DNA Vaccine Carrier Research Articles

RGDK-lipopeptide for targeting genetic vaccines to antigen presenting cells

Transfection into antigen presenting cells (APCs) is a challenging task in DNA/m-RNA vaccination. Mannose receptor (overexpressed in DCs) selective liposomes containing shikimoyl and quionoic head groups were reported earlier for delivering antigen-encoded plasmid DNA to DCs in vivo. Although APCs also have integrin receptors but there is not much report. Herein, we report the integrin receptor selective liposomes of RGDK-lipopeptide I can deliver pCMV-GFP in RAW 264.7 cells (mouse macrophages cells). We also notice more that presence of endosome disrupting histidinylated lipid II increases the transfection efficiency of the liposomes of RGDK-lipopeptide I in RAW 264.7 cells. Future applications of this liposomal DNA vaccine carrier is expected in the development of efficient vaccinations against a variety of infectious illnesses and malignancies.

Advancement in Polymer-based Carrier for DNA Vaccine.

A novel strategy that has the potential to solve the drawbacks of the present conventional vaccines is the development of DNA vaccines. DNA vaccines offer a versatile and adaptable platform for treating a wide variety of diseases, as immunization targets may be easily adjusted by altering the gene sequences encoded in the plasmid DNA delivered. Due to their ability to elicit both humoral and cellular immune responses, their stability, and the ease with which they may be produced, plasmid DNA vaccines are quickly becoming the vaccine of choice, they are frequently safer than conventional vaccinations. Despite the highly encouraging outcomes of ongoing clinical trials, these vaccines' immunogenicity is compromised by a few factors. The use of various vaccine delivery techniques, the use of various polymer-based carriers, and the use of adjuvants are some of the several approaches that might be examined to better the immunogenicity of DNA vaccines made from plasmids. These advancements taken together might allow plasmid DNA vaccines to be successfully used in clinical settings.

Mannose-modified erythrocyte membrane-encapsulated chitovanic nanoparticles as a DNA vaccine carrier against reticuloendothelial tissue hyperplasia virus.

The erythrocyte membranes used in nanovaccines include high membrane stability, long circulation life, adaptability and extremely good bio compatibility. Nanoparticles encapsulated by erythrocyte membranes are widely used as ideal drug delivery vehicles because of their high drug loading, long circulation time, and excellent biocompatibility. The mannose modification of delivery materials can help target mannose receptors (MRs) to deliver antigens to antigen-presenting cells (APCs). In this study, the antigen gene gp90 of avian reticuloendotheliosis virus (REV) was encapsulated with carboxymethyl chitosan (CS) to obtain CSgp90 nanoparticles, which were coated with mannose-modied fowl erythrocyte membranes to yield CS-gp90@M-M nanoparticles. The physicochemical characterization and immune response of the CS-gp90@M-M nanoparticles were investigated in vitro and in vivo. CS-gp90@M-M nanoparticles were rapidly phagocytized in vitro by macrophages to induce the production of cytokines and nitric oxide. In vivo, CS-gp90@M-M nanoparticles increased cytokine levels, the CD4+/8+ ratio, REV-specific antibodies in the peripheral blood of chicks, and the mRNA levels of immune-related genes in the spleen and bursa of immunized chicks. CS-gp90@M-M nanoparticles could be targeted to lymphoid organs to prolong the retention time of the nanoparticles at the injection site and lymphatic organs, leading to a strong, sustained immune response. Moreover, the CS-gp90@M-M nano-vaccine showed a lasting immunoprotective effect and improved the body weight of chicks after the challenge. Overall, CS-gp90@M-M nanoparticles can be used in vaccine designs as an effective delivery carrier with immune response-enhancing effects.

Mannose functionalized biomimetic nanovaccine enhances immune responses against tilapia lake virus

