Synthetic Peptide Vaccines for the Control of Arenavirus Infections

摘要

Arenaviruses are endemic on both the African and South American continents andrepresent significant public health hazards. Prophylactic immunization, precise diagnostic methods, and effective treatment protocols are not currently available. We are using genetic cloning methods to develop an effective vaccine against arenaviruses. Developmental studies have been carried out and techniques established with the prototype arenavirus, lymphocytic choriomeningitis virus (LCMV), and these methods can now be applied for rapid development and evaluation of vaccines against the pathogenic arenaviruses Lassa, Junin, and Machupo. Using techniques of peptide and immunochemistry we have identified and mapped the gene products of the L and S-RNA segments of LCMV and mapped the important immunogenic regions of the viral glycoproteins. The LCMV genomic RNAs have been cloned and primary sequences of the RNAs and their gene products are being completed. synthetic peptides corresponding to immunogenic regions of the viral structural proteins are being synthesized and will be evaluated for the ability to induce immune responses in experimental animals. Experimental approaches to immunization based upon synthetic peptides and polypeptides, vaccinia virus vectors containing LCMV genes, and anti-idiotypic antibodies will be explored and immunotherapy for acute arenavirus infections will be investigated using cloned cytotoxic T-lymphocytes and neutralizing monoclonal antibodies in attempts to modify the course of acute disease.