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DNA is a rapidly developing vaccine platform for cancer and infectious and non-infectious diseases. Plasmids are used as immunogens to encode proteins to be further synthesized in vaccine recipients. DNA is mainly synthetic, ensuring enhanced expression in the cells of vaccine recipients (mostly mammalians). Their introduction into the host induces antibody and cellular responses. The latter are often more pronounced, and mimic the events occurring in infection, especially viral. There are a few distinct ways in which the vaccine antigen can be processed and presented, which determine the resulting immune response and which can be manipulated. Routinely, the antigen synthesized within the host cell is processed by proteasome, loaded onto, and presented in a complex with MHC I molecules. Processing can be re-routed to the lysosome, or immunogen can be secreted for further presentation in a complex with MHC II. Apart from expression, vaccination efficacy depends on DNA delivery. DNA immunogens are generally administered by intramuscular or intradermal injections, usually followed by electroporation, which enhances delivery 1000-fold. Other techniques are also used, such as noninvasive introduction by biojectors, skin applications with plasters and microneedles/chips, sonication, magnetofection, and even tattooing. An intense debate regarding the pros and cons of different routes of delivery is ongoing. A number of studies have compared the effect of delivery methods at the level of immunogen expression, and the magnitude and specificity of the resulting immune response. According to some, the delivery route determines immunogenic performance; according to others, it can modulate the level of response, but not its specificity or polarity. The progress of research aiming at the optimization of DNA vaccine design, delivery, and immunogenic performance has led to a marked increase in their efficacy in large species and humans. New DNA vaccines for use in the treatment of infectious diseases, cancer, allergies, and autoimmunity are forthcoming. This Special Issue covers various aspects of DNA vaccine development.

Medicine --- Epidemiology & medical statistics --- alphaviruses --- layered RNA/DNA vectors --- DNA vaccines --- RNA replicons --- recombinant particles --- tumor regression --- protection against tumor challenges and infectious agents --- ebola virus disease --- artificial T-cell antigens --- DNA vaccine constructs --- computer design --- gene expression --- immunogenicity --- DNA vaccine --- mRNA vaccine --- plasmid DNA --- in vitro transcribed mRNA --- immune responses --- formulations --- Cytolytic T Lymphocytes --- antibodies --- innate immunity --- adjuvants --- vaccine delivery --- plasmid --- cytolytic --- perforin --- bicistronic --- HCV --- HIV --- IL-36 --- adjuvant --- DNA --- Zika --- Epstein-Barr virus --- latent proteins --- LMP2 --- EBNA1 --- LMP1 --- HIV-1 --- enhancer element --- circovirus --- influenza --- immunization --- intranasal --- lipid --- flagellin --- BCG --- vaccine --- rBCG --- HTI --- T-cell --- AIDS --- clinical trial --- therapeutic vaccine --- hepatitis C virus (HCV) --- mesenchymal stem cells (MSC) --- modified MSC --- DNA immunization --- nonstructural HCV proteins --- immune response --- HCV vaccine --- myeloid derived suppressor cells (MDSCs) --- n/a

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DNA is a rapidly developing vaccine platform for cancer and infectious and non-infectious diseases. Plasmids are used as immunogens to encode proteins to be further synthesized in vaccine recipients. DNA is mainly synthetic, ensuring enhanced expression in the cells of vaccine recipients (mostly mammalians). Their introduction into the host induces antibody and cellular responses. The latter are often more pronounced, and mimic the events occurring in infection, especially viral. There are a few distinct ways in which the vaccine antigen can be processed and presented, which determine the resulting immune response and which can be manipulated. Routinely, the antigen synthesized within the host cell is processed by proteasome, loaded onto, and presented in a complex with MHC I molecules. Processing can be re-routed to the lysosome, or immunogen can be secreted for further presentation in a complex with MHC II. Apart from expression, vaccination efficacy depends on DNA delivery. DNA immunogens are generally administered by intramuscular or intradermal injections, usually followed by electroporation, which enhances delivery 1000-fold. Other techniques are also used, such as noninvasive introduction by biojectors, skin applications with plasters and microneedles/chips, sonication, magnetofection, and even tattooing. An intense debate regarding the pros and cons of different routes of delivery is ongoing. A number of studies have compared the effect of delivery methods at the level of immunogen expression, and the magnitude and specificity of the resulting immune response. According to some, the delivery route determines immunogenic performance; according to others, it can modulate the level of response, but not its specificity or polarity. The progress of research aiming at the optimization of DNA vaccine design, delivery, and immunogenic performance has led to a marked increase in their efficacy in large species and humans. New DNA vaccines for use in the treatment of infectious diseases, cancer, allergies, and autoimmunity are forthcoming. This Special Issue covers various aspects of DNA vaccine development.

