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1

Omaji, G. O., T. M. Anakaa, and L. E. Ilouno. "DNA VACCINES: CHALLENGES AND APPROACHES." FUDMA JOURNAL OF SCIENCES 5, no. 4 (January 28, 2022): 216–21. http://dx.doi.org/10.33003/fjs-2021-0504-808.

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Since the discovery of the first vaccine about 200 years ago, improvement in vaccine development approaches has occurred over the years. Most notably, the emergence of DNA vaccines. DNA vaccines can evoke both humoral and cell mediated immunity, they are safe and have several advantages over other vaccines types. Despite this, poor immunogenicity produced by DNA vaccines in humans has called for novel strategies. This review highlight ways to improve the efficacy of DNA vaccines through plasmid modification, delivery systems, prime boost and addition of adjuvants. The review also discusses the potential of DNA vaccine in pandemic settings such as that of corona virus disease 2019 (COVID-19)
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2

Tuchkov, I. V., and A. K. Nikiforov. "Antirabies DNA Immunization." Problems of Particularly Dangerous Infections, no. 2(104) (April 20, 2010): 74–77. http://dx.doi.org/10.21055/0370-1069-2010-2(104)-74-77.

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Cited are literary data related to the development of DNA vaccines against rabies virus. Research results regarding gene vaccination of different models of laboratory animals and different ways of vaccine introduction are presented. Possibility to potentiate immunogenicity of DNA vaccines using adjuvants and cytokines is considered. Ways of improving of polynucleotide vaccines are discussed.
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3

&NA;. "DNA Vaccines—“Designer Vaccines”?" Infectious Diseases in Clinical Practice 9, no. 2 (February 2000): 41–42. http://dx.doi.org/10.1097/00019048-200009020-00003.

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4

Pushko, Peter, Igor S. Lukashevich, Dylan M. Johnson, and Irina Tretyakova. "Single-Dose Immunogenic DNA Vaccines Coding for Live-Attenuated Alpha- and Flaviviruses." Viruses 16, no. 3 (March 10, 2024): 428. http://dx.doi.org/10.3390/v16030428.

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Single-dose, immunogenic DNA (iDNA) vaccines coding for whole live-attenuated viruses are reviewed. This platform, sometimes called immunization DNA, has been used for vaccine development for flavi- and alphaviruses. An iDNA vaccine uses plasmid DNA to launch live-attenuated virus vaccines in vitro or in vivo. When iDNA is injected into mammalian cells in vitro or in vivo, the RNA genome of an attenuated virus is transcribed, which starts replication of a defined, live-attenuated vaccine virus in cell culture or the cells of a vaccine recipient. In the latter case, an immune response to the live virus vaccine is elicited, which protects against the pathogenic virus. Unlike other nucleic acid vaccines, such as mRNA and standard DNA vaccines, iDNA vaccines elicit protection with a single dose, thus providing major improvement to epidemic preparedness. Still, iDNA vaccines retain the advantages of other nucleic acid vaccines. In summary, the iDNA platform combines the advantages of reverse genetics and DNA immunization with the high immunogenicity of live-attenuated vaccines, resulting in enhanced safety and immunogenicity. This vaccine platform has expanded the field of genetic DNA and RNA vaccines with a novel type of immunogenic DNA vaccines that encode entire live-attenuated viruses.
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Srivastava, Indresh K., and Manmohan Singh. "DNA Vaccines." International Journal of Pharmaceutical Medicine 19, no. 1 (2005): 15–28. http://dx.doi.org/10.2165/00124363-200519010-00004.

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6

Lai, Wayne C., and Michael Bennett. "DNA Vaccines." Critical Reviews™ in Immunology 18, no. 5 (1998): 449–84. http://dx.doi.org/10.1615/critrevimmunol.v18.i5.30.

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7

Sung, Seung Yong. "DNA Vaccines." Journal of the Korean Medical Association 40, no. 1 (1997): 132. http://dx.doi.org/10.5124/jkma.1997.40.1.132.

