NEW STRATEGIES FOR IMMUNIZATION AGAINST INFLUENZA VIRUS

描述：（改编自申请人的摘要）长期 该提案的目的是开发一种新的有效疫苗 针对流感病毒，使用微球作为口服递送系统。 本II期研究的目的是优化免疫原性 粘膜接种流感病毒疫苗的潜力 生物可降解和生物相容性微球，并评估 这些疫苗在小鼠和松鼠中免疫预防潜力 猴流感感染模型。 最大和最佳数量 微球的摄入及其在胃肠道和胃肠道中的分布 呼吸道将通过监测 放射性标记的微球经口、鼻内或 对BALB/c小鼠全身性地。 微胶囊的最佳剂量 用于诱导分泌性免疫应答的流感病毒 将通过定量流感特异性 口服给药后小鼠血清和分泌物中的抗体 不同剂量的抗原（微囊化的相对于游离的）， 系统性挑战。 预先存在的分泌或 将在小鼠中测定循环抗体对免疫应答的影响 通过全身或粘膜途径引发并通过粘膜加强。 的 免疫接种诱导的免疫应答持续时间 微囊化抗原与游离抗原的比较将通过测量 一年的抗体滴度。 微球预充的能力 动物的继发性免疫反应与密切或不太相关 将在小鼠感染模型中测试流感病毒。 的 微囊化流感病毒粘膜免疫效果 还将通过测量活菌激发后的保护作用进行评价 松鼠猴体内的病毒 如果II期研究成功， 完成粘膜给药后的疗效评估 微囊化流感病毒的研究将在第三阶段继续进行， 人体试验

DESCRIPTION: (Adapted from the applicant's abstract) The long term objective of this proposal is to develop a new and effective vaccine against influenza virus, using microspheres as an oral delivery system. The purpose of this Phase II study is to optimize the immunogenic potential of mucosally administered influenza virus vaccine incorporated into biodegradable and biocompatible microspheres and to evaluate the immunoprophylactic potential of such vaccines in mouse and squirrel monkey influenza infection models. The maximum and optimal amount of microsphere uptake and their distribution in the gastrointestinal and respiratory tracts will be determined by monitoring the fate of radiolabeled microspheres administered orally, intranasally, or systemically to BALB/c mice. The optimal dose of microencapsulated influenza virus for inducing a secretory immune response without oral tolerance will be determined by quantitating the influenza-specific antibodies in sera and secretions of mice after oral administration of various doses of antigen (microencapsulated versus free) followed by systemic challenge. The influence of preexisting secretory or circulatory antibodies on the immune response will be determined in mice primed by systemic or mucosal routes and mucosally boosted. The duration of immune responses induced by immunization with microencapsulated versus free antigen will be characterized by measuring antibody titers of one year. The ability of microspheres to prime animals for secondary immune responses with closely or less related influenza viruses will be tested in a mouse infection model. The efficacy of mucosal immunization with microencapsulated influenza virus will also be evaluated by measuring protection after challenge with live virus in squirrel monkeys. If Phase II studies are successfully accomplished, the assessment of efficacy after mucosal administration of microencapsulated influenza virus will be continued in Phase III in a human trial.