Vinciane Dufour Service de Biologie Moleculaire, Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Ploufragan, Brittany, France
Introduction
In 1990, Wolff and his colleagues were the first to report the successful expression of naked plasmid DNA in mouse muscle tissue [108]. A few years later it was reported that the injection of DNA encoding an antigenic protein of influenza virus conferred protective immunity in mice [97]. Many papers have described and reviewed the protective immunity induced by DNA against a large variety of viruses [20], bacteria [90] and protozoa [47] in murine models. DNA immunisation has also been investigated for the treatment of cancer [6] and autoimmune diseases [72]. Trials are now being developed for human DNA vaccines against several diseases such as AIDS and malaria [96, 104]. The administration of a simple plasmid can induce a broad spectrum of immune responses [54]. They include the activation of CD8+ T lymphocytes, implicated in host defense against intracellular pathogens via cytotoxic T lymphocytes (CTL), and CD4+ T lymphocytes, which secrete cytokines and play a role in B cell production of specific antibodies (Figure 1). Despite its potential impact on protective immunity, however, DNA vaccination is not always successful. Protective immunity depends mostly on the immunogenicity of a pathogen’s antigen, but other factors such as the frequency and route of administration, the amount of DNA, the localisation of the plasmid codedantigen (secreted, membrane-bound or cytoplasmic), and the age, health and species of the animals vaccinated, have an affect.
Principle and advantages
Characteristics of the expression vectors The first vectors used for DNA vaccination were bacterial plasmids, developed originally for the in vitro expression of foreign protein in mammalian cells [28]. A plasmid contains a prokaryotic replication origin that allows high-yield