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8

Reyes-Sandoval, Arturo, and Hildegund Ertl. "DNA Vaccines." Current Molecular Medicine 1, no. 2 (May 1, 2001): 217–43. http://dx.doi.org/10.2174/1566524013363898.

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9

Subramaniam, Geetha. "DNA Vaccines." Journal of Health and Translational Medicine 3, no. 1 (December 28, 1998): 18–21. http://dx.doi.org/10.22452/jummec.vol3no1.4.

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10

Spiegelberg, H. L., and E. Raz. "DNA vaccines." Allergy 54, s56 (October 1999): 47–48. http://dx.doi.org/10.1111/j.1398-9995.1999.tb04443.x.

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11

McDonnell, W. Michael, and Frederick K. Askari. "DNA Vaccines." New England Journal of Medicine 334, no. 1 (January 4, 1996): 42–45. http://dx.doi.org/10.1056/nejm199601043340110.

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12

ROBINSON, HARRIET L., SHAN LU, DAVID M. FELTQUATE, CELIA T. TORRES, JOAN RICHMOND, CHRISTINE M. BOYLE, MERRIBETH J. MORIN, et al. "DNA Vaccines." AIDS Research and Human Retroviruses 12, no. 5 (March 20, 1996): 455–57. http://dx.doi.org/10.1089/aid.1996.12.455.

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13

Koide, Yukio, Toshi Nagata, Atsushi Yoshida, and Masato Uchijima. "DNA Vaccines." Japanese Journal of Pharmacology 83, no. 3 (2000): 167–74. http://dx.doi.org/10.1016/s0021-5198(19)30581-5.

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14

Donnelly, John J., Jeffrey B. Ulmer, and Margaret A. Liu. "DNA vaccines." Life Sciences 60, no. 3 (December 1996): 163–72. http://dx.doi.org/10.1016/s0024-3205(96)00502-4.

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15

Encke, Jens, Jasper zu Putlitz, and Jack R. Wands. "DNA Vaccines." Intervirology 42, no. 2-3 (1999): 117–24. http://dx.doi.org/10.1159/000024971.

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16

Webster, Robert G., and Harriet L. Robinson. "DNA Vaccines." BioDrugs 8, no. 4 (October 1997): 273–92. http://dx.doi.org/10.2165/00063030-199708040-00004.

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17

Felgner, Philip L. "DNA vaccines." Current Biology 8, no. 16 (July 1998): R551—R553. http://dx.doi.org/10.1016/s0960-9822(07)00358-2.

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18

Montgomery, Donna L., Jeffrey B. Ulmer, John J. Donnelly, and Margaret A. Liu. "DNA Vaccines." Pharmacology & Therapeutics 74, no. 2 (January 1997): 195–205. http://dx.doi.org/10.1016/s0163-7258(97)82003-7.

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19

Ulmer, Jeffrey B., Jerald C. Sadoff, and Margaret A. Liu. "DNA vaccines." Current Opinion in Immunology 8, no. 4 (August 1996): 531–36. http://dx.doi.org/10.1016/s0952-7915(96)80042-2.

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20

Robinson, Harriet L. "DNA vaccines." Clinical Microbiology Newsletter 22, no. 3 (February 2000): 17–22. http://dx.doi.org/10.1016/s0196-4399(00)87959-3.

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21

Gregersen, Jens-Peter. "DNA vaccines." Naturwissenschaften 88, no. 12 (October 10, 2001): 504–13. http://dx.doi.org/10.1007/s00114-001-0270-2.

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22

Donnelly, John J., Jeffrey B. Ulmer, John W. Shiver, and Margaret A. Liu. "DNA VACCINES." Annual Review of Immunology 15, no. 1 (April 1997): 617–48. http://dx.doi.org/10.1146/annurev.immunol.15.1.617.

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23

Coban, Cevayir, Kouji Kobiyama, Nao Jounai, Miyuki Tozuka, and Ken J. Ishii. "DNA vaccines." Human Vaccines & Immunotherapeutics 9, no. 10 (October 4, 2013): 2216–21. http://dx.doi.org/10.4161/hv.25893.

