Priming polyvalent immunity by DNA vaccines expressing chimeric antigens with a stress protein-capturing, viral J-domain

SPECIFIC AIMSFusion constructs containing an amino-terminal hsp73 binding, DnaJ-like domain of SV40 T-Ag and carboxyl-terminal sequences encoding fragments of unrelated viral proteins showed strikingly enhanced and stable expression. We intend to develop new DNA vaccine constructs using this novel expression system for the efficient and selective expression of different antigenic epitopes combined with the innate adjuvanticity of hsp molecules (known to enhance and modulate the immunogenicity of antigens).PRINCIPIAL FINDINGS1. Hsp73 binds mutant SV40 T-Ag proteins with an intact NH2 terminusMolecular chaperones such as heat shock proteins (hsp) assist in protein folding, degradation, and traffic. Some members of the hsp70 family, the abundantly and constitutively expressed hsp73 (hsc70) in the cytosol of mammalian cells, can stabilize mutant proteins but also facilitate their elimination in a novel lysosomal degradation pathway for intracellular proteins. Expression as an hsp73-associated complex seems an...