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 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.
Highlights
Background for Nucleic Acid (NA) Vaccines. It has been three decades since Felgner and colleagues published that nucleic acid constructs, i.e., both plasmid