DNA vaccines: A safe and efficient platform technology for responding to emerging infectious diseases

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Heath, Bethesda, MD 20892, USA.
Human vaccines (Impact Factor: 3.64). 09/2009; 5(9):623-6. DOI: 10.4161/hv.8627
Source: PubMed

ABSTRACT Traditionally vaccines are based on immunogens delivered as attenuated live microbes, inactivated pathogens, purified proteins or virus-like particles. Newer generation vaccines are based on the delivery of genes encoding for a protein antigen that can be transcribed and translated by host cells. Despite current challenges to improve delivery and immunogenicity, DNA vaccination has several major advantages over traditional vaccines or over other types of investigational vaccine platforms. DNA vaccines do not integrate into the host genome, they are stable, can be manufactured with relative ease and efficiency, have been safe in clinical trials and do not require a preservative in final preparation. The lack of vector-specific immunity allows the potential for DNA vaccines to be used as a platform technology for emerging viral diseases by allowing the simple exchange of genes encoding vaccine antigens in a stable plasmid backbone.

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    ABSTRACT: DNA vaccination with plasmid has conventionally involved vectors designed for transient expression of antigens in injected tissues. Next generation plasmids are being developed for site-directed integration of transgenes into safe sites in host genomes and may provide an innovative approach for stable and sustained expression of antigens for vaccination. The goal of this study was to evaluate in vivo antigen expression and the generation of cell mediated immunity in mice injected with a non-integrating plasmid compared to a plasmid with integrating potential. Hyperactive piggyBac transposase-based integrating vectors (pmhyGENIE-3) contained a transgene encoding either eGFP (pmhyGENIE-3-eGFP) or luciferase (pmhyGENIE-3-GL3), and were compared to transposase-deficient plasmids with the same transgene and DNA backbone. Both non-integrating and integrating plasmids were equivalent at day 1 for protein expression at the site of injection. While protein expression from the non-integrating plasmid was lost by day 14, the pmhyGENIE-3 was found to exhibit sustained protein expression up to 28 days post-injection. Vaccination with pmhyGENIE-3-eGFP resulted in a robust CD8(+) T cell response that was three-fold higher than that of non-integrating plasmid vaccinations. Additionally we observed in splenocyte restimulation experiments that only the vaccination with pmhyGENIE-3-eGFP was characterized by IFNγ producing CD8(+) T cells. Overall, these findings suggest that plasmids designed to direct integration of transgenes into the host genome are a promising approach for designing DNA vaccines. Robust cell mediated CD8(+) T cell responses generated using integrating plasmids may provide effective, sustained protection against intracellular pathogens or tumor antigens.
    Vaccine 02/2014; 32(15). DOI:10.1016/j.vaccine.2014.01.063 · 3.49 Impact Factor
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    ABSTRACT: The development of an effective HIV vaccine is still a major scientific challenge. HIV vaccine trials conducted until now were not able to induce broad neutralizing antibodies or effective cell mediated immune responses. More recently, CD4+ T cells have been shown to play an important role in viral control and better disease prognosis. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4+ T cell responses in BALB/c and in multiple HLA class II transgenic mice. Despite the advantages of DNA vaccines and a large number of clinical trials, it has been a challenge to transfer the success of inducing potent immunity observed in animal models to humans. Here, we sought to evaluate the potential use of bupivacaine, a local anesthetic, as an adjuvant for HIVBr18. We observed that the concomitant administration of the local anesthetic bupivacaine with the DNA vaccine HIVBr18 increased the magnitude of CD4+ and CD8+ T cell responses and cytokine production without compromising their breadth. Furthermore, we demonstrate that coadministration of bupivacaine also impacted the longevity of specific immune responses. Since bupivacaine is used in clinical settings, we believe that this concept may contribute to overcome the limited immunogenicity of DNA vaccines in humans.
    01/2014; 3:95–101. DOI:10.1016/j.trivac.2014.05.001
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    ABSTRACT: The development of a vaccine would be essential for the control of schistosomiasis, which is recognized as the most important human helminth infection in terms of morbidity and mortality. A new approach of oral vaccination with DNA-chitosan nanoparticles appears interesting because of their great stability and the ease of target accessibility, besides chitosan immunostimulatory properties. Here we described that chitosan nanoparticles loaded with plasmid DNA encoding Rho1-GTPase protein of Schistosoma mansoni, prepared at different molar ratios of primary amines to DNA phosphate anion (N/P), were able to complex electrostatically with DNA and condense it into positively charged nanostructures. Nanoparticles were able to maintain zeta potential and size characteristics in media that simulate gastric (SGF) and intestinal fluids (SIF). Further in vivo studies showed that oral immunization was not able to induce high levels of specific antibodies but induced high levels of the modulatory cytokine IL-10. This resulted in a significative reduce of liver pathology, although it could not protect mice of infection challenge with S. mansoni worms. Mice immunized only with chitosan nanoparticles presented 47% of protection against parasite infection, suggesting an important role of chitosan in inducing a protective immune response against schistosomiasis, which will be more explored in further studies.
    The Scientific World Journal 04/2012; 2012:938457. DOI:10.1100/2012/938457 · 1.73 Impact Factor


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