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      A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

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          Abstract

          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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          Type I interferons (alpha/beta) in immunity and autoimmunity.

          Argyrios Theofilopoulos, Roberto Baccala, Bruce Beutler … (2005)
          The significance of type I interferons (IFN-alpha/beta) in biology and medicine renders research on their activities continuously relevant to our understanding of normal and abnormal (auto) immune responses. This relevance is bolstered by discoveries that unambiguously establish IFN-alpha/beta, among the multitude of cytokines, as dominant in defining qualitative and quantitative characteristics of innate and adaptive immune processes. Recent advances elucidating the biology of these key cytokines include better definition of their complex signaling pathways, determination of their importance in modifying the effects of other cytokines, the role of Toll-like receptors in their induction, their major cellular producers, and their broad and diverse impact on both cellular and humoral immune responses. Consequently, the role of IFN-alpha/beta in the pathogenesis of autoimmunity remains at the forefront of scientific inquiry and has begun to illuminate the mechanisms by which these molecules promote or inhibit systemic and organ-specific autoimmune diseases.
          Article 0 comments Cited 314 times – based on 0 reviews     Review now
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            New Vaccine Technologies to Combat Outbreak Situations

            Susanne Rauch, Edith Jasny, Kim Schmidt … (2018)
            Ever since the development of the first vaccine more than 200 years ago, vaccinations have greatly decreased the burden of infectious diseases worldwide, famously leading to the eradication of small pox and allowing the restriction of diseases such as polio, tetanus, diphtheria, and measles. A multitude of research efforts focuses on the improvement of established and the discovery of new vaccines such as the HPV (human papilloma virus) vaccine in 2006. However, radical changes in the density, age distribution and traveling habits of the population worldwide as well as the changing climate favor the emergence of old and new pathogens that bear the risk of becoming pandemic threats. In recent years, the rapid spread of severe infections such as HIV, SARS, Ebola, and Zika have highlighted the dire need for global preparedness for pandemics, which necessitates the extremely rapid development and comprehensive distribution of vaccines against potentially previously unknown pathogens. What is more, the emergence of antibiotic resistant bacteria calls for new approaches to prevent infections. Given these changes, established methods for the identification of new vaccine candidates are no longer sufficient to ensure global protection. Hence, new vaccine technologies able to achieve rapid development as well as large scale production are of pivotal importance. This review will discuss viral vector and nucleic acid-based vaccines (DNA and mRNA vaccines) as new approaches that might be able to tackle these challenges to global health.
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              Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial.

              Cornelia Trimble, Matthew P Morrow, Kimberly Kraynyak … (2015)
              Despite preventive vaccines for oncogenic human papillomaviruses (HPVs), cervical intraepithelial neoplasia (CIN) is common, and current treatments are ablative and can lead to long-term reproductive morbidity. We assessed whether VGX-3100, synthetic plasmids targeting HPV-16 and HPV-18 E6 and E7 proteins, delivered by electroporation, would cause histopathological regression in women with CIN2/3.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Vaccines (Basel)
                Journal ID (iso-abbrev): Vaccines (Basel)
                Journal ID (publisher-id): vaccines
                Title: Vaccines
                Publisher: MDPI
                ISSN (Electronic): 2076-393X
                Publication date (Electronic): 24 April 2019
                Publication date Collection: June 2019
                Volume: 7
                Issue: 2
                Electronic Location Identifier: 37
                Affiliations
                ProTherImmune, 3656 Happy Valley Road, Lafayette, CA 94549, USA; Liu@ 123456ProTherImmune.com
                Article
                Publisher ID: vaccines-07-00037
                DOI: 10.3390/vaccines7020037
                PMC ID: 6631684
                PubMed ID: 31022829
                SO-VID: 1bcb072e-b170-4a71-b615-ce771a90db30
                Copyright © © 2019 by the author.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 07 March 2019
                Date accepted : 19 April 2019
                Categories
                Subject: Review

                Keywords: dna vaccine,mrna vaccine,plasmid dna,in vitro transcribed mrna,immune responses,formulations,cytolytic t lymphocytes,antibodies,innate immunity
                Data availability:
                Keywords: dna vaccine, mrna vaccine, plasmid dna, in vitro transcribed mrna, immune responses, formulations, cytolytic t lymphocytes, antibodies, innate immunity

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