DNA vaccines for targeting bacterial infections

Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Expert Review of Vaccines (Impact Factor: 4.21). 07/2010; 9(7):747-63. DOI: 10.1586/erv.10.57
Source: PubMed


DNA vaccination has been of great interest since its discovery in the 1990s due to its ability to elicit both humoral and cellular immune responses. DNA vaccines consist of a DNA plasmid containing a transgene that encodes the sequence of a target protein from a pathogen under the control of a eukaryotic promoter. This revolutionary technology has proven to be effective in animal models and four DNA vaccine products have recently been approved for veterinary use. Although few DNA vaccines against bacterial infections have been tested, the results are encouraging. Because of their versatility, safety and simplicity a wider range of organisms can be targeted by these vaccines, which shows their potential advantages to public health. This article describes the mechanism of action of DNA vaccines and their potential use for targeting bacterial infections. In addition, it provides an updated summary of the methods used to enhance immunogenicity from codon optimization and adjuvants to delivery techniques including electroporation and use of nanoparticles.

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    • "DNA vaccination has been of great interest since its discovery Q5 in the 1990s as it can stimulate both cell-mediated and humoral immune responses [1]. It is known that intramuscular injection of plasmid DNA can induce antibodies, helper and cytotoxic T cell responses, against different viral and bacterial infections in animal models [2]. "
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    ABSTRACT: Lactococcus lactis (L. lactis), a generally regarded as safe (GRAS) bacterium has recently been investigated as a mucosal delivery vehicle for DNA vaccines. Because of its GRAS status, L. lactis represents an attractive alternative to attenuated pathogens. Previous studies showed that eukaryotic expression plasmids could be delivered into intestinal epithelial cells (IECs) by L. lactis, or recombinant invasive strains of L. lactis, leading to heterologous protein expression. Although expression of antigens in IECs might lead to vaccine responses, it would be of interest to know whether uptake of L. lactis DNA vaccines by dendritic cells (DCs) could lead to antigen expression as they are unique in their ability to induce antigen-specific T cell responses. To test this, we incubated mouse bone marrow-derived DCs (BMDCs) with invasive L. lactis strains expressing either Staphylococcus aureus Fibronectin Binding Protein A (LL-FnBPA+), or Listeria monocytogenes mutated Internalin A (LL-mInlA+), both strains carrying a plasmid DNA vaccine (pValac) encoding for the cow milk allergen β-lactoglobulin (BLG). We demonstrated that they can transfect BMDCs, inducing the secretion of the pro-inflammatory cytokine IL-12. We also measured the capacity of strains to invade a polarized monolayer of IECs, mimicking the situation encountered in the gastrointestinal tract. Gentamycin survival assay in these cells showed that LL-mInlA+ is 100 times more invasive than L. lactis. The cross-talk between differentiated IECs, BMDCs and bacteria was also evaluated using an in vitro transwell co-culture model. Co-incubation of strains in this model showed that DCs incubated with LL-mInlA+ containing pValac:BLG could express significant levels of BLG. These results suggest that DCs could sample bacteria containing the DNA vaccine across the epithelial barrier and express the antigen. Copyright © 2015. Published by Elsevier Ltd.
    Vaccine 08/2015; 33(38). DOI:10.1016/j.vaccine.2015.07.077 · 3.62 Impact Factor
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    • "According to Tian et al. (2008), a DNA vaccine expressing both seven epitopes which derived from the subunits S1 and S2 and the nucleoprotein N, stimulates strong humoral and cellular immune responses and provides protection that exceeds 80%. Polyvalent vaccines utilization is encouraged with DNA vaccines; several sequences encoding various Ag and cytokines can be introduced together into the same bacterial promoter (Ingolotti et al., 2010). In fact, the vaccinia virus is characterized by the large size of its genome which allows the integration of several viral genes. "
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    ABSTRACT: Infectious Bronchitis (IB) of chicken is a viral disease caused by a Coronavirus (IBV). It is worldwide distributed and characterized by its heavy economic impact on the poultry industry. The objective of this study is to elucidate the molecular aspect of the IBV, to describe the humoral and cellular immune responses, especially those played by cytotoxic T lymphocytes in the control of this infection in addition to the role played by each of the viral proteins S and N in the induction of those immune reactions. Biotechnological advances (especially gene therapy) in the IB control have been assessed by several researchers; however they are still facing some constraints. Development of new vaccines against IBV involves detailed knowledge of its antigenic structure and of the specific Cytotoxic T Lymphocytes (CTL) epitopes.
    Asian Journal of Poultry Science 03/2015; 9(2). DOI:10.3923/ajpsaj.2015.57.69
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    • "Two decades ago deoxyribonucleic acid-based immunization (DNA vaccination) initiated a new era of vaccine research and since then it has become an extremely powerful tool to develop new antiviral vaccines [1]. Four DNA vaccine products have already been licensed for animal health applications [2] [3]. Among them, the vaccine against the fish novirhabdovirus infectious hematopoietic necrosis (IHNV) is one of the most successful DNA vaccines developed so far. "
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    ABSTRACT: We have recently identified the two major determinants of the glycoprotein G of the viral hemorrhagic septicaemia rhabdovirus (gpGVHSV), peptides p31 and p33 implicated in triggering the host type I IFN antiviral response associated to these rhabdoviral antigens. With the aim to investigate the properties of these viral glycoprotein regions as DNA molecular adjuvants, their corresponding cDNA sequences were cloned into a plasmid (pMCV1.4) flanked by the signal peptide and transmembrane sequences of gpGVHSV. In addition, a plasmid construct encoding both sequences p31 and p33 (pMCV1.4-p31+p33) was also designed. In vitro transitory cell transfection assays showed that these VHSV gpG regions were able to induce the expression of type I IFN stimulated genes as well as to confer resistance to the infection with a different fish rhabdovirus, the spring viremia of carp virus (SVCV). In vivo, zebrafish intramuscular injection of only 1μg of the construct pMCV1.4-p31+p33 conferred fish protection against SVCV lethal challenge up to 45 days post-immunization. Moreover, pMCV1.4-p31+p33 construct was assayed for molecular adjuvantcity's for a DNA vaccine against SVCV based in the surface antigen of this virus (pAE6-GSVCV). The results showed that the co-injection of the SVCV DNA vaccine and the molecular adjuvant allowed (i) a ten-fold reduction in the dose of pAE6-Gsvcv without compromising its efficacy (ii) an increase in the duration of protection, and (iii) an increase in the survival rate. To our knowledge, this is the first report in which specific IFN-inducing regions from a viral gpG are used to design more-efficient and cost-effective viral vaccines, as well as to improve our knowledge on how to stimulate the innate immune system.
    Vaccine 09/2014; 32(45). DOI:10.1016/j.vaccine.2014.07.111 · 3.62 Impact Factor
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