Tilapia lake virus disease (TiLVD) caused by tilapia lake virus (TiLV) is a lethality truculence viral disease endangering the sustainable development of tilapia aquaculture. DNA vaccine present immense application potential in disease prevention and control, but the low gene transfection efficacy of naked DNA vaccine imposes restrictions on itself immune response that should have been induced. In this study, we constructed a biomimetic nanodelivery system (Cs-pS2@M-M) using the mannose modified erythrocyte membrane acted as a DNA vaccine carrier. The nanoparticle has a typical core-shell structure with a particle size of ~100 nm, and ensures sustained and efficient expression of plasmid DNA in muscle and spleen tissue. Intramuscular immunization of tilapia to evaluate the efficacy of the vaccine, the results showed that it has a high-effective induction of serum antibody production, enzyme activity, and immune-related gene expression compared to the same dose (10 μg/g) of non-mannosylated Cs-pS2@M nanoparticles and naked DNA vaccine. Notably, the TiLV challenge trial show that Cs-pS2@M-M provided 76.9% relative percentage survival (RPS), which was 26.9% higher than the 50.0% of the naked DNA vaccine (pS2), and not only that, it was 15.4% higher than that of Cs-pS2@M without mannose modification. These results showed that Cs-pS2@M-M biomimetic nanovaccine constructed in this study elicited robust immune responses to protect tilapia from TiLV challenge, and erythrocyte membrane-coated nanoparticles strategy show enormous promise potential as a vaccine delivery platform for aquatic animals.

Intranasal immunization with O-2\u2032-Hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles loaded with Newcastle disease virus DNA vaccine enhances mucosal immune response in chickens

BackgroundThere has been a great interest in developing strategies for enhancing antigen delivery to the mucosal immune system as well as identifying mucosal active immunostimulating agents. To elevate the potential of O-2ʹ-Hydroxypropyl trimethyl ammonium chloride chitosan (O-2ʹ-HACC) as an adjuvant and mucosal immune delivery carrier for DNA vaccine, we prepared the O-2ʹ-HACC loaded with Newcastle disease virus (NDV) F gene plasmid DNA and C3d6 molecular adjuvant (O-2ʹ-HACC/pFDNA microparticles).ResultsThe O-2ʹ-HACC/pFDNA exhibited a regular spherical morphology with a particle size of 202.3 ± 0.52 nm, a zeta potential of 50.8 ± 8.21 mV, encapsulation efficiency of 90.74 ± 1.10%, and a loading capacity of 49.84 ± 1.20%. The plasmid DNA could be sustainably released from the O-2ʹ-HACC/pFDNA after an initial burst release. Intranasal vaccination of chickens immunized with O-2ʹ-HACC/pFDNA not only induced higher anti-NDV IgG and sIgA antibody titers but also significantly promoted lymphocyte proliferation and produced higher levels of IL-2, IL-4, IFN-γ, CD4+, and CD8 + T lymphocytes compared with the NDV commercial live attenuated vaccine. Intranasal delivery of the O-2ʹ-HACC/pFDNA enhanced humoral, cellular, and mucosal immune responses and protected chickens from the infection of highly virulent NDV compared with the intramuscular delivery.ConclusionsCollectively, our findings indicated that the O-2ʹ-HACC could be used as a vaccine adjuvant and delivery system for mucosal immunity and have an immense application promise.Graphic

Immersion immunization of koi (Cyprinus carpio) against cyprinid herpesvirus 3 (CyHV-3) with carbon nanotube-loaded DNA vaccine

Koi as a popular ornamental fish were threatened by the emergence of a deadly disease caused by cyprinid herpesvirus 3 (CyHV-3; initially called koi herpesvirus or KHV), while there is no effective drug or vaccine against this fatal disease at present. Meanwhile, many drugs and vaccines had no effect in many cases account of several impenetrable barriers (cell, skin and gastrointestinal tract). Here we reported an immersion DNA vaccine system encoding a plasmid (pcDNA) coupled with ORF149 gene of KHV based on single-walled carbon nanotubes (SWCNTs). To evaluate its efficacy against KHV, we set 9 different treatment groups contained PBS, pcDNA3.1 vector, inactivated virus, 1, 5, 10 mg/L of pcDNA3.1-ORF149, 1, 5, 10 mg/L of SWCNTs-pcDNA3.1-ORF149. The juvenile koi fish (3.0 ± 1.0 g) was vaccinated via immersion (100 fish per tank with 8 L rearing water). We found a stronger and longer duration immune response (serum antibody production, enzyme activities and immune-related genes expression) can be induced in fish vaccinated with high concentration SWCNTs-p149 in comparison with those vaccinated with p149 alone. The vaccine conferred an 56% protection against intraperitoneal challenge with 50 μL dose live KHV virus (7.3 × 105 TCID50/mL), which is the highest in the experiment. Thereby, this study demonstrates that SWCNTs as a promising carrier for DNA vaccine against KHV might be used to vaccinate large-scale juvenile koi fish by bath administration approach, which will effectively alleviate the pressure of the severe situation of KHV control.

