Along with the elucidation of the role of cytotoxic T lymphocytes in the immune responses against a number of pathogens and
cancer, and with the increased understanding of the cellular processing mechanisms of
antigens for generation of these cells, has come an increased focus on
vaccines that can generate cellular immunity along with
antibodies. Promising approaches based on the delivery of genes, either as plasmid
DNA or by viral vectors, have been extensively evaluated pre-clinically and in early-phase clinical trials. Although the first generation of
DNA plasmid
vaccines were broadly effective in
animal disease models, early clinical immunogenicity pointed towards the need for increased potency. This manuscript reviews recent developments for gene-based
vaccines, specifically, new approaches for formulating and delivering plasmid
DNA and alphaviral replicon vectors, all of which have resulted in increased potency of gene-based
vaccines.