimental evidence that variola proteins may ultimately be better candidates to generate protection against smallpox and therefore we will produce the variola virus homologs of A33, B5, and L1. Additionally, the formulation of the proteins with adjuvant needs to be optimized. An iterative and sequential process is now required to bring the vaccine to the next level. To accomplish this we will: Aim 1. Produce the variola virus protein homologs of Vaccinia virus A33, B5, and L1 proteins (C-PERL) Aim 2. Optimize the protein/adjuvant vaccine formulation (U. Kansas) Aim 3. Evaluate, in a "checkerboard" fashion, the ability of the optimized vaccine formulation to generate immune responses and protect from Vaccinia virus challenge in mice (U. Penn) Aim 4. Examine immune responses and protection from monkeypox challenge in a non-human primate model (Southern Research Institute)

描述（由申请人提供）：该提案响应RFA AI-07-003，用于开发未来一代的天花疫苗，可以安全地管理对多样化的人群。我们在原则选择适当的蛋白质靶标和基于蛋白质的天花疫苗的初始配方方面取得了长足的进步。但是，为了将疫苗提升到一个新的水平，需要优化疫苗配方并进一步改善疫苗。为了实现这一目标，我们将具有不同专业知识领域的调查员聚集在一起，并在不同学科和行业的学术研究人员之间进行合作。我们的假设是，基于蛋白质的天花疫苗比当前批准的活节天花疫苗更安全地在广泛的受体中更安全地引起保护性反应。虽然我们已经证明这种方法是可行的，但是将这种方法提升到一个新的水平需要许多步骤。我们先前对基于蛋白质的天花疫苗的开发大部分是使用离谷酵母蛋白的，该蛋白质基于它们与Variola病毒蛋白的高同源性，可以允许对天花进行交叉保护。有理论和实验证据表明，水虫蛋白最终可能是更好的候选者来产生对天花的保护，因此我们将产生A33，B5和L1的Variola病毒同源物。另外，需要优化具有辅助的蛋白质的配方。现在需要进行迭代和顺序过程才能将疫苗提升到一个新的水平。为此，我们将：目标1。生产疫苗病毒A33，B5和L1蛋白（C-Perl）的Variola病毒蛋白蛋白质同源物（C-Perl）目标2。优化蛋白质/辅助疫苗配方（U. Kansas）目标3。 （U. Penn）目标4。在非人类灵长类动物模型（南部研究所）中检查免疫反应和保护免受Monkeypox挑战的保护