Dna Vaccines: New Applications for Veterinary Medicine

Topics: Immune system, Vaccine, Vaccination Pages: 40 (13863 words) Published: September 9, 2013
DNA vaccines: new applications for veterinary medicine
Vinciane Dufour Service de Biologie Moleculaire, Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Ploufragan, Brittany, France

Introduction
In 1990, Wolff and his colleagues were the first to report the successful expression of naked plasmid DNA in mouse muscle tissue [108]. A few years later it was reported that the injection of DNA encoding an antigenic protein of influenza virus conferred protective immunity in mice [97]. Many papers have described and reviewed the protective immunity induced by DNA against a large variety of viruses [20], bacteria [90] and protozoa [47] in murine models. DNA immunisation has also been investigated for the treatment of cancer [6] and autoimmune diseases [72]. Trials are now being developed for human DNA vaccines against several diseases such as AIDS and malaria [96, 104]. The administration of a simple plasmid can induce a broad spectrum of immune responses [54]. They include the activation of CD8+ T lymphocytes, implicated in host defense against intracellular pathogens via cytotoxic T lymphocytes (CTL), and CD4+ T lymphocytes, which secrete cytokines and play a role in B cell production of specific antibodies (Figure 1). Despite its potential impact on protective immunity, however, DNA vaccination is not always successful. Protective immunity depends mostly on the immunogenicity of a pathogen’s antigen, but other factors such as the frequency and route of administration, the amount of DNA, the localisation of the plasmid codedantigen (secreted, membrane-bound or cytoplasmic), and the age, health and species of the animals vaccinated, have an affect.

Principle and advantages
Characteristics of the expression vectors The first vectors used for DNA vaccination were bacterial plasmids, developed originally for the in vitro expression of foreign protein in mammalian cells [28]. A plasmid contains a prokaryotic replication origin that allows high-yield production in bacteria, and an antibiotic resistance gene for selective growing. The transcriptional unit carries a viral promoter that may lead to constitutive expression in a wide variety of cells (Figure 1). The human cytomegalovirus immediate early (HCMVie) enhancer/promoter. Rous sarcoma virus long terminal repeat (RSV-LTR) are often used. Antigen expression is increased when an untranslated region, with its splicing signals, follows the promoter. The sequence encoding the antigen is 3’ -flanked by the transcript termination/polyadenylation (polyA) signal of the SV40 or of the bovine growth hormone (BGH). The plasmid pcDNA3 and its derivatives, which contain the HCMVie promoter and the BGH polyA, have often been used as vectors for DNA vaccines.

© Veterinary Sciences Tomorrow - Issue 2 - April 2001

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Figure 1. Principle of DNA vaccination. Production of a genetic vaccine involves the isolation of genes from a selected pathogen followed by their insertion into a mammalian expression plasmid. After large-scale production and purification steps, the DNA vaccine is usually delivered to animals by intramuscular (i.m.) injection. The mechanisms by which the antigen is produced (by myocytes, keratinocytes, MHC II-negative cells or professional antigen-presenting cells), processed and presented to the immune system are still disputed. However, following the processes of antigen production and processing, pathogen-derived peptides are presented by MHC I and MHC II molecules to induce cellular and humoral immune responses.

© Veterinary Sciences Tomorrow - Issue 2 - April 2001

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Advantages Production and storage: Antigen-expressing plasmids are amplified in bacterial cultures, making the production of DNA vaccines easy, rapid and economical. Bacterial production of plasmid DNA also avoids the risk of potential contamination with the viruses/proteins present in eukaryotic cell lines used to produce conventional vaccines. In addition, plasmid DNA molecules...
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