Cytokine and Costimulatory Factor-Encoding Plasmids as Adjuvants for DNA Vaccination

Abstract

The induction of a potent and long-lasting immunity is one of the most important elements to consider in developing an effective vaccine. DNA vaccines induce markedly stronger CD8⁺ cytotoxic T lymphocyte (CTL) activity than do traditional peptide vaccines through their particular mechanism of antigen presentation mediated by MHC class I molecules. Induction of CTL specific to pathogenic viruses is thought to provide a reliable means of protecting a host from infection and halting disease progression, as these cells can directly recognize and lyse infected cells. However, in most of the early studies showing induction of pathogen-specific CTL, antigen-encoding immunogenic DNA alone was used and DNA vectors encoding immunomodulating molecules were not considered. It now appears that various types of immunomodulatory molecules such as cytokines (IL-1 [1], IL-2 [2], IL-12 [3], IFN-γ [4], IL-7 [5–7], and GM-CSF [8,9]), chemokines (TCA-3 [10], RANTES [11], MIP-1 [11]), and costimulatory molecules (CD40L [12], B7-1 [13] and B7-2 [14]) could enhance or modify the specific immune responses elicited by DNA immunization (see Table 1).

Table 1 Summary of Effects of Cytokines after Conventional Vaccination and of Expression Plasmids following DNA Immunization