Nucleic Acid Vaccines

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (15 January 2021) | Viewed by 27765

Special Issue Editors


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Guest Editor
Leids Universitair Medisch Centrum, Leiden, The Netherlands
Interests: virology; bacteriology; infectious diseases; vaccines; oncology

E-Mail Website
Guest Editor
Universiteit Utrecht, Utecht, Netherlands
Interests: virology; coronaviruses; infectious diseases; vaccines; pathogenesis

Special Issue Information

Dear Colleagues,

Nucleic acids constitute a relatively new type of vaccine. DNA vaccines date back to the early 1990s with the discovery that plasmid DNA, delivered via muscle or skin, induces an antibody response to the encoded protein. The DNA has to cross the membranes of the cell and the nucleus. Subsequently, the antigen is synthesized and an immune response is mounted. The development of RNA vaccines, consisting of mRNA, started 10 years later. mRNA has to cross one membrane only but is extremely sensitive to degradation by endonucleases. Therefore, a formulation, e.g., liposomes, that protects the RNA is needed. In addition to antibodies, DNA and RNA vaccines elicit CD4+ and CD8+ T cells. Logistically, these vaccines have many advantages, such as fast, inexpensive and scalable production and short development times. Moreover, no handling of infectious virus is required during vaccine development. This makes these vaccines ideal for protection against emerging viral diseases. Presently, vaccines against cancer and various infectious diseases are under development. No vaccines have been licensed yet, but nucleic acid vaccines are among the lead COVID-19 vaccine candidates. This Special Issue will give a complete picture of the state of the art in nucleic acid vaccine development.

Prof. Dr. B.A.M. (Ben) van der Zeijst
Prof. Dr. P.J.M. (Peter) Rottier
Guest Editors

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Keywords

  • DNA vaccines
  • RNA vaccines
  • vaccine production
  • vaccine delivery
  • cancer therapy
  • vaccine development
  • emerging infections
  • COVID-19

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Published Papers (4 papers)

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Research

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10 pages, 912 KiB  
Article
Lipofection with Synthetic mRNA as a Simple Method for T-Cell Immunomonitoring
by Natalia Teresa Jarzebska, Julia Frei, Severin Lauchli, Lars E. French, Emmanuella Guenova, Cécile Gouttefangeas, Thomas M. Kündig, Mark Mellett and Steve Pascolo
Viruses 2021, 13(7), 1232; https://doi.org/10.3390/v13071232 - 25 Jun 2021
Cited by 1 | Viewed by 3883
Abstract
The quantification of T-cell immune responses is crucial for the monitoring of natural and treatment-induced immunity, as well as for the validation of new immunotherapeutic approaches. The present study presents a simple method based on lipofection of synthetic mRNA in mononuclear cells as [...] Read more.
The quantification of T-cell immune responses is crucial for the monitoring of natural and treatment-induced immunity, as well as for the validation of new immunotherapeutic approaches. The present study presents a simple method based on lipofection of synthetic mRNA in mononuclear cells as a method to determine in vitro T-cell responses. We compared several commercially available transfection reagents for their potential to transfect mRNA into human peripheral blood mononuclear cells and murine splenocytes. We also investigated the impact of RNA modifications in improving this method. Our results demonstrate that antigen-specific T-cell immunomonitoring can be easily and quickly performed by simple lipofection of antigen-coding mRNA in complex immune cell populations. Thus, our work discloses a convenient solution for the in vitro monitoring of natural or therapy-induced T-cell immune responses. Full article
(This article belongs to the Special Issue Nucleic Acid Vaccines)
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21 pages, 3797 KiB  
Article
Multivalent DNA Vaccines as a Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses
by Jingjing Jiang, Stephanie J. Ramos, Preeti Bangalore, Dustin Elwood, Kathleen A. Cashman, Sagar B. Kudchodkar, Katherine Schultheis, Holly Pugh, Jewell Walters, Jared Tur, Jian Yan, Ami Patel, Kar Muthumani, Connie S. Schmaljohn, David B. Weiner, Laurent M. Humeau and Kate E. Broderick
Viruses 2021, 13(3), 382; https://doi.org/10.3390/v13030382 - 27 Feb 2021
Cited by 11 | Viewed by 4380
Abstract
The emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. Outbreaks of Ebola, Lassa, and Marburg viruses in overlapping regions of central and West Africa and the co-circulation of Zika, Dengue, and Chikungunya [...] Read more.
The emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. Outbreaks of Ebola, Lassa, and Marburg viruses in overlapping regions of central and West Africa and the co-circulation of Zika, Dengue, and Chikungunya viruses in areas with A. aegypti mosquitos highlight the need for a rapidly deployable, safe, and versatile vaccine platform readily available to respond. The DNA vaccine platform stands out as such an application. Here, we present proof-of-concept studies from mice, guinea pigs, and non-human primates for two multivalent DNA vaccines delivered using in vivo electroporation (EP) targeting mosquito-borne (MMBV) and hemorrhagic fever (MHFV) viruses. Immunization with MMBV or MHFV vaccines via intradermal EP delivery generated robust cellular and humoral immune responses against all target viral antigens in all species. MMBV vaccine generated antigen-specific binding antibodies and IFNγ-secreting lymphocytes detected in NHPs up to six months post final immunization, suggesting induction of long-term immune memory. Serum from MHFV vaccinated NHPs demonstrated neutralizing activity in Ebola, Lassa, and Marburg pseudovirus assays indicating the potential to offer protection. Together, these data strongly support and demonstrate the versatility of DNA vaccines as a multivalent vaccine development platform for emerging infectious diseases. Full article
(This article belongs to the Special Issue Nucleic Acid Vaccines)
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Review

