IMMUNOGENICITY TESTING OF A FULLY SYNTHETIC SUBUNIT VACCINE AGAINST INFLUENZA

全合成流感亚单位疫苗的免疫原性测试

• 批准号: 7477190
• 负责人: CATHERINE H CHARLES
• 金额: $ 29.99万
• 依托单位: MEDIVAS, LLC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7477190
• 关键词: Achievement; Amides; Animals; Antibody Formation; Antigens; Biological Assay; Clinical Immunology; Clinical Trials; Condition; Coupling; Data; Development; Dose; Drug Formulations; Esters; Future; Government; Grant; Hemagglutinin; Human; Immune response; Immune system; Influenza; Influenza A Virus, H5N1 Subtype; Locales; Measures; Methods; Mus; Nucleoproteins; Peptides; Polymers; Population; Principal Investigator; Proteins; Purpose; Range; Route; Safety; Schedule; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Solutions; Subunit Vaccines; Synthetic Vaccines; T-Lymphocyte; Technology; Testing; Treatment Protocols; Vaccination; Vaccines; Variant; Viral; Viral Antigens; Virulent; base; biodegradable polymer; commercialization; concept; cost; dosage; human disease; immunogenicity; influenza virus vaccine; influenzavirus; novel vaccines; pandemic disease; poly(ethylacrylate); polypeptide; programs; research study; response; subcutaneous; vaccine evaluation

DESCRIPTION (provided by applicant): A formidable challenge confronting clinical immunology is the development of synthetic vaccines that could offer advantages over traditional methods in safety, reliability and cost. Appropriate delivery of protein and peptide antigens to the immune system has proved to be a major technical hurdle. The search for tractable solutions to this problem has received significant impetus in recent years by the development of biodegradable polymers as delivery vehicles. In this grant, we introduce poly(ester amide) co-polymers as a valuable addition to the current armory of suitable delivery polymers and present supportive initial proof-of-concept experiments that demonstrate the use of these polymers as a component of a protective vaccine for influenza. Specifically, these polymer-protein vaccine formulations can be rapidly modified to match alterations in influenza strains. The recent emergence of more virulent strains and the potential for a pandemic make it important that all new vaccine candidates be developed and tested. The experiments proposed here will define the capacity of PEA polymers to deliver polypeptide viral antigens by measuring both T cell stimulation and antibody production in response to diminished protein dosage. We propose to test polymer-coupled hemagglutinin and nucleoprotein antigens derived from H1N1 influenza for optimized dosage and schedule for influenza protection in mice. (Aim 1). We will test the ability of the vaccine candidates to protect animals from other influenza strains in mouse challenge studies (Aim 2). Finally, we will prepare the optimized formulations in several forms to assess their stability to storage in order to best prepare large quantities to use for human trials.(Aim 3) Successful achievement of these aims will provide impetus for development of commercially viable influenza vaccines that are rapidly prepared, stable in storage, and facile to transport to remote locales.

描述（由申请人提供）：临床免疫学面临的一个巨大挑战是开发合成疫苗，该疫苗在安全性、可靠性和成本方面优于传统方法。事实证明，将蛋白质和肽抗原适当递送至免疫系统是主要的技术障碍。近年来，由于生物可降解聚合物作为输送载体的发展，对这一问题的易处理解决方案的探索得到了巨大的推动。在这笔拨款中，我们引入了聚（酯酰胺）共聚物，作为当前合适的递送聚合物库的有价值的补充，并提出了支持性的初步概念验证实验，证明这些聚合物作为保护性疫苗的组成部分的用途对于流感。具体来说，这些聚合物蛋白疫苗制剂可以快速修改以匹配流感病毒株的变化。最近出现的毒性更强的毒株以及大流行的可能性使得开发和测试所有新的候选疫苗变得非常重要。这里提出的实验将通过测量响应蛋白质剂量减少的 T 细胞刺激和抗体产生来定义 PEA 聚合物递送多肽病毒抗原的能力。我们建议测试源自 H1N1 流感的聚合物偶联血凝素和核蛋白抗原，以优化小鼠流感保护的剂量和时间表。 （目标 1）。我们将在小鼠攻击研究中测试候选疫苗保护动物免受其他流感毒株侵害的能力（目标 2）。最后，我们将制备多种形式的优化制剂，以评估其储存稳定性，以便最好地制备大量用于人体试验的制剂。（目标3）这些目标的成功实现将为开发商业上可行的流感疫苗提供动力准备迅速，储存稳定，易于运输到偏远地区。