Subsequent to our studies carried in 1977-79, demonstrating that the administration of syngeneic antiidiotypic antibodies (i.e. anti-460Id) caused the expansion of clones producing 460Id+ anti- TNP antibodies, numerous experimental data showed that anti-Id antibodies can be used as antigen surrogates or as idiotype vaccines. Several aspects underscore the attraction of using idiotypic vaccines in viral infections caused by viruses exhibiting genetic variations since it is envisioned that anti-idiotypic antibodies specific for a cross-reactive idiotype expressed on clones for various subtypes of virus could be broader than classical formalin inactivated vaccines.
The aims of our proposal are: 1. To select anted antibodies against monoclonal antibodies specific for hemagglutinin or neuraminidase of various subtypes of type A influenza virus or sequential virus variants and to investigate their ability to elicit an anti-hemagglutinin or neuraminidase response. The structure of variable region genes encoding the antibodies as will as of hemagglutinin gene of sequential variants will be studied to understand the molecular basis of mimicry of viral antigens by antibodies. 2. To produce monoclonal antibodies against envelope glycoprotein gp120, gp41 of HLTV-III and against a synthetic peptide corresponding to amino acid sequence 735 to 752 of the precursor envelope glycoprotein of HLTV-III virus. Antibodies specific for glycoproteins, synthetic peptides of HIV or CD4 of T cells will be used to produce anted antibodies which will be tested in experimental systems for their ability to elicit antiviral immunity. 3. To prepare hybrid molecules made up of murine V region of anted antibodies and constant region of human Ig in order to minimize the harmful immune reactions which could occur subsequent to the administration of foreign antibodies in humans.
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