Engineering DNA vaccination as an approach to HIV immune therapy

Deoxyribonucleic acid (DNA) vaccination, also known as genetic immunization, is a novel vaccine technology that has been tested in humans for many current infectious diseases, and has been found to be well-tolerated. The approach has been used to induce protective immunity against infectious pathogens, malignancies, as well as prevent the development of autoimmune disorders in animal models. Moreover, DNA vaccines have been tested for clinical use as both prophylactic and therapeutic agents. For these vaccines, plasmid DNA encoding a polypeptide/protein antigen is introduced into a host where it enters host cells and serves as an epigenetic template for the high efficiency translation of antigen. Although DNA immunogens have been shown to stimulate both the cellular and/or humoral arms of the immune system, improving the potency of these vaccines is clearly important. In this regard, several approaches to improve efficacy are currently being tested and will be discussed in this review. One such approach is to improve the DNA plasmid by introducing codon optimization in the DNA plasmid that improves expression and immunogenicity in animals. A second approach aims to manipulate the host immune response by including immunologic molecular adjuvants as part of the vaccine including T cell costimulatory molecules, cytokines, and chemokines. Using immunologic adjuvants, researchers have tailored the immune response to the DNA vaccine toward a particular Th subtype, allowing for the preferential induction of predominantly cell-mediated or humoral response. In particular, interleukin-15 (IL-15) expands CD8 immune responses in the absence of T cell help, while chemokines attract dendritic cells as well as other professional antigen presenting cells, directly activating T and/or B cells in the periphery. Furthermore, priming with such adjuvanted DNAs and boosting with T cell costimulatory molecules further enhances antigen-specific immune response to the DNA antigen. Combining these approaches may be particularly useful against human immunodeficiency virus (HIV) infection, in which both cell-mediated and humoral immune responses are required to fight infection. Ultimately, clinical evidence of these approaches may influence not just how we approach HIV treatment, but also treatments for other infectious diseases, autoimmunity, and cancer.