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      Strategies and hurdles using DNA vaccines to fish

      review-article
      1 , 2 , 1 ,
      Veterinary Research
      BioMed Central

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          Abstract

          DNA vaccinations against fish viral diseases as IHNV at commercial level in Canada against VHSV at experimental level are both success stories. DNA vaccination strategies against many other viral diseases have, however, not yet yielded sufficient results in terms of protection. There is an obvious need to combat many other viral diseases within aquaculture where inactivated vaccines fail. There are many explanations to why DNA vaccine strategies against other viral diseases fail to induce protective immune responses in fish. These obstacles include: 1) too low immunogenicity of the transgene, 2) too low expression of the transgene that is supposed to induce protection, 3) suboptimal immune responses, and 4) too high degradation rate of the delivered plasmid DNA. There are also uncertainties with regard distribution and degradation of DNA vaccines that may have implications for safety and regulatory requirements that need to be clarified. By combining plasmid DNA with different kind of adjuvants one can increase the immunogenicity of the transgene antigen – and perhaps increase the vaccine efficacy. By using molecular adjuvants with or without in combination with targeting assemblies one may expect different responses compared with naked DNA. This includes targeting of DNA vaccines to antigen presenting cells as a central factor in improving their potencies and efficacies by means of encapsulating the DNA vaccine in certain carriers systems that may increase transgene and MHC expression. This review will focus on DNA vaccine delivery, by the use of biodegradable PLGA particles as vehicles for plasmid DNA mainly in fish.

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          Most cited references85

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          DNA vaccines: an historical perspective and view to the future.

          Aiqin Liu (2010)
          This review provides a detailed look at the attributes and immunologic mechanisms of plasmid DNA vaccines and their utility as laboratory tools as well as potential human vaccines. The immunogenicity and efficacy of DNA vaccines in a variety of preclinical models is used to illustrate how they differ from traditional vaccines in novel ways due to the in situ antigen production and the ease with which they are constructed. The ability to make new DNA vaccines without needing to handle a virulent pathogen or to adapt the pathogen for manufacturing purposes demonstrates the potential value of this vaccine technology for use against emerging and epidemic pathogens. Similarly, personalized anti-tumor DNA vaccines can also readily be made from a biopsy. Because DNA vaccines bias the T-helper (Th) cell response to a Th1 phenotype, DNA vaccines are also under development for vaccines against allergy and autoimmune diseases. The licensure of four animal health products, including two prophylactic vaccines against infectious diseases, one immunotherapy for cancer, and one gene therapy delivery of a hormone for a food animal, provides evidence of the efficacy of DNA vaccines in multiple species including horses and pigs. The size of these target animals provides evidence that the somewhat disappointing immunogenicity of DNA vaccines in a number of human clinical trials is not due simply to the larger mass of humans compared with most laboratory animals. The insights gained from the mechanisms of protection in the animal vaccines, the advances in the delivery and expression technologies for increasing the potency of DNA vaccines, and encouragingly potent human immune responses in certain clinical trials, provide insights for future efforts to develop DNA vaccines into a broadly useful vaccine and immunotherapy platform with applications for human and animal health. © 2010 John Wiley & Sons A/S.
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            Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination.

            The demand is currently high for new vaccination strategies, particularly to help combat problematic intracellular pathogens, such as HIV and malarial parasites. In the past decade, the identification of host receptors that recognize pathogen-derived nucleic acids has revealed an essential role for nucleic acid sensing in the triggering of immunity to intracellular pathogens. This Review first addresses our current understanding of the nucleic acid-sensing immune machinery. We then explain how the study of nucleic acid-sensing mechanisms not only has revealed their central role in driving the responses mediated by many current vaccines, but is also revealing how they could be harnessed for the design of new vaccines.
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              Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome.

              Many currently used and candidate vaccine adjuvants are particulate in nature, but their mechanism of action is not well understood. Here, we show that particulate adjuvants, including biodegradable poly(lactide-co-glycolide) (PLG) and polystyrene microparticles, dramatically enhance secretion of interleukin-1beta (IL-1beta) by dendritic cells (DCs). The ability of particulates to promote IL-1beta secretion and caspase 1 activation required particle uptake by DCs and NALP3. Uptake of microparticles induced lysosomal damage, whereas particle-mediated enhancement of IL-1beta secretion required phagosomal acidification and the lysosomal cysteine protease cathepsin B, suggesting a role for lysosomal damage in inflammasome activation. Although the presence of a Toll-like receptor (TLR) agonist was required to induce IL-1beta production in vitro, injection of the adjuvants in the absence of TLR agonists induced IL-1beta production at the injection site, indicating that endogenous factors can synergize with particulates to promote inflammasome activation. The enhancement of antigen-specific antibody production by PLG microparticles was independent of NALP3. However, the ability of PLG microparticles to promote antigen-specific IL-6 production by T cells and the recruitment and activation of a population of CD11b(+)Gr1(-) cells required NALP3. Our data demonstrate that uptake of microparticulate adjuvants by DCs activates the NALP3 inflammasome, and this contributes to their enhancing effects on innate and antigen-specific cellular immunity.
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                Author and article information

                Contributors
                Journal
                Vet Res
                Vet. Res
                Veterinary Research
                BioMed Central
                0928-4249
                1297-9716
                2014
                19 February 2014
                : 45
                : 1
                : 21
                Affiliations
                [1 ]UiT - The Arctic University of Norway, Faculty of Biosciences, Fisheries & Economics, Norwegian College of Fishery Science 9037 Tromsø, Norway
                [2 ]Genøk – Centre for Biosafety, The Science Park, Postbox 6418, 9294 Tromsø Norway
                Article
                1297-9716-45-21
                10.1186/1297-9716-45-21
                3942184
                24552235
                6bb0cab0-f726-465e-ab20-59d83d535588
                Copyright © 2014 Hølvold et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 10 July 2013
                : 5 February 2014
                Categories
                Review

                Veterinary medicine
                Veterinary medicine

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