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24

Koide, Yukio, Toshi Nagata, Atsushi Yoshida, and Masato Uchijima. "DNA Vaccines." Japanese Journal of Pharmacology 83, no. 3 (2000): 167–74. http://dx.doi.org/10.1254/jjp.83.167.

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25

Scott-Taylor, Tim H., and Angus G. Dalgleish. "DNA vaccines." Expert Opinion on Investigational Drugs 9, no. 3 (March 2000): 471–80. http://dx.doi.org/10.1517/13543784.9.3.471.

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26

Robinson, Harriet L., and Celia A. T. Torres. "DNA vaccines." Seminars in Immunology 9, no. 5 (October 1997): 271–83. http://dx.doi.org/10.1006/smim.1997.0083.

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27

Rangarajan, P. N. "DNA vaccines." Resonance 7, no. 7 (July 2002): 25–34. http://dx.doi.org/10.1007/bf02836750.

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28

Ulmer, Jeffrey B. "DNA vaccines." Journal of Infection 40, no. 2 (March 2000): A7. http://dx.doi.org/10.1016/s0163-4453(00)80029-8.

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29

Fioretti, Daniela, Sandra Iurescia, Vito Michele Fazio, and Monica Rinaldi. "DNA Vaccines: Developing New Strategies against Cancer." Journal of Biomedicine and Biotechnology 2010 (2010): 1–16. http://dx.doi.org/10.1155/2010/174378.

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Due to their rapid and widespread development, DNA vaccines have entered into a variety of human clinical trials for vaccines against various diseases including cancer. Evidence that DNA vaccines are well tolerated and have an excellent safety profile proved to be of advantage as many clinical trials combines the first phase with the second, saving both time and money. It is clear from the results obtained in clinical trials that such DNA vaccines require much improvement in antigen expression and delivery methods to make them sufficiently effective in the clinic. Similarly, it is clear that additional strategies are required to activate effective immunity against poorly immunogenic tumor antigens. Engineering vaccine design for manipulating antigen presentation and processing pathways is one of the most important aspects that can be easily handled in the DNA vaccine technology. Several approaches have been investigated including DNA vaccine engineering, co-delivery of immunomodulatory molecules, safe routes of administration, prime-boost regimen and strategies to break the immunosuppressive networks mechanisms adopted by malignant cells to prevent immune cell function. Combined or single strategies to enhance the efficacy and immunogenicity of DNA vaccines are applied in completed and ongoing clinical trials, where the safety and tolerability of the DNA platform are substantiated. In this review on DNA vaccines, salient aspects on this topic going from basic research to the clinic are evaluated. Some representative DNA cancer vaccine studies are also discussed.
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30

Bergen, Jeroen Van, Tsolere Arakelian, Kedar Moharana, Bram Teunisse, Iris Zoutendijk, Marcel Camps, Ramon Arens, Ferry Ossendorp, and Gerben Zondag. "770 Personalized synthetic polyepitope DNA cancer vaccines encoding a novel pyroptotic adjuvant to generate effective anti-tumor T cell immunity." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (November 2021): A805. http://dx.doi.org/10.1136/jitc-2021-sitc2021.770.

