DNA vaccines: are they still just a powerful tool for the future?

Abstract

Vaccination is historically one of the most successful strategies for the prevention of infectious diseases. For safety reasons, modern vaccinology tends toward the usage of inactivated or attenuated microorganisms and uses predominantly subunit vaccines. The antigens need to be clearly defined, pure, stable, appropriately composed, and properly presented to the immune system of the host. Differing ratios of various proportions between specific CD4+ and CD8+ T cell responses are essential for conferring the required protection in the case of individual vaccines. To stimulate both CD4+ and CD8+ T cells, the antigens must be processed and presented to both antigen-presentation pathways, MHC I and MHC II. Protein antigens delivered by vaccination are processed as extracellular antigens. However, extracellularly delivered antigen can be directed towards intracellular presentation pathways in conjugation with molecules involved in antigen cross-presentation, e.g. heat shock proteins, or by genomic-DNA vaccination. In this overview, current knowledge of the host immune response to DNA vaccines is summarized in the introduction. The subsequent sections discuss techniques for enhancing DNA vaccine efficacy, such as DNA delivery to specific tissues, delivery of DNA to the cell cytoplasm or nucleus, and enhancement of the immune response using molecular adjuvants. Finally, the prospects of DNA vaccination and ongoing clinical trials with various DNA vaccines are discussed.

Induction of Protective Immune Responses by a Multiantigenic DNA Vaccine Encoding GRA7 and ROP1 of Toxoplasma gondii

“…DNA vaccination can protect animals and human beings against pathogenic microorganisms, particularly intracellular parasites (1). In the present study, BALB/c mice immunized intramuscularly with pGRA7, pROP1, or pGRA7-ROP1 produced specific antibodies against T. gondii GRA7 and/or ROP1, and protective immunity was induced.…”

“…DNA vaccines have become a major focus, because they promote the specific expression of an encoded vaccine antigen by host cells and have the ability to deliver multivalent vaccines to a host in a single dose. Additionally, DNA vaccines can also elicit potent, long-lasting humoral and cell-mediated immunity (1). The family of vaccine candidate antigens includes T. gondii membrane-associated surface antigens SAG1 (10,18) and SAG2 (4); excreted-secreted dense-granule proteins GRA1 (8,9), GRA2 (11), GRA4, GRA6 (8), and GRA7 (3,8,9,16); rhoptry proteins ROP1 (3,10) and ROP2 (9,18); and micronemal proteins MIC1, MIC2, MIC3 (14), and MIC6 (13).…”

A New Broad Range Plasmid for DNA Delivery in Eukaryotic Cells Using Lactic Acid Bacteria: In Vitro and In Vivo Assays

“…The strategy of bactoinfection (live bacterial vectors for transfection of mammalian cells) opened the field to use L. lactis as a DNA delivery vehicle 8, 9. DNA delivery by bacteria into eukaryotic cells leads to host expression of post-translational modified antigens and consequently the presentation of conformational-restricted epitopes to the immune system 10 . Several studies have used native 11 or recombinant L. lactis expressing different invasin, describing their potential uses as DNA delivery vectors either in vivo or in vitro assays 12, 13, 14…”

Induction of immune responses in sheep by vaccination with liposome-entrapped DNA complexes encoding Toxoplasma gondii MIC3 gene

“…We have focused on the development of a DNA-based vaccine because such vaccines have been shown to elicit potent, long-lasting humoral and cell-mediated immunity, as well as providing protection against viral, bacterial, and parasitic infections (Beláková et al 2007). The most common method used to deliver DNA vaccines is intramuscular injection which is known to induce a Th1-type response.…”