Multiplexed vaccine titer test

描述(申请人提供)：到1990年，免疫努力几乎消除了儿童疾病，如脊髓灰质炎、麻疹和腮腺炎，但新疫苗的迅速推出可能矛盾地促进了复发，因为复杂的注射程序减少了父母和医生的依从性。疫苗制造商已经推出了多价疫苗，提供针对多种制剂的单次注射保护。除了麻疹、腮腺炎和风疹疫苗(MMR)外，白喉类毒素、破伤风类毒素和无细胞百日咳(DTaP)、灭活脊髓灰质炎病毒(IPV)、b型流感嗜血杆菌(Hib)和/或乙肝(Heb)的五价组合已获批准，其他药物仍在开发中。疫苗范围的扩大和多价疫苗产生了对具有成本效益的、高度多样化的血清学检测的需求，以确定对每种成分的抗体反应。需要新的测试，既作为评估对每个患者的保护的筛查分析，也作为疫苗开发的工具，以检测新组合中每个目标的有效性。 传统的多孔ELISA法免疫分析费时费力，与多分析物检测的匹配性差。流式细胞仪珠阵免疫分析可以用一种小型化、多重化、快速、灵敏和特异的方法来取代这种ELISA法。尽管用于血清学监测疫苗接种和感染的珠粒阵列具有商业潜力，但与细胞因子面板等多路夹心免疫分析相比，这一市场仍未开发。一个关键的限制是需要用不同的抗原包覆珠子，包括蛋白质、多糖和整个病毒颗粒，这需要广泛的固定化化学物质，必须独立优化。就全面的疫苗接种和感染检测将需要&gt；50-plex测试而言，制备坚固和可重复使用的珠板的挑战是一个重大障碍。 这份意见书建议克服目前分析的局限性，并通过开发允许利用新的化学方法快速多路传输不同抗原的方案以及无论抗原是碳水化合物、蛋白质还是病毒而将珠子包覆的分析设计来扩大珠阵列免疫分析的潜力。这将导致用于筛选对所有已获批准的疫苗的反应和接触最常见的传染病有机体的试剂盒。重要的是，这些试剂盒是完全动态的，可以进行修改以反映新的疫苗、新的传染病血清型和/或新发现的疾病生物体。这个平台有可能被设计成在第三世界使用。 公共卫生相关性：多价疫苗滴度测试快速确定对多价疫苗应答水平的标准化方法尚未开发出来。标准化测试的提供将有助于更有效地开发新的多价疫苗，并确定疫苗在接种疫苗的儿童和成人中的效力。在这份意见书中，我们建议开发一种平台技术，使疫苗效力的快速、经济有效和敏感的标准化测试成为可能。

DESCRIPTION (provided by applicant): Immunization efforts had all but eliminated childhood diseases such as polio, measles, and mumps by 1990, but the rapid introduction of new vaccines may paradoxically be promoting reemergence as complex injection schedules decrease compliance by parents and physicians. Vaccine manufacturers have responded with multivalent vaccines that provide single-injection protection against multiple agents. In addition to the measles, mumps and rubella vaccine (MMR), pentavalent combinations of diptheria toxoid, tetanus toxoid, and acellular pertussis (DTaP), inactivated polio virus (IPV), Haemophilus influenzae Type b (Hib), and/or hepatitis B (HepB), have been approved and others remain in development. The increasing range and multivalency of vaccines has created a need for cost-effective, highly multiplexed serological testing to determine antibody response to each component. New tests are needed both as screening assays to evaluate protection of each patient and as a tool for vaccine development to detect efficacy for each target in novel combinations. The traditional multiwell ELISA format immunoassay is laborious and poorly matched to multianalyte testing. Flow cytometric bead array immunoassays can replace such ELISA format assays with a miniaturized, multiplexed, rapid, sensitive and specific alternative. Despite the commercial potential of bead arrays for serology to monitor vaccination and infection, this market remains undeveloped compared to multiplexed sandwich immunoassays such as cytokine panels. A key limitation is the need to coat beads with diverse antigens, including proteins, polysaccharides, and whole virus particles, which requires a wide range of immobilization chemistries that must be independently optimized. Insofar as a comprehensive vaccination and infection assay will require >50-plex testing, the challenge of preparing robust and reproducible bead panels is a significant barrier. This submission proposes to overcome the limitations of current assays and expand the potential of the bead array immunoassay by the development of protocols that allow rapid multiplexing of diverse antigens employing novel chemistries and assay design to coat beads independent of whether the antigen is a carbohydrate, protein or virus. This will lead to kits for screening for responses to the full range of approved vaccines and for exposure to the most common infectious organisms. Importantly, these kits are completely dynamic and can be modified to reflect new vaccines, new infectious disease serotypes and/or newly discovered disease organisms. This platform has the potential to be engineered for use in the third world. PUBLIC HEALTH RELEVANCE: Multivalent Vaccine Titer Test A standardized method to rapidly determine the level of response to multivalent vaccines has not been developed. Availability of a standardized test would allow more efficient development of new multivalent vaccines as well as determining effectiveness of vaccines in vaccinated children and adults. In this submission we propose the development of a platform technology that will allow rapid, cost effective and sensitive standardized testing for vaccine efficacy.