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BackgroundAs every tumor carries its unique set of neoantigens distinguishing it from healthy tissue, cancer vaccines need to be produced quickly and on an individual basis to swiftly induce a broad immune response targeting multiple antigens. DNA provides an ideal platform to achieve this, as a single polyepitope vaccine can encode multiple (>20) antigens. However, standard plasmid DNA vaccines take months to produce and tend to be poorly immunogenic in humans.MethodsTo address the first issue, a GMP-compatible method (AmpliVax) was developed that allows the simultaneous production of milligram amounts of multiple DNA vaccines in single vessel reactions within two days. This method relies on a primer-free, isothermal, rolling-circle amplification using high fidelity DNA polymerase and RNA polymerase to amplify circular DNA templates into linear double-stranded concatemers. Concatemers are digested into single linear expression cassettes which are subsequently protected by nuclease-resistant caps. To improve DNA vaccine immunogenicity, two avenues were explored. First, neoantigen DNA vaccines were tested in a therapeutic setting together with a checkpoint inhibitor drug. Second, DNA vaccines were combined with a novel caspase-1-based genetic adjuvant (PyroVant) that induces pyroptosis by exploiting the inflammasome pathway.ResultsUpon intradermal injection in mice, synthetic AmpliVax DNA vaccines matched plasmid DNA vaccines in terms of in vivo expression, immunogenicity and tumor protection. While treatment of mice carrying an MC38 colorectal tumor with either a polyepitope neoantigen DNA vaccine or anti-PD-1 did not significantly delay tumor outgrowth compared to untreated mice (0% survival), the combination of the neoantigen vaccine and anti-PD1 resulted in up to 70% tumor-free survival. PyroVant DNA accelerated and amplified antigen-specific CD8 T cell responses when administered simultaneously with a polyepitope DNA vaccine. What's more, subsequent challenge with melanoma cells revealed that PyroVant also significantly improved tumor-free survival.ConclusionsIn conclusion, we have created a novel synthetic DNA vaccine platform suitable for the production of effective personalized cancer vaccines. Current efforts are aimed at testing combinations of therapeutic synthetic DNA vaccines, PyroVant and checkpoint inhibitors in multiple pre-clinical tumor models.
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31

Kozak, Michael, and Jiafen Hu. "DNA Vaccines: Their Formulations, Engineering and Delivery." Vaccines 12, no. 1 (January 11, 2024): 71. http://dx.doi.org/10.3390/vaccines12010071.

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The concept of DNA vaccination was introduced in the early 1990s. Since then, advancements in the augmentation of the immunogenicity of DNA vaccines have brought this technology to the market, especially in veterinary medicine, to prevent many diseases. Along with the successful COVID mRNA vaccines, the first DNA vaccine for human use, the Indian ZyCovD vaccine against SARS-CoV-2, was approved in 2021. In the current review, we first give an overview of the DNA vaccine focusing on the science, including adjuvants and delivery methods. We then cover some of the emerging science in the field of DNA vaccines, notably efforts to optimize delivery systems, better engineer delivery apparatuses, identify optimal delivery sites, personalize cancer immunotherapy through DNA vaccination, enhance adjuvant science through gene adjuvants, enhance off-target and heritable immunity through epigenetic modification, and predict epitopes with bioinformatic approaches. We also discuss the major limitations of DNA vaccines and we aim to address many theoretical concerns.
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32

Liu. "A Comparison of Plasmid DNA and mRNA as Vaccine Technologies." Vaccines 7, no. 2 (April 24, 2019): 37. http://dx.doi.org/10.3390/vaccines7020037.

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This review provides a comparison of the theoretical issues and experimental findings for plasmid DNA and mRNA vaccine technologies. While both have been under development since the 1990s, in recent years, significant excitement has turned to mRNA despite the licensure of several veterinary DNA vaccines. Both have required efforts to increase their potency either via manipulating the plasmid DNA and the mRNA directly or through the addition of adjuvants or immunomodulators as well as delivery systems and formulations. The greater inherent inflammatory nature of the mRNA vaccines is discussed for both its potential immunological utility for vaccines and for the potential toxicity. The status of the clinical trials of mRNA vaccines is described along with a comparison to DNA vaccines, specifically the immunogenicity of both licensed veterinary DNA vaccines and select DNA vaccine candidates in human clinical trials.
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Jin, Yanwen, Cheng Cao, Ping Li, Xuan Liu, Wei Huang, Chufang Li, and Qingjun Ma. "Boosting Immune Response to Hepatitis B DNA Vaccine by Coadministration of Prothymosin α-Expressing Plasmid." Clinical Diagnostic Laboratory Immunology 12, no. 12 (December 2005): 1364–69. http://dx.doi.org/10.1128/cdli.12.12.1364-1369.2005.

