MATERNAL/NEONATAL IMMUNITY BY CHIMERIC IG AND NAKED DNA

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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.