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

The Lactococcus lactis bacterium found in different natural environments is traditionally associated with the fermented food industry. But recently, its applications have been spreading to the pharmaceutical industry, which has exploited its probiotic characteristics and is moving towards its use as cell factories for the production of added-value recombinant proteins and plasmid DNA (pDNA) for DNA vaccination, as a safer and industrially profitable alternative to the traditional Escherichia coli host. Additionally, due to its food-grade and generally recognized safe status, there have been an increasing number of studies about its use in live mucosal vaccination. In this review, we critically systematize the plasmid replicons available for the production of pharmaceutical-grade pDNA and recombinant proteins by L. lactis. A plasmid vector is an easily customized component when the goal is to engineer bacteria in order to produce a heterologous compound in industrially significant amounts, as an alternative to genomic DNA modifications. The additional burden to the cell depends on plasmid copy number and on the expression level, targeting location and type of protein expressed. For live mucosal vaccination applications, besides the presence of the necessary regulatory sequences, it is imperative that cells produce the antigen of interest in sufficient yields. The cell wall anchored antigens had shown more promising results in live mucosal vaccination studies, when compared with intracellular or secreted antigens. On the other side, engineering L. lactis to express membrane proteins, especially if they have a eukaryotic background, increases the overall cellular burden. The different alternative replicons for live mucosal vaccination, using L. lactis as the DNA vaccine carrier or the antigen producer, are critically reviewed, as a starting platform to choose or engineer the best vector for each application.

Biopolymer‐based Carriers for DNA Vaccine Design

AbstractOver the last 30 years, genetically engineered DNA has been tested as novel vaccination strategy against various diseases, including human immunodeficiency virus (HIV), hepatitis B, several parasites, and cancers. However, the clinical breakthrough of the technique is confined by the low transfection efficacy and immunogenicity of the employed vaccines. Therefore, carrier materials were designed to prevent the rapid degradation and systemic clearance of DNA in the body. In this context, biopolymers are a particularly promising DNA vaccine carrier platform due to their beneficial biochemical and physical characteristics, including biocompatibility, stability, and low toxicity. This article reviews the applications, fabrication, and modification of biopolymers as carrier medium for genetic vaccines.

Biopolymer-based Carriers for DNA Vaccine Design.

Over the last 30 years, genetically engineered DNA has been tested as novel vaccination strategy against various diseases, including human immunodeficiency virus (HIV), hepatitis B, several parasites, and cancers. However, the clinical breakthrough of the technique is confined by the low transfection efficacy and immunogenicity of the employed vaccines. Therefore, carrier materials were designed to prevent the rapid degradation and systemic clearance of DNA in the body. In this context, biopolymers are a particularly promising DNA vaccine carrier platform due to their beneficial biochemical and physical characteristics, including biocompatibility, stability, and low toxicity. This article reviews the applications, fabrication, and modification of biopolymers as carrier medium for genetic vaccines.

Lipofection-Based Delivery of DNA Vaccines.

The preventive and therapeutic potential of DNA vaccines combined with benefits of lipid-based delivery (lipofection) allow efficient nucleic acid transfer and immunization applicable in treatment of infections, cancer or autoimmune disorders. Lipofecting compositions consisting of cationic and neutral lipids can be used for both in vitro and in vivo applications and may also play the role of adjuvants. Here we describe a simple protocol of DNA vaccine carrier preparation based on cationic polyprenyl derivatives (PTAI-trimethylpolyprenylammonium iodides) and commonly used helper lipids with use of basic laboratory equipment. Such formulas have proven effective for immunization of animals as well as for cell transfection.

Enhanced protective immune response of foot-and-mouth disease vaccine through DNA-loaded virus-like particles

Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects cloven-hoofed animals. Virus-like particles (VLPs) can induce a robust immune response and deliver DNA and small molecules. In this study, a VLP-harboring pcDNA3.1/P12A3C plasmid was generated, and the protective immune response was characterized. Guinea pigs were injected with VLPs, naked DNA vaccine, DNA-loaded VLPs, or phosphate-buffered saline twice subcutaneously at four-week intervals. Results demonstrated that the VLPs protected the naked DNA from DNase degeneration and delivered the DNA into the cells in vitro. The DNA-loaded VLPs and the VLPs alone induced a similar level of specific antibodies (P > 0.05) except at 49 dpv (P < 0.05). The difference in interferon-γ was consistent with that in specific antibodies. The levels of neutralizing antibodies induced by the DNA-loaded VLPs were significantly higher than those of other samples (P < 0.01). Similarly, the lymphocyte proliferation by using DNA-loaded VLPs was significantly higher than those using other formulas after booster immunization. Vaccination with DNA-loaded VLPs provided higher protection (100%) against viral challenge compared with vaccination with VLPs (75%) and DNA vaccine (25%). This study suggested that VLPs can be used as a delivery carrier for DNA vaccine. In turn, the DNA vaccine can enhance the immune response and prolong the serological duration of the VLP vaccine. This phenomenon contributes in providing complete protection against the FMDV challenge in guinea pigs and can be valuable in exploring novel nonreplicating vaccines and controlling FMD in endemic countries worldwide.

