The Signal Peptide Sequence Impacts the Immune Response Elicited by a DNA Epitope Vaccine

We examined the effect of two leader sequences, one from a transmembrane molecule (H2-Ld) and another from a secreted molecule (rat KC chemokine), on the immunogenicity of DNA epitope vaccines. The chemokine leader enhanced vaccine immunogenicity, thus underscoring the importance of the leader sequence in DNA epitope vaccine design. DNA vaccines have been shown to elicit strong humoral and cell-mediated immune responses in many animal models (2, 12, 13, 23). Studies suggest that the inoculated DNA is inter-nalized by the local antigen-presenting cells (APCs), which then express and present the plasmid-encoded antigen to cy-totoxic lymphocytes (CTLs) or T helper (TH) cells. Also, in vivo-transfected cells at the site of inoculation, such as kerati-nocytes and myocytes, can secrete the encoded antigen, which can be processed and presented by APCs (4, 6, 11, 23, 25). The immune responses elicited by DNA vaccines have had varied results in different animal models, underscoring the need for optimization (1, 22, 23). An advantage of DNA vac-cines is the ease with which one can introduce changes to qualitatively and quantitatively affect their immunogenicity (13, 23, 35). A number of approaches have been employed to enhance the efficacy of DNA vaccines, which include optimiz-ing antigen processing (24) and presentation (5, 9, 17, 27, 29–31, 33, 37), using epitope-carrier protein fusion molecule