DNA vaccines expressing antigens with a stress protein-capturing domain display enhanced immunogenicity

An expression system for DNA vaccines is described, in which a fusion protein with an N-terminal, viral J-domain that captures heat-shock proteins (Hsps) is translated in-frame with C-terminal antigen-encoding sequences (of various lengths and origins). The system supports enhanced expression of chimeric antigens (of >800 residues in length) with an extended half life (>8 h). When used as a DNA vaccine, it delivers antigen together with the intrinsic adjuvant activity provided by bound Hsps. We describe the design of vectors for DNA vaccination that support the expression of different immunogenic domains of different origins as large, Hsp-capturing chimeric fusion antigens. The immunogenicity of the antigens produced by this expression system (when it is built into DNA vaccines) has been characterized in detail, with particular emphasis on priming CD8+ T-cell responses. We also discuss areas of vaccine research to which the new technology may provide useful contributions.