SYNTHETIC PEPTIDES TO DEVELOP SIMIAN RETROVIRAL VACCINE

不溶性SRV-2包膜肽88-103特异性结合恒河猴抗-

The insoluble SRV-2 envelope peptide 88-103 specifically binds rhesus anti- SRV-2 neutralizing antibodies. SRV-2 peptide 97-103 appears to the epitope that induces potential T cell activating properties of SRV-2 peptide 88-95, SRV-1 and SRV-2 envelope peptides shared by both virus. SRV-1 and SRV-2 peptide-KLH conjugates will be used to induce rhesus anti-envelope peptide neutralizing antibodies. These antibodies will be tested for their ability to block syncytium formation of virus in vitro, and when the rhesus monkeys make significant levels of SRV-1 or SRV-2 neutralizing antibody the animals will be challenged with the live SRV-1 or SRV-2 virus. SRV-1 or SRV-2 envelope peptides will be used to define epitopes involved in virus specific cytotoxic T lymphocyte (CTL) and/or antibody dependent cellular cytotoxicity (ADCC) responses. Characterization of epitopes associated with epitopes involved in CTL and ADCC responses will permit us to explore immunization protocols that might enhance virus-specific CTL and ADCC responses. Rhesus monkeys having enhanced CTL and/or ADCC responses may permit the development of virus-specific CTL cell lines and determine the role of CTL and/or ADCC responses in the protection against SRV-1 or SRV-2 virus infection. A NP40 extract of Raji cells will be used to isolate the receptor for virus binding. Affinity adsorbents prepared from SRV-1 peptide 150-157 or gp 70 will be used to isolate the putative receptor. Analysis of the receptor for virus binding will include 1) ability to block syncytial formation of virus growth in Raji cells, 2) direct binding of radiolabeled receptor with SRV-1 and/or SRV-2 virus, and 3) inhibition of radiolabeled peptide interaction with SRV-1 and/or SRV-2 virus. The isolated receptor will be used to prepare polyclonal and monoclonal anti-receptor antibodies. Our long term goal is to define SRV-1 and SRV-2 envelope peptides that can be used to induce enhanced neutralizing antibodies and/or CTL and ADCC virus-specific responses that can provide a vaccine to protect nonhuman primates from retroviral infections. The availability of isolated receptor and anti-receptor antibodies will be used to study virus-host cell interactions and define the range of cells that can be infected by virus.