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12 pages, 790 KiB  
Review
Synthetic Messenger RNA-Based Vaccines: From Scorn to Hype
by Steve Pascolo
Viruses 2021, 13(2), 270; https://doi.org/10.3390/v13020270 - 9 Feb 2021
Cited by 58 | Viewed by 14348
Abstract
In the race for a vaccine against SARS-CoV-2, the synthetic mRNA format has been shown to be the fastest one and proved to be safe and highly efficient, even at the very low dose of a few µg per injection. The mRNA vaccines [...] Read more.
In the race for a vaccine against SARS-CoV-2, the synthetic mRNA format has been shown to be the fastest one and proved to be safe and highly efficient, even at the very low dose of a few µg per injection. The mRNA vaccines are not new: vaccines that are based on attenuated mRNA viruses, such as Mumps, Measles, and Rubella, immunize by delivering their mRNAs into the cells of the vaccinated individual, who produces the viral proteins that then prime the immune response. Synthetic mRNA in liposomes can be seen as a modern, more refined, and thereby a safer version of those live attenuated RNA viruses. The anti-COVID-19 mRNA vaccine (coding the SARS-CoV-2 spike protein) is the third synthetic RNA therapeutic being approved. It follows the aptamer Macugen® (which neutralizes VEGF) and the siRNA Onpattro® (which destroys the transthyretin-coding mRNA). Remarkably, the 30 µg of mRNA that are contained in the first approved anti-COVID-19 vaccine are sufficient for generating high levels of neutralizing antibodies against the virus in all injected volunteers (including participants over 65 years old). The efficacy and safety data are stunning. The distribution of these vaccines throughout the world will bring a halt to the coronavirus pandemic. Full article
(This article belongs to the Special Issue Nucleic Acid Vaccines)
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15 pages, 313 KiB  
Review
The Key Role of Nucleic Acid Vaccines for One Health
by Anders Fomsgaard and Margaret A. Liu
Viruses 2021, 13(2), 258; https://doi.org/10.3390/v13020258 - 8 Feb 2021
Cited by 21 | Viewed by 4138
Abstract
The ongoing SARS-CoV-2 pandemic has highlighted both the importance of One Health, i.e., the interactions and transmission of pathogens between animals and humans, and the potential power of gene-based vaccines, specifically nucleic acid vaccines. This review will highlight key aspects of the development [...] Read more.
The ongoing SARS-CoV-2 pandemic has highlighted both the importance of One Health, i.e., the interactions and transmission of pathogens between animals and humans, and the potential power of gene-based vaccines, specifically nucleic acid vaccines. This review will highlight key aspects of the development of plasmid DNA Nucleic Acid (NA) vaccines, which have been licensed for several veterinary uses, and tested for a number of human diseases, and will explain how an understanding of their immunological and real-world attributes are important for their efficacy, and how they helped pave the way for mRNA vaccines. The review highlights how combining efforts for vaccine development for both animals and humans is crucial for advancing new technologies and for combatting emerging diseases. Full article
(This article belongs to the Special Issue Nucleic Acid Vaccines)
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