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ABSTRACT DNA vaccines induce protective humoral and cell-mediated immune responses in several animal models. However, compared to conventional vaccines, DNA vaccines usually induce poor antibody responses. In this study, we report that coadministration of a hepatitis B virus (HBV) DNA vaccine with prothymosin α as an adjuvant improves antibody responses to HBV S antigen. We also observed higher seroconversion rates and higher antibody titers. Prothymosin α appears to increase the number and affinity of hepatitis B surface antigen-specific, gamma interferon-secreting T cells and to enhance cellular immune response to the PreS2S DNA vaccine. Interestingly, administering the DNA separately from the prothymosin α plasmid abrogated the enhancement of DNA vaccine potency. The results suggest that prothymosin α may be a promising adjuvant for DNA vaccines.
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Dai, Yang, Yinchang Zhu, Donald A. Harn, Xiaoting Wang, Jianxia Tang, Song Zhao, Fei Lu, and Xiaohong Guan. "DNA Vaccination by Electroporation and Boosting with Recombinant Proteins Enhances the Efficacy of DNA Vaccines for Schistosomiasis Japonica." Clinical and Vaccine Immunology 16, no. 12 (October 7, 2009): 1796–803. http://dx.doi.org/10.1128/cvi.00231-09.

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ABSTRACT Schistosomiasis japonica is an endemic, zoonotic disease of major public health importance in China. Control programs combining chemotherapy and snail killing have not been able to block transmission of infection in lakes and marsh regions. Vaccination is needed as a complementary approach to the ongoing control programs. In the present study, we wanted to determine if the efficacies of DNA vaccines encoding the 23-kDa tetraspanin membrane protein (SjC23), triose phosphate isomerase (SjCTPI), and sixfold-repeated genes of the complementarity determining region 3 (CDR3) in the H chain of NP30 could be enhanced by boosting via electroporation in vivo and/or with cocktail protein vaccines. Mice vaccinated with cocktail DNA vaccines showed a significant worm reduction of 32.88% (P < 0.01) and egg reduction of 36.20% (P < 0.01). Vaccine efficacy was enhanced when animals were boosted with cocktail protein vaccines; adult worm and liver egg burdens were reduced 45.35% and 48.54%, respectively. Nearly identical results were obtained in mice boosted by electroporation in vivo, with adult worm and egg burdens reduced by 45.00% and 50.88%, respectively. The addition of a protein vaccine boost to this regimen further elevated efficacy to approximately 60% for adult worm burden and greater than 60% for liver egg reduction. The levels of interleukin-2, gamma interferon, and the ratios of immunoglobulin G2a (IgG2a)/IgG1 clearly showed that cocktail DNA vaccines induced CD4+ Th1-type responses. Boosting via either electroporation or with recombinant proteins significantly increased associated immune responses over those seen in mice vaccinated solely with DNA vaccines. Thus, schistosome DNA vaccine efficacy was significantly enhanced via boosting by electroporation in vivo and/or cocktail protein vaccines.
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Kisakova, Lyubov A., Evgeny K. Apartsin, Lily F. Nizolenko, and Larisa I. Karpenko. "Dendrimer-Mediated Delivery of DNA and RNA Vaccines." Pharmaceutics 15, no. 4 (March 30, 2023): 1106. http://dx.doi.org/10.3390/pharmaceutics15041106.

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DNA and RNA vaccines (nucleic acid-based vaccines) are a promising platform for vaccine development. The first mRNA vaccines (Moderna and Pfizer/BioNTech) were approved in 2020, and a DNA vaccine (Zydus Cadila, India), in 2021. They display unique benefits in the current COVID-19 pandemic. Nucleic acid-based vaccines have a number of advantages, such as safety, efficacy, and low cost. They are potentially faster to develop, cheaper to produce, and easier to store and transport. A crucial step in the technology of DNA or RNA vaccines is choosing an efficient delivery method. Nucleic acid delivery using liposomes is the most popular approach today, but this method has certain disadvantages. Therefore, studies are actively underway to develop various alternative delivery methods, among which synthetic cationic polymers such as dendrimers are very attractive. Dendrimers are three-dimensional nanostructures with a high degree of molecular homogeneity, adjustable size, multivalence, high surface functionality, and high aqueous solubility. The biosafety of some dendrimers has been evaluated in several clinical trials presented in this review. Due to these important and attractive properties, dendrimers are already being used to deliver a number of drugs and are being explored as promising carriers for nucleic acid-based vaccines. This review summarizes the literature data on the development of dendrimer-based delivery systems for DNA and mRNA vaccines.
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Lim, Michael, Abu Zayed Md Badruddoza, Jannatul Firdous, Mohammad Azad, Adnan Mannan, Taslim Ahmed Al-Hilal, Chong-Su Cho, and Mohammad Ariful Islam. "Engineered Nanodelivery Systems to Improve DNA Vaccine Technologies." Pharmaceutics 12, no. 1 (January 1, 2020): 30. http://dx.doi.org/10.3390/pharmaceutics12010030.

