MATERNAL/NEONATAL IMMUNITY BY CHIMERIC IG AND NAKED DNA

生物技术的进步开创了疫苗开发的新时代 这些发展是基于利用相应的肽 保护性表位、重组蛋白、病毒或细菌载体 等目前，研制安全疫苗面临诸多困难 可以保护儿童免受传染源的侵害。两个有希望的途径 研究的重点是母亲免疫接种， 婴儿和新生儿免疫接种，可为儿童提供保护。 在过去的几年里，我们使用工程免疫球蛋白作为 用于病毒B和T细胞表位的递送系统。 我们提案的总体目标是利用流感病毒系统， 评价两种疫苗的母婴免疫效果 新疫苗抗原化的IG和裸DNA。我们选择流感病毒 因为它提供了一个方便的实验模型， 经验丰富。我们的目标是了解基本的免疫 用抗原化的IG进行母体和母体免疫的机制， 裸DNA，这可能导致针对流感病毒的保护性反应。 因此，具体目标是： 1.构建携带流感病毒的双抗原化lg分子 血凝素B和T细胞表位。将表达B细胞表位 在CDR 2环和CDR 3环中的T细胞表位。 2.目的探讨双抗原化IG在新生儿免疫中的作用 关于抗HA体液免疫和细胞应答和保护 预防流感病毒感染。根据获得的信息，我们 建议研究佐剂最终增强反应， 确定保护性抗体的同种型和HA的模式- 特异性B细胞克隆型。潜在的副作用也将是 评估。 3.目的探讨裸DNA免疫新生儿的效果。 我们将 本研究使用含流感病毒HA基因的质粒。我们的研究 被指定用于确定注射到新生儿中的质粒的半衰期， HA特异性抗体和CTL应答以及抗病毒的保护作用。 还将研究潜在的副作用。 4.目的评价抗原化IG母源免疫的效果， 裸DNA对保护后代免受流感病毒感染的作用。

Advances in biotechnology have ushered in a new era of vaccine development These developments are based on the utilization of peptides corresponding to protective epitopes, recombinant proteins, viral or bacteria vectors etc. At present, there are many difficulties in developing safe vaccines that can protect children against infectious agents. Two promising avenues of research are maternal immunization which may confer protection to infants and neonatal immunization which may confer protection to children. During the past years, we have used engineered immunoglobulins as a delivery system for viral B and T cell epitopes. The overall goal of our proposal is to use the influenza virus system to evaluate the effects of maternal and neonatal immunization of two types of new vaccine antigenized Ig and naked DNA. We choose the influenza virus system because it provides a convenient experimental model with which we have extensive experience. Our aims are to understand the basic immune mechanisms of maternal and neonataI immunization with antigenized Ig and naked DNA which may lead to protective response against influenza virus. Thus, the specific aims are: 1. To construct a doubly antigenized lg molecule bearing influenza virus hemagglutinin B and T cell epitopes. The B cell epitope will be expressed in CDR2 loop and T cell epitope in CDR3 loop. 2. To study the effect of neonatal immunization with doubly antigenized Ig with respect to anti-HA humoraI and cellular responses and protection against influenza virus infection. Based on information obtained, we propose to study the eventual enhancement of responses by adjuvants, to determine the isotypes of protective antibodies and the pattern of HA- specific B cell clonotypes. The potential side effects will also be evaluated. 3. To study the effect of neonatal immunization with naked DNA. We will use in this study a plasmid containing influenza virus HA gene. Our studies are designated to determine the half life of plasmids injected in neonates, HA specific antibody and CTL response and the protection against virus. The potential side effects will also be studied. 4. To evaluate the effects of maternal immunization with antigenized Ig and naked DNA on the protection of offspring against influenza virus infection.