NEW STRATEGIES FOR IMMUNIZATION AGAINST INFLUENZA VIRUS

描述：（改编自研究者摘要） 拟议的I期研究是探索一种新的方法， 通过使用微囊化抗原经口服或口服施用的疫苗接种， 鼻内途径以诱导保护性粘膜免疫应答。 将用纯化的A型H3N2流感病毒（Udorn）免疫小鼠 游离于溶液中或包封在可生物降解的微球中，通过口服， 鼻内或全身途径。 诱导的， 将在血清和分泌物中测定抗原特异性免疫球蛋白 从免疫的小鼠中收集。 所获得的数据将与 与抗原递送的形式（游离于溶液中或 在微球中）和给药途径（全身、口服或 鼻内）。 预计这些研究将提供以下信息： 诱导具有保护作用的抗体的最有效途径 预防流感病毒感染。 使用的潜在优势 作为抗原递送载体的生物相容性和可生物降解的微球 包括：保护和控制释放相对高量 抗原，佐剂作用，和选择性刺激分泌或 根据微球的大小来确定全身免疫应答。 后 建立微囊化流感病毒的免疫原性 在第一阶段研究中，这些研究将在第二阶段继续进行， 另一种动物模型，松鼠猴。 这种模式更适合于 由于猴和猴之间的相似性， 和人体免疫系统，并且由于一种 流感病毒（Udorn）适应于在猴子中传染。

DESCRIPTION: (Adapted from the Investigator's Abstract) The purpose of the proposed Phase I study is to explore a novel approach for influenza virus vaccination by using microencapsulated antigen administered by the oral or intranasal route in order to induce a protective mucosal immune response. Mice will be immunized with purified influenza virus type A H3N2 (Udorn) free in solution or encapsulated in biodegradable microspheres, by oral, intranasal, or systematic routes. The levels and isotype of the induced, antigen-specific immunoglobulins will be determined in sera and secretion collected from the immunized mice. The data obtained will be correlated with the form by which the antigen was delivered (free in the solution or in microspheres) and with the route of administration (systemic, oral, or intranasal). These studies are expected to provide information concerning the most effective route for induction of antibodies with a protective role against influenza virus infections. Potential advantages for using biocompatible and biodegradable microspheres as an antigen delivery vehicle include: protection and controlled release of relatively high amounts of antigen, an adjuvant effect, and selective stimulation of secretory or systemic immune response according to the size of microspheres. After establishing the immunogenicity of microencapsulated influenza virus in mice in Phase I research, the studies will be continued in Phase II in another animal model, squirrel monkeys. This model is more suitable for assessment of vaccine efficacy because of the similarities between monkey and human immune systems and because of the availability of a strain of influenza virus (Udorn) adapted to be infective in monkeys.