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DNA vaccines offer a flexible and versatile platform to treat innumerable diseases due to the ease of manipulating vaccine targets simply by altering the gene sequences encoded in the plasmid DNA delivered. The DNA vaccines elicit potent humoral and cell-mediated responses and provide a promising method for treating rapidly mutating and evasive diseases such as cancer and human immunodeficiency viruses. Although this vaccine technology has been available for decades, there is no DNA vaccine that has been used in bed-side application to date. The main challenge that hinders the progress of DNA vaccines and limits their clinical application is the delivery hurdles to targeted immune cells, which obstructs the stimulation of robust antigen-specific immune responses in humans. In this updated review, we discuss various nanodelivery systems that improve DNA vaccine technologies to enhance the immunological response against target diseases. We also provide possible perspectives on how we can bring this exciting vaccine technology to bedside applications.
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Chapman, Rosamund, Michiel van Diepen, Nicola Douglass, Tandile Hermanus, Penny L. Moore, and Anna-Lise Williamson. "Needle-Free Devices and CpG-Adjuvanted DNA Improve Anti-HIV Antibody Responses of Both DNA and Modified Vaccinia Ankara-Vectored Candidate Vaccines." Vaccines 11, no. 2 (February 7, 2023): 376. http://dx.doi.org/10.3390/vaccines11020376.

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The combination of mosaic Gag and CAP256 envelope in an HIV vaccine regimen comprising DNA prime and modified vaccinia Ankara (MVA) boost followed by protein boost has previously been shown to generate robust autologous Tier 2 neutralizing antibodies (nAbs) in rabbits. Further refinements of this strategy have been investigated to improve antibody responses. The delivery of both DNA and recombinant MVA vaccines with a needle-free device was compared to delivery by injection, and the effect of formulating the DNA vaccine with adjuvant CpG ODN 1826 was determined. The Pharmajet Stratis® needle-free injection device (PharmaJet, Golden, CO, USA) improved binding antibody responses to the DNA vaccine as well as both binding and neutralizing antibody responses to the MVA vaccines. Formulation of the DNA vaccines with CpG adjuvant further improved the antibody responses. A shortened vaccination regimen of a single DNA inoculation followed by a single MVA inoculation did not elicit Tier 1B nor Tier 2 neutralization responses as produced by the two DNA, followed by two MVA vaccination regimen. This study showed the immunogenicity of HIV DNA and MVA vaccines administered in a DDMM regimen could be improved using the PharmaJet Stratis needle-free injection device and formulation of the DNA vaccines with CpG adjuvant.
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Saadh, Mohamed Jamal, Hala Mousa Sbaih, Ali Mohammed Mustafa, Abeer Mohammad Kharshid, and Mohd Alaraj. "Vaccines: Purified Macromolecules as Vaccines and DNA Vaccines." Indian Journal of Public Health Research & Development 10, no. 11 (2019): 2424. http://dx.doi.org/10.5958/0976-5506.2019.03970.6.

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Wu, Pinyi, Haitao Jiang, Hao-chun Shen, and Mi-Hua Tao. "Immunogenicity comparison of neoantigen vaccines through different delivery platform." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 169.27. http://dx.doi.org/10.4049/jimmunol.204.supp.169.27.

