MATERNAL/NEONATAL IMMUNITY BY CHIMERIC IG AND NAKED DNA

生物技术的进步开创了疫苗研发的新纪元 这些发展是基于相应的多肽的利用 到保护性表位、重组蛋白、病毒或细菌载体 等。目前，开发安全疫苗存在许多困难。 这可以保护儿童免受传染病的侵袭。两条很有希望的途径 研究的是产妇免疫，它可能会提供保护 可为儿童提供保护的婴儿和新生儿免疫接种。 在过去的几年里，我们使用工程免疫球蛋白作为一种 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 两种疫苗母婴免疫效果评价 新疫苗使免疫球蛋白和裸露DNA抗原化。我们选择了流感病毒 系统，因为它为我们提供了一个方便的实验模型 有丰富的工作经验。我们的目标是了解基本的免疫力 抗原化Ig和Ig免疫母婴免疫机制的研究 裸露的DNA，可能导致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 CDR2环和CDR3环中的T细胞表位。 2.研究双抗原化Ig免疫新生儿的效果 关于抗HA体液和细胞反应及保护 预防流感病毒感染。根据所获得的信息，我们 建议研究佐剂最终增强反应的作用，以 确定保护性抗体的亚型和HA- 特定的B细胞克隆型。潜在的副作用也将是 已评估。 3.研究裸DNA免疫新生儿的效果。我们会 在本研究中使用含有流感病毒HA基因的质粒。我们的研究 被指定用来确定注射在新生儿体内的质粒半衰期， HA特异性抗体和CTL反应以及对病毒的保护。 潜在的副作用也将被研究。 4.评价抗原化免疫球蛋白和母体免疫效果。 关于保护后代免受流感病毒感染的裸露DNA。

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.