The Immunology of DNA Vaccines

The surprising observation that direct inoculation of an expression plasmid encoding a foreign protein into the skin of mice resulted in the induction of antibody responses, demonstrated that injection of “naked” DNA could result in antigen expression in an immunogenic form (1 ). This observation and the subsequent demonstration that intramuscular injections of plasmid DNA encoding influenza nucleoprotein could protect mice against a challenge with live influenza virus have opened up new avenues for vaccine development (2 –3 ). Immunization with plasmid DNA has been shown to activate both humoral and cellular immune responses, including the generation of antigen-specific CD8⁺ cytotoxic T cells as well as CD4⁺ T helper cells (4 ). An increasing number of studies using experimental animal models have demonstrated that plasmid DNA immunization can promote effective immune responses against numerous viruses, including influenza, rabies, HIV, HBV, HCV, and HSV; several bacteria, including: Mycobacterium tuberculosis, Mycoplasma pulmonis , and Borrelia burgdorferi ; as well as parasites, such as malaria and leishmania (4 ). Phase I clinical vaccine trials are currently being performed for HIV, HBV, and influenza virus. With the molecular identification of tumor antigens (5 ), there has also been increasing interest in the development of DNA-based immunization for cancer. Preclinical studies demonstrate that DNA-based immunizations targeting model tumor antigens such as chicken ovalbumin (6 ), β-galactosidase (7 ), or CEA (8 ) induce protective immune responses leading to rejection of a subsequent, normally lethal challenge with antigen-expressing tumor cells.