Novel adjuvants for biodefense vaccines

用于生物防御疫苗的新型佐剂

• 批准号: 6859359
• 负责人: JOHN D CLEMENTS
• 金额: $ 27.08万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 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 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6859359
• 关键词: Bacillus anthracis; Yersinia pestis; bioterrorism /chemical warfare; botulinum toxins; cellular immunity; cooperative study; drug administration routes; humoral immunity; immunomodulators; laboratory mouse; mucosal immunity; pharmacokinetics; staphylococcal enterotoxin; vaccine development

DESCRIPTION (provided by applicant): An ideal vaccine against potential agents of biological warfare/bioterrorism should be safe, easy to deliver, provide long-lasting protection, require only one or a few doses, and provide protective immunity against different agents. Moreover, since mucosal and respiratory surfaces represent the first productive points of contact with the human host for many aerosolized biological agents, the role of mucosal immunity in protection needs to be examined. Nonparenteral delivery of vaccines (i.e., by the mucosal or transcutaneous route) has been shown to be effective at inducing both humoral and cellular antigen-specific immune responses in both the systemic and mucosal compartments of immunized animals and humans. Such "needle free" immunizations offer many potential advantages over parenteral immunization and are being evaluated by a number of groups for use in biodefense vaccines. Induction of immune responses by these nonparenteral routes is dependent upon the co-administration of appropriate adjuvants that can initiate and support the transition from innate to adaptive immunity. In this application we are proposing to investigate three novel adjuvants (LTR192G), CpG ODN, CTA1-DD) for their ability to induce high titer, long lived, protective antibody responses against relevant vaccine antigens from B. anthracis (rPA), Y. pestis (F1-V), botulinum toxin (Hc), and staphylococcal enterotoxin B (SEBv). The findings from these studies should be broadly applicable to other antigens from these and other biological agents. The primary objective of these studies is the optimization and preclinical testing of these novel adjuvants, each of which has previously shown promise in other infectious disease vaccines delivered mucosally or transcutaneously. It is expected that one or more of these adjuvants will be considered as candidates for future Phase I-II-III testing in clinical trial programs. Another objective of this application is to determine if nonparenteral boosting can induce a protective secondary immune response in animals that have been parenterally primed and if that response can be redirected to include a mucosal immune component. Challenge studies will allow us to correlate immune responses with protective efficacy and determine the contribution of mucosal immune responses to protection. Finally, we will determine the effectiveness of a combined vaccine consisting of relevant antigens from the four different pathogens with the specific objective of determining synergy or interference between the vaccine components and the role of adjuvants and route of delivery in overcoming interference.

描述（由申请人提供）：针对生物战/生物恐怖主义潜在制剂的理想疫苗应安全、易于接种、提供持久保护、仅需一剂或几剂，并提供针对不同制剂的保护性免疫。此外，由于粘膜和呼吸道表面代表了许多雾化生物制剂与人体宿主接触的第一生产点，因此需要检查粘膜免疫在保护中的作用。疫苗的非肠胃外递送（即，通过粘膜或经皮途径）已显示在免疫动物和人的全身和粘膜区室中有效诱导体液和细胞抗原特异性免疫应答。这种“无针”免疫接种提供了许多潜在的优势，超过肠胃外免疫接种，并正在评估由一些团体用于生物防御疫苗。通过这些非胃肠外途径诱导免疫应答取决于共同给予适当的佐剂，这些佐剂可以启动和支持从先天免疫向适应性免疫的转变。在本申请中，我们提出研究三种新型佐剂（LTR 192 G）、CpG ODN、CTA 1-DD）诱导针对来自B的相关疫苗抗原的高滴度、长寿命、保护性抗体应答的能力。anthracis（rPA）、Y.鼠疫杆菌（F1-V）、肉毒杆菌毒素（Hc）和葡萄球菌肠毒素B（SEBv）。这些研究的结果应广泛适用于这些和其他生物制剂的其他抗原。这些研究的主要目的是这些新型佐剂的优化和临床前测试，其中每一种佐剂先前都在粘膜或经皮递送的其他传染病疫苗中显示出前景。预计这些佐剂中的一种或多种将被视为临床试验计划中未来I-II-III期测试的候选物。 本申请的另一个目的是确定非胃肠外加强是否可以在已经胃肠外致敏的动物中诱导保护性二次免疫应答，以及该应答是否可以被重定向以包括粘膜免疫组分。攻毒研究将使我们能够将免疫应答与保护效力相关联，并确定粘膜免疫应答对保护的贡献。最后，我们将确定由来自四种不同病原体的相关抗原组成的联合疫苗的有效性，具体目标是确定疫苗组分之间的协同作用或干扰，以及佐剂和递送途径在克服干扰中的作用。