DNA Vaccines

Fish & Shellfish Immunology (2008) 25,1e18 available at www.sciencedirect.comjournal homepage: www.elsevier.com/locate/fsi REVIEW What happens to the DNA vaccine in fish? A review of current knowledgeTom Christian Tonheim* , Jarl Bøgwald, Roy
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DNA VaccinesFish & Shellfish Immunology (2008) 25,1e18 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/fsiREVIEW What happens to the DNA vaccine in fish? A review of current knowledgeTom Christian Tonheim * , Jarl Bøgwald, Roy Ambli Dalmo **Department of Marine Biotechnology, The Norwegian College of Fishery Science,University of Tromsø, N-9037 Tromsø, NorwayReceived 12 November 2007; revised 11 March 2008; accepted 12 March 2008Available online 19 March 2008 KEYWORDS Abstract The primary function of DNA vaccines, a bacterial plasmid DNA containing a con- DNA vaccine; struct for a given protective antigen, is to establish specific and long-lasting protective immu- Fish; nity against diseases where conventional vaccines fail to induce protection. It is acknowledged Tissue distribution; that less effort has been made to study the fate, in terms of cellular uptake, persistence and Plasmid DNA receptors degradation, of DNA vaccines after in vivo administration. However, during the last year some papers have given new insights into the fate of DNA vaccines in fish. By comparing the newly acquired information in fish with similar knowledge from studies in mammals, similarities with regard to transport, blood clearance, cellular uptake and degradation of DNA vaccines have been found. But the amount of DNA vaccine redistributed from the administration site after intramuscular administration seems to differ between fish and mammals. This review presents up-to-date and in-depth knowledge concerning the fate of DNA vaccines with emphasis on tis- sue distribution, cellular uptake and uptake mechanism(s) before finally describing the intra- cellular hurdles that DNA vaccines need to overcome in order to produce their gene product. ª 2008 Elsevier Ltd. All rights reserved.DNA vaccines capable of being replicated autonomously in prokaryotes. Plasmid DNA used in gene delivery studies normallyA plasmid DNA (pDNA) is often used as a vehicle for gene contains promoter- and enhancer sequences, the gene ofdelivery to mammals and fish. The pDNA is a circular interest, a poly-adenylation sequence, transcriptionalmolecule consisting of double-stranded deoxyribonucleic termination sequence, antibiotic resistance gene and originacid (DNA, not different from chromosomal DNA), usually of replication. To express the gene of interest, pDNA is transcribed and mRNA is translated to protein by the cell’s own apparatus. This opens up the applicability of pDNA in * Corresponding author. Tel.: þ47 77 6460 22; fax: þ4777 64 6020. two important areas: gene therapy and DNA vaccination. ** Corresponding author. Tel.: þ47 776444 82; fax: þ47 77 64 6020. The definition of gene therapy and DNA vaccines is not E-mail addresses:tom.tonheim@nfh.uit.no(T.C. Tonheim),oy. r consistent in the literature. Often, gene therapy alsodalmo@nfh.uit.no(R.A. Dalmo). encompasses the use of DNA vaccines. The Norwegian1050-4648/$ - see front matter ª 2008 Elsevier Ltd. All rights reserved.doi:10.1016/j.fsi.2008.03.0072 T.C. Tonheim et al.Biotechnology Advisory Board ( www.bion.no ) defines gene lymphocytes [29]. In fish, the different subsets of T cellstherapy in animals as the intentional transfer of genetic are not well characterised, but CD8 [23,30e32] and CD4material to somatic cells for purposes other than in uenc- [33e35] homologues are reported. Genes of MHC class IIbing the immune system [1]. Gene therapy is often aimed [36e38] and MHC class I gene [39] are found, and genesto achieve a long-lasting physiologically matched expres- involved in MHC class I [40] and class II [41] loading path-sion of the gene, without activating the immune system. ways are described in fish. Only three classes of immuno-In contrast, DNA vaccination is defined as the intentional globulins; IgM [42e46] , IgD [47e54] and IgZ/IgT [55,56]transfer of genetic material to somatic cells for the are reported in fish, but there are no indications that thispurposes of in uencing the immune system [1] . For DNA repertoire of immunoglobulins are functionally retardedvaccination, a short-term expression is sufficient for evok- in any waydbesides the absence of, e.g., IgG, IgA and IgEing an immune response. in fish. Immune responses are harder to investigate in fishWorking mechanism of DNA vaccines compared to mammals, due to lack of tools (e.g. cell lines, gene sequences, markers and antibodies). However,The immune response afte ...