Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI037115-01
Application #
2073732
Study Section
Special Emphasis Panel (SRC (84))
Project Start
1994-09-30
Project End
1999-06-30
Budget Start
1994-09-30
Budget End
1995-06-30
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Radu, D L; Antohi, S; Bot, A et al. (2001) Effect of maternal antibodies on influenza virus-specific immune response elicited by inactivated virus and naked DNA. Scand J Immunol 53:475-82
Bot, A; Bot, S; Garcia-Sastre, A et al. (1998) Protective cellular immunity against influenza virus induced by plasmid inoculation of newborn mice. Dev Immunol 5:197-210
Antohi, S; Bot, A; Manfield, L et al. (1998) The reactivity pattern of hemagglutinin-specific clonotypes from mice immunized as neonates or adults with naked DNA. Int Immunol 10:663-8
Bot, A; Bot, S; Bona, C (1998) Enhanced protection against influenza virus of mice immunized as newborns with a mixture of plasmids expressing hemagglutinin and nucleoprotein. Vaccine 16:1675-82
Bot, A; Casares, S; Bot, S et al. (1998) Cellular mechanisms involved in protection against influenza virus infection in transgenic mice expressing a TCR receptor specific for class II hemagglutinin peptide in CD4+ and CD8+ T cells. J Immunol 160:4500-7
Bot, A; Antohi, S; Bot, S et al. (1997) Induction of humoral and cellular immunity against influenza virus by immunization of newborn mice with a plasmid bearing a hemagglutinin gene. Int Immunol 9:1641-50
Casares, S; Inaba, K; Brumeanu, T D et al. (1997) Antigen presentation by dendritic cells after immunization with DNA encoding a major histocompatibility complex class II-restricted viral epitope. J Exp Med 186:1481-6
Bot, A; Antohi, S; Bona, C (1997) Immune response of neonates elicited by somatic transgene vaccination with naked DNA. Front Biosci 2:d173-88
Bot, A; Bot, S; Antohi, S et al. (1996) Kinetics of generation and persistence on membrane class II molecules of a viral peptide expressed on foreign and self proteins. J Immunol 157:3436-42
Bot, A; Nangpal, A; Pricop, L et al. (1996) V lambda-light chain genes reconstitute immune responses to defined carbohydrate antigens or haptens by utilizing different VH genes. Mol Immunol 33:1359-68

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