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Abstract Neoantigens are promising cancer vaccine candidates because they’re cancer-specific and can be predicted from the patient’s genomic data. A major challenge for developing potent neoantigen vaccines is the low immunogenicity of neoepitopes. DNA vaccines can deliver multiple epitopes and cytokines as an adjuvant in a single plasmid, and its immunogenicity can be further enhanced through heterologous prime-boost strategy. Here, we hypothesized utilizing DNA prime, adenovirus boost (refer to the DDA approach) strategy can improve the immunogenicity of neoantigen vaccines. To investigate whether vaccination through the DDA approach or DDA combine GM-CSF as adjuvant can improve the immunogenicity of neoantigen vaccines. Using IEDB analysis resource to predict and rank the top 21 MHC class I epitopes (short peptide) for the B16F10 tumor while 27mer peptides (long peptide) were synthesized to cover both MHC class I and class II epitopes. The 27mer neoantigen sequences of the selected 21 MHC class I epitopes were cloned into one plasmid and adenoviral vector with or without GM-CSF sequence linked by p2a. Mice were immunized through the DDA approach or peptides with polyI:C. In the peptide vaccine, the majority of the response were mediated by CD4+ T cells, only one peptide can induce CD8+ T cells response. For the DDA approach, 14% epitopes can induce CD8+ T cell response in mice immunized with DNA vaccine. Moreover, in the group with genetic encoded GM-CSF. it has significantly enhanced CD8+T cell response compare to the former, which dramatically improved the immunogenicity of neoantigen vaccines. Our preliminary data also showed that immunization of DNA vaccines significantly delayed tumor growth.
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Dupuy, Lesley C., Michelle J. Richards, Brian D. Livingston, Drew Hannaman, and Connie S. Schmaljohn. "A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges." Journal of Immunology Research 2018 (June 3, 2018): 1–15. http://dx.doi.org/10.1155/2018/8521060.

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There remains a need for vaccines that can safely and effectively protect against the biological threat agents Venezuelan (VEEV), western (WEEV), and eastern (EEEV) equine encephalitis virus. Previously, we demonstrated that a VEEV DNA vaccine that was optimized for increased antigen expression and delivered by intramuscular (IM) electroporation (EP) elicited robust and durable virus-specific antibody responses in multiple animal species and provided complete protection against VEEV aerosol challenge in mice and nonhuman primates. Here, we performed a comparative evaluation of the immunogenicity and protective efficacy of individual optimized VEEV, WEEV, and EEEV DNA vaccines with that of a 1 : 1 : 1 mixture of these vaccines, which we have termed the 3-EEV DNA vaccine, when delivered by IM EP. The individual DNA vaccines and the 3-EEV DNA vaccine elicited robust and durable virus-specific antibody responses in mice and rabbits and completely protected mice from homologous VEEV, WEEV, and EEEV aerosol challenges. Taken together, the results from these studies demonstrate that the individual VEEV, WEEV, and EEEV DNA vaccines and the 3-EEV DNA vaccine delivered by IM EP provide an effective means of eliciting protection against lethal encephalitic alphavirus infections in a murine model and represent viable next-generation vaccine candidates that warrant further development.
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Shafaati, Maryam, Massoud Saidijam, Meysam Soleimani, Fereshte Hazrati, Rasoul Mirzaei, Bagher Amirheidari, Hamid Tanzadehpanah, et al. "A brief review on DNA vaccines in the era of COVID-19." Future Virology 17, no. 1 (January 2022): 49–66. http://dx.doi.org/10.2217/fvl-2021-0170.

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This article provides a brief overview of DNA vaccines. First, the basic DNA vaccine design strategies are described, then specific issues related to the industrial production of DNA vaccines are discussed, including the production and purification of DNA products such as plasmid DNA, minicircle DNA, minimalistic, immunologically defined gene expression (MIDGE) and Doggybone™. The use of adjuvants to enhance the immunogenicity of DNA vaccines is then discussed. In addition, different delivery routes and several physical and chemical methods to increase the efficacy of DNA delivery into cells are explained. Recent preclinical and clinical trials of DNA vaccines for COVID-19 are then summarized. Lastly, the advantages and obstacles of DNA vaccines are discussed.
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42

Ledesma-Feliciano, Carmen, Ros Chapman, Jay W. Hooper, Kira Elma, Darin Zehrung, Miles B. Brennan, and Erin K. Spiegel. "Improved DNA Vaccine Delivery with Needle-Free Injection Systems." Vaccines 11, no. 2 (January 28, 2023): 280. http://dx.doi.org/10.3390/vaccines11020280.