Medicine --- Epidemiology & medical statistics --- alphaviruses --- layered RNA/DNA vectors --- DNA vaccines --- RNA replicons --- recombinant particles --- tumor regression --- protection against tumor challenges and infectious agents --- ebola virus disease --- artificial T-cell antigens --- DNA vaccine constructs --- computer design --- gene expression --- immunogenicity --- DNA vaccine --- mRNA vaccine --- plasmid DNA --- in vitro transcribed mRNA --- immune responses --- formulations --- Cytolytic T Lymphocytes --- antibodies --- innate immunity --- adjuvants --- vaccine delivery --- plasmid --- cytolytic --- perforin --- bicistronic --- HCV --- HIV --- IL-36 --- adjuvant --- DNA --- Zika --- Epstein-Barr virus --- latent proteins --- LMP2 --- EBNA1 --- LMP1 --- HIV-1 --- enhancer element --- circovirus --- influenza --- immunization --- intranasal --- lipid --- flagellin --- BCG --- vaccine --- rBCG --- HTI --- T-cell --- AIDS --- clinical trial --- therapeutic vaccine --- hepatitis C virus (HCV) --- mesenchymal stem cells (MSC) --- modified MSC --- DNA immunization --- nonstructural HCV proteins --- immune response --- HCV vaccine --- myeloid derived suppressor cells (MDSCs)

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RNA viruses cause animal, human, and zoonotic diseases that affect millions of individuals, as is being exemplified by the devastating ongoing epidemic of the recently identified SARS-Cov-2. For years vaccines have had an enormous impact on overcoming the global burden of diseases. Nowadays, a vast number of different approaches, from purified inactivated and live attenuated viruses, nucleic acid (DNA or RNA) based candidates, virus-like particles, subunit elements, and recombinant viruses are been employed to combat viruses. However, for many of them efficient vaccines are not yet available. This will probably change dramatically with the current Covid-19 pandemic, as a vast variety of vaccinology approaches are being tested against it, with hundreds of candidates under development, dozens of them already in clinical trials, a fact that is breaking records in vaccine development and implementation. This is becoming possible thanks to the enormous work carried out during years to have the bases for a quick response, even against unknown pathogens, in an impressive short time. Here, results obtained with different vaccine´s methodological approaches against human (HIV, HCV, HRV) animal (PRRSV, PEDV, FMDV, VHSV) and zoonotic (RVF, WNV), RNA viruses are presented by field experts.

Medicine --- artificial protein --- polyepitope B- and T-cell HIV-1 immunogen --- epitopes of broadly neutralizing HIV-1 antibodies --- peptide mimic of discontinuous epitope --- immunogenicity --- birds --- vaccines --- West Nile virus --- flavivirus --- herd immunity --- porcine epidemic diarrhea virus --- RNA interference --- processivity factor --- intestine epithelial cells --- N gene --- rotavirus nanoparticle vaccine --- gnotobiotic pigs --- FMDV --- peptide vaccine --- single dose --- amount --- pig --- VHSV --- non-virion (NV) --- transcriptome profiling --- rainbow trout --- immune pathways --- Rift Valley fever virus (RVFV) --- modified vaccinia Ankara (MVA) --- cellular response --- neutralizing antibodies --- Gn Gc glycoproteins --- passive serum:virus transfer --- hepatitis C virus --- neutralising antibodies --- animal models --- immune responses --- PRRSV Mosaic T-cell DNA vaccine VACV --- PRRS --- cross protection --- heterologous virus challenge