Vitamin E Scaffolds of pH-Responsive Lipid Nanoparticles as DNA Vaccines in Cancer and Protozoan Infection

DNA vaccinations are promising strategies for treating diseases that require cellular immunity (i.e., cancer and protozoan infection). Here, we report on the use of a liposomal nanocarrier (lipid nanoparticles (LNPs)) composed of an SS-cleavable and pH-activated lipidlike material (ssPalm) as an in vivo DNA vaccine. After subcutaneous administration, the LNPs containing an ssPalmE, an ssPalm with vitamin E scaffolds, elicited a higher gene expression activity in comparison with the other LNPs composed of the ssPalms with different hydrophobic scaffolds. Immunization with the ssPalmE-LNPs encapsulating plasmid DNA that encodes ovalbumin (OVA, a model tumor antigen) or profilin (TgPF, a potent antigen of Toxoplasma gondii) induced substantial antitumor or antiprotozoan effects, respectively. Flow cytometry analysis of the cells that had taken up the LNPs in draining lymph nodes (dLNs) showed that the ssPalmE-LNPs were largely taken up by macrophages and a small number of dendritic cells. We found that the transient deletion of CD169+ macrophages, a subpopulation of macrophages that play a key role in cancer immunity, unexpectedly enhanced the activity of the DNA vaccine. These data suggest that the ssPalmE-LNPs are effective DNA vaccine carriers, and a strategy for avoiding their being trapped by CD169+ macrophages will be a promising approach for developing next-generation DNA vaccines.

Single-walled carbon nanotubes as delivery vehicles enhance the immunoprotective effect of an immersion DNA vaccine against infectious spleen and kidney necrosis virus in mandarin fish

As a high mortality disease, Infectious spleen and kidney necrosis virus (ISKNV) can cause massive economic damage on mandarin fish farming industry in China, which seriously hindered the development of mandarin fish farming industry. In this research, SWCNTs (single-walled carbon nanotubes) as a candidate for DNA vaccine carrier was vaccinated by immersion (1, 2, 5, 10, 20 mg/L) in juvenile mandarin fish. In muscle, spleen and kidney tissues, the results showed that transcription and expression of MCP gene can be detected in pcDNA-MCP and SWCNTs-pcDNA-MCP groups after bath immunization. The immune response (immune-related genes expression, serum antibody production, enzyme activities and C3 content) was significantly enhanced in fish which vaccinated with SWCNTs-pcDNA-MCP in comparison with those vaccinated with pcDNA-MCP alone. After 14 d challenge, the RPS (relative percentage survival) can be enhanced which using SWCNTs as a carrier in SWCNTs-pcDNA-MCP (82.4%) group at 20 mg/L (the highest vaccine dose) than the naked pcDNA-MCP (54.2%) group. This study reveals that functionalized SWCNTs could be a promising immersion DNA vaccine carrier in aquaculture.

Evaluation of immune response and protection against spring viremia of carp virus induced by a single-walled carbon nanotubes-based immersion DNA vaccine

Spring viremia of carp virus (SVCV) has caused mass mortality in cyprinids, with case fatality rates of young fish up to 90%, resulting in enormous economic losses in the aquaculture industry. Immersion vaccination is considered as the most effective method for juvenile fish to combating disease, due to its convenience for mass vaccination and stress-free administration. However, immune responses following immersion vaccination are generally less robust and of shorter duration as those induced through intraperitoneal injection. Herein, to enhance the efficient of immersion vaccine, functionalized single-walled carbon nanotubes (SWCNTs) as carrier were used to manufacture immersion DNA vaccine system (SWCNTs-pEGFP-M) with chemical modification. Results showed that SWCNTs-pEGFP-M could enter into fish body via immersion administration and express antigen proteins in fish kidney and spleen. Moreover, stronger and longer duration immune responses (including serum antibody production and immune genes expression) can be induced in fish vaccinated with SWCNTs-pEGFP-M in comparison with those vaccinated with pEGFP-M alone. Notably, SWCNTs can increase the immune protective effect of naked DNA vaccine by ca. 23.8%. Altogether, this study demonstrates that SWCNTs as a promising DNA vaccine carrier might be used to vaccinate large-scale juvenile fish by bath administration approach, which can provide an outlook for future vaccination strategies against SVCV.

