Current State of the Art in DNA Vaccine Delivery and Molecular Adjuvants: Bcl-xL Anti-Apoptotic Protein as a Molecular Adjuvant

Abstract

DNA vaccines (nucleic acid vaccines) have been gaining importance as promising therapeutics against infectious diseases, cancer, autoimmune disorders and allergy for the past two decades. However, the immune responses elicited by the DNA vaccines are not at the desired level to stimulate a protective immune response. Thus, studies are focused on the enhancement of DNA vaccine-induced immune response by different approaches. The most common approach is to use biomaterial-based adjuvants for enhanced antigen delivery and uptake by antigenpresenting cells. Some of these adjuvants are alum, saponins, microspheres, nanoparticles, liposomes, polymers, etc. used in vaccine formulations. In addition, molecular adjuvants like cytokines, chemokines and heat shock proteins have been shown to be promising in designing DNA vaccines. In this chapter, molecular adjuvants to improve DNA vaccination-induced immune responses will be summarized with a special focus on Bcl-xL anti-apoptotic protein.

Strategies in DNA vaccine for melanoma cancer

“…In viral delivery systems, viruses including adenoviruses, adenoassociated viruses, lentiviruses, and retroviruses, as the gene carriers are modified to deliver therapeutic genes to target cells without creating viral disease, showing promising potential for efficient transfection of target DNA to the cells. In this delivery system, genetic material, after transfection may remain as an episomal element or be integrated into the host genome, the latter leads to stable protein expression for a prolonged time but also increases the potential of oncogenic mutagenesis (Gulce-Iz & Saglam-Metiner, 2019). Moreover, despite their significance, as an efficient delivery tool with high transfection rates in the development of DNA vaccines, viral delivery systems suffer some disadvantages and drawbacks including the possibility of reversion to wildtype virus, the induction of innate immune responses, preexisting immunity against the virus.…”

“…Physical delivery systems are referred to approaches during which a physical force is used to make cell membrane permeable and facilitate direct intracellular gene transfection, mostly in the form of pDNA alone. Among different physical gene transfection delivery systems, microinjection, gene gun (the ballistic DNA delivery) and electroporation are the most promising methods for in vivo gene transfection (Gulce-Iz & Saglam-Metiner, 2019;Mellott et al, 2013). Although they lead to high efficient transfection of target DNA into cells, physical delivery systems have some disadvantages including low activity due to tissue damage caused by applied physical forces; limiting the application of such methods (Xiang et al, 2010).…”

Plasmid Replicons for the Production of Pharmaceutical-Grade pDNA, Proteins and Antigens by Lactococcus lactis Cell Factories

“…Subsequently, L. lactis cells are grown at a large scale for pDNA production and purification. The purified DNA vaccine is then introduced into host eukaryotic cells (e.g., dendritic or epithelial cells) [ 41 , 42 , 45 ], by an appropriate delivery method (e.g., viral gene delivery systems, microinjection, gene gun, biojector, electroporation, ultrasound) [ 46 ]. After escaping the phagolysosome, the pDNA is transcribed, then the translated antigen can be presented (by using appropriate targeting signals) at the cytoplasm, at the cell surface or secreted.…”

Nucleic acid vaccines: A taboo broken and prospect for a hepatitis B virus cure

“…DNA vaccine platforms have many advantages: they are fast to develop, easy to replicate, and very stable at room temperature, resulting in low manufacturing and storage costs[ 19 ]. Theoretically, they are safer than conventional live attenuated vaccines because they do not elicit potential anti-vector immune responses and by continuously expressing antigens elicit a long-lasting response without being infectious[ 20 ]. Moreover, the intracellular synthesis of the encoded antigens enables the endogenous post-translational modifications that generate proteins in their native conformation[ 18 ].…”