Abstract

The overall objective is to develop a new vaccine approach based on the preparation of anti-Id antibodies able to stimulate the humoral and cellular anti-influenza virus immunity. The major thrust of this proposal is based on our previous studies demonstrating shared idiotopes among antibodies specific for hemagglutinin and neuraminidase of various virus subtypes, among antibodies specific for laboratory induced variants and an interspecies cross-reactive idiotype shared by human and murine anti- PRB antibodies. The proposed study bears upon: 1) Preparation of anti-id antibodies against antibodies specific for laboratory induced variants and studies of their effects on humoral responses and viral replication. 2) Immortalization of human B cell clones producing antibodies specific for the Idx expressed on murine and human anti-PRB antibodies and to determine in vitro which of these antibodies stimulate influenza virus specific clones. 3) Studies of the effects of antibodies on cellular responses and viral replication. The effects of three types of antibodies will be studied a) anti-TCR antibodies, b) a hybrid bifunctional antibody (specific for TCR of CTL and HA of influenza virus) which can efficiently focus CTL on infected target cells. c) a genetically engineered antibody containing an inserted viral epitope. These studies are aimed to determine the enhancing effects of anti-id antibodies on immune reaction against influenza virus, a system in which vaccines produced by classical approaches has not succeed in overcoming epidemics resulting from a high potential for natural antigenic variation of the virus.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018316-11
Application #
3127844
Study Section
Experimental Virology Study Section (EVR)
Project Start
1981-08-01
Project End
1994-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
11
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

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

  Publications

Zaghouani, H; Kuzo, Y; Kuzo, H et al. (1993) Engineered immunoglobulin molecules as vehicles for T cell epitopes. Int Rev Immunol 10:265-78
Zaghouani, H; Steinman, R; Nonacs, R et al. (1993) Presentation of a viral T cell epitope expressed in the CDR3 region of a self immunoglobulin molecule. Science 259:224-7
Kuzu, H; Kuzu, Y; Zaghouani, H et al. (1993) In vivo priming effect during various stages of ontogeny of an influenza A virus nucleoprotein peptide. Eur J Immunol 23:1397-400
Kuzu, Y; Kuzu, H; Zaghouani, H et al. (1993) Priming of cytotoxic T lymphocytes at various stages of ontogeny with transfectoma cells expressing a chimeric Ig heavy chain gene bearing an influenza virus nucleoprotein peptide. Int Immunol 5:1301-7
Brumeanu, T D; Kohanski, R; Bona, C A et al. (1993) A sensitive method to detect defined peptide among those eluted from murine MHC class II molecules. J Immunol Methods 160:65-71
Zaghouani, H; Kuzu, Y; Kuzu, H et al. (1993) Contrasting efficacy of presentation by major histocompatibility complex class I and class II products when peptides are administered within a common protein carrier, self immunoglobulin. Eur J Immunol 23:2746-50
Usuba, O; Schulman, J L; Deatly, A M et al. (1990) New method for titration of virus infectivity by immunostaining. Viral Immunol 3:237-41
Ito, M; Usuba, O; Unkeless, J C et al. (1989) Sideways killing: the cytolysis of Fc receptor-bearing cells through bridging to cytolytic T lymphocytes by antibodies specific for the T-cell receptor-T3 complex. Scand J Immunol 29:659-69
Meek, K; Johansson, B; Schulman, J et al. (1989) Nucleotide changes in sequential variants of influenza virus hemagglutinin genes and molecular structures of corresponding monoclonal antibodies specific for each variant. Proc Natl Acad Sci U S A 86:4664-8
Ertl, H C; Bona, C A (1988) Criteria to define anti-idiotypic antibodies carrying the internal image of an antigen. Vaccine 6:80-4

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