Self-destructing Salmonella via temperature induced gene E of phage PhiX174 improves influenza HA DNA vaccine immune protection against H1N1 infection in mice model

The delivery of DNA vaccines is the principle impediment for implementation of DNA vaccination on a mass scale. In this study, we report a temperature induced conditionally expressed phage PhiX174 gene E mediated lysis of Salmonella under in vivo conditions that can increase the immunogenicity of a DNA vaccine delivered via Salmonella carrier system. We electroporated gene E encoding lysis plasmid pJHL187 along with the pcDNA-HA plasmid encoding H1N1 HA into attenuated Salmonella Typhimurium, strain JOL1893. Using C57BL/6 mice as the model, we showed that the mice intragastrically vaccinated with JOL1893 induced significant production of HA-specific humoral and cell mediated immune responses compared to the JOL1837, which carry pcDNA-HA plasmid alone. Furthermore, mice vaccinated with JOL1893 vaccine were fully protected against the lethal H1N1 challenge compared to the JOL1837 strain, which showed 90% protection only. However, none of the animals survived treated with either the PBS or the Salmonella carrying empty vector. Taken together, our results indicate that mucosal immunization with conditional lysis enabled live attenuated S. Typhimurium as a DNA vaccine carrier can induce efficient systemic and mucosal immune responses, and improves immune protection against a highly pathogenic H1N1 infection in mice model.

Bacterial ghost as delivery vehicles loaded with DNA vaccine induce significant and specific immune responses in common carp against spring viremia of carp virus

Although vaccine is a prophylaxis measure for the contagious and fatal disease caused by spring viremia of carp virus (SVCV), until now, no commercial vaccine is available for worldwide use. To find more effective and safe means for the control of SVCV infection, here, an Escherichia coli DH5α bacterial ghost (DH5α-BG, non-living bacterial) based DNA vaccine delivery system (BG/pEG-G) was constructed. Carp were injected intramuscularly by different treatments (PBS, pEGFP, BG, pEG-G and BG/pEG-G), and the immunoprotective effect induced by these treatments were analyzed. We found a stronger and longer duration immune response (serum antibody production and immune-related genes expression) can be induced in fish vaccinated with BG/pEG-G in comparison with those vaccinated with pEG-G alone. Additionally, a good immune protective effect (relative percentage survival >81.48%) was observed in fish vaccinated with BG/pEG-G vaccine at the dose of 0.2 μg DNA/g of fish. Overall, this study for the first time demonstrates the ability of DH5α-BG as DNA vaccine carrier against SVCV infection in carps, suggesting a practical multivalent strategy for the control of aquatic disease.

In vivo targeting of DNA vaccines to dendritic cells using functionalized gold nanoparticles.

The clinical success of dendritic cell (DC)-based genetic immunization remains critically dependent on the availability of effective and safe nano-carriers for targeting antigen-encoded DNA vaccines to DCs, the most potent antigen-presenting cells in the human body in vivo. Recent studies revealed the efficacies of mannose receptor-mediated in vivo DC-targeted genetic immunization by liposomal DNA vaccine carriers containing both mannose-mimicking shikimoyl and transfection enhancing guanidinyl functionalities. However, to date, the efficacies of this approach have not been examined for metal-based nanoparticle DNA vaccine carriers. Herein, we report for the first time, the design, synthesis, physico-chemical characterization and bioactivities of gold nanoparticles covalently functionalized with a thiol ligand containing both shikimoyl and guanidinyl functionalities (Au-SGSH). We show that Au-SGSH nanoparticles can deliver DNA vaccines to mouse DCs under in vivo conditions. Subcutaneous administration of near infrared (NIR) dye-labeled Au-SGSH showed significant accumulation of the NIR dye in the DCs of the nearby lymph nodes compared to that for the non-targeting NIR-labeled Au-GSH nanoconjugate containing only a covalently tethered guanidinyl group, not the shikimoyl-functionality. Under prophylactic settings, in vivo immunization (s.c.) with the Au-SGSH-pCMV-MART1 nanoplex induced a long-lasting (180 days) immune response against murine melanoma. Notably, mannose receptor-mediated in vivo DC-targeted immunization (s.c.) with the Au-SGSH-MART1 nanoplex significantly inhibited established melanoma growth and increased the overall survivability of melanoma-bearing mice under therapeutic settings. The Au-SGSH nanoparticles reported herein have potential use for in vivo DC-targeted genetic immunization against cancer and infectious diseases.