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DNA vaccines have inherent advantages compared to other vaccine types, including safety, rapid design and construction, ease and speed to manufacture, and thermostability. However, a major drawback of candidate DNA vaccines delivered by needle and syringe is the poor immunogenicity associated with inefficient cellular uptake of the DNA. This uptake is essential because the target vaccine antigen is produced within cells and then presented to the immune system. Multiple techniques have been employed to boost the immunogenicity and protective efficacy of DNA vaccines, including physical delivery methods, molecular and traditional adjuvants, and genetic sequence enhancements. Needle-free injection systems (NFIS) are an attractive alternative due to the induction of potent immunogenicity, enhanced protective efficacy, and elimination of needles. These advantages led to a milestone achievement in the field with the approval for Restricted Use in Emergency Situation of a DNA vaccine against COVID-19, delivered exclusively with NFIS. In this review, we discuss physical delivery methods for DNA vaccines with an emphasis on commercially available NFIS and their resulting safety, immunogenic effectiveness, and protective efficacy. As is discussed, prophylactic DNA vaccines delivered by NFIS tend to induce non-inferior immunogenicity to electroporation and enhanced responses compared to needle and syringe.
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43

&NA;. "DNA fusion vaccines." Inpharma Weekly &NA;, no. 1166 (December 1998): 10. http://dx.doi.org/10.2165/00128413-199811660-00016.

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44

Popov, Yu A., and N. I. Mikshis. "Genetic (DNA) Vaccines." Problems of Particularly Dangerous Infections, no. 3(105) (June 20, 2010): 20–24. http://dx.doi.org/10.21055/0370-1069-2010-3(105)-20-24.

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With the development of various branches of medicine and biology the classical ideas about means to prevent infectious diseases have changed. Nowadays in different countries of the world, investigations are carried out intensively in the sphere of genetic vaccines. Distinctive feature of DNA-vaccination is long lasted expression in eukaryotic cell cytoplasm of nucleic acids encoding synthesis of immunogenic proteins. Genetic vaccines induce both humoral and cellular responses accompanied by production of large pool of immunological memory cells. A number of questions regarding features of gene-engineered construction and transfer of DNA-vaccines into the cells of macroorganism, structure of DNA-vaccines and mechanisms of immune response generation are considered in the review. Attention is paid on the safety of gene vaccination and ways to improve its efficiency.
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Abdelnoor, A. M. "Plasmid DNA Vaccines." Current Drug Targets - Immune, Endocrine & Metabolic Disorders 1, no. 1 (May 1, 2001): 79–92. http://dx.doi.org/10.2174/1568008013341776.

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46

Ulmer, Jeffrey B. "Tuberculosis DNA Vaccines." Scandinavian Journal of Infectious Diseases 33, no. 4 (January 2001): 246–48. http://dx.doi.org/10.1080/003655401300077162.

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Ulmer, Jeffrey B. "Tuberculosis DNA Vaccines." Scandinavian Journal of Infectious Diseases 33, no. 1 (January 2001): 74–76. http://dx.doi.org/10.1080/003655401753382611.

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48

CHANG, GWONG-JEN J., BRENT S. DAVIS, ANN R. HUNT, DEREK A. HOLMES, and GORO KUNO. "Flavivirus DNA Vaccines." Annals of the New York Academy of Sciences 951, no. 1 (January 25, 2006): 272–85. http://dx.doi.org/10.1111/j.1749-6632.2001.tb02703.x.

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49

Ulmer, Jeffrey B. "Influenza DNA vaccines." Vaccine 20 (May 2002): S74—S76. http://dx.doi.org/10.1016/s0264-410x(02)00136-6.

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50

Wu, T.-C. "HPV DNA vaccines." Frontiers in Bioscience 8, no. 4 (2003): d55–68. http://dx.doi.org/10.2741/936.

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