Oral yeast-based DNA vaccine confers effective protection from Aeromonas hydrophila infection on Carassius auratus

Our previous study has demonstrated that recombinant yeast can induce specific immune responses in Carassius auratus and may serve as a potential carrier for oral DNA vaccines in aquaculture. In this study, we further developed an effective yeast-based oral DNA vaccine against the bacteria Aeromonas hydrophila, which was expected to provide protection from the motile aeromonad septicemia (MAS). First, two candidate antigen genes, ompG and omp48, were cloned from the Aeromonas hydrophila genome DNA. Then, relative yeast-eukaryote shuttle vectors were constructed and their expression in eukaryotes was validated. Next, crucian carps were orally administered with ompG or omp48 recombinant yeast, and the expression of the genes in the intestinal mucosa was confirmed by immunohistochemistry (IHC). The specific immune responses were further detected by Western blot and enzyme-linked immunosorbent assay (ELISA). The ELISA results showed that the production of the OVA-specific antibody in the OVA-ompG group was significantly higher than that of the OVA-omp48 group, indicating that the OVA-ompG group elicited obviously stronger immune response than OVA-omp48. Finally, the challenge experiment against Aeromonas hydrophila infection demonstrated decreased fish mortality rate after the oral administration of the OVA-ompG yeast vaccine. In conclusion, our work provided a framework for the further development of oral yeast-based fishery vaccines.

Immune response and protective effect against spring viremia of carp virus induced by intramuscular vaccination with a SWCNTs-DNA vaccine encoding matrix protein

To elicit the immune protective of vaccine against the highly contagious and pathogenic disease caused by spring viremia of carp virus (SVCV), a novel functionalized single-walled carbon nanotubes (SWCNTs) were applied as a delivery vehicle for DNA vaccine. In this study, we report a SWCNTs-DNA vaccine encoding matrix protein of SVCV which, when injected in the muscle at a dose of 10 μg SWCNTs-pcDNA-M vaccine, confers up to 51.3% protection against intraperitoneal challenge with SVCV. In addition, SWCNTs as a promising vehicle can enhance about 17.5% of the immune protective effect in SWCNTs-pcDNA-M vaccinated common carp compared with fish injected with naked pcDNA-M DNA vaccine. In addition, serum antibody production, none specific immunity parameters (complement activity, superoxide dismutase activity (SOD), acid phosphatase activity (ACP) and alkaline phosphatase activity (AKP)) and immune-related genes were used to verify the enhancement immune response induced in SWCNTs-pcDNA-M vaccinated fish, herein all these mentioned immune activities were significantly enhanced after immunization. Thereby, it is revealed that the M gene of SVCV could be used as an antigen for DNA vaccine constructs, and SWCNTs could be a candidate DNA vaccine carrier to enhance the immunological response against fish disease.

Live Bacterial Vectors-A Promising DNA Vaccine Delivery System.

Vaccination is one of the most successful immunology applications that has considerably improved human health. The DNA vaccine is a new vaccine being developed since the early 1990s. Although the DNA vaccine is promising, no human DNA vaccine has been approved to date. The main problem facing DNA vaccine efficacy is the lack of a DNA vaccine delivery system. Several studies explored this limitation. One of the best DNA vaccine delivery systems uses a live bacterial vector as the carrier. The live bacterial vector induces a robust immune response due to its natural characteristics that are recognized by the immune system. Moreover, the route of administration used by the live bacterial vector is through the mucosal route that beneficially induces both mucosal and systemic immune responses. The mucosal route is not invasive, making the vaccine easy to administer, increasing the patient’s acceptance. Lactic acid bacterium is one of the most promising bacteria used as a live bacterial vector. However, some other attenuated pathogenic bacteria, such as Salmonella spp. and Shigella spp., have been used as DNA vaccine carriers. Numerous studies showed that live bacterial vectors are a promising candidate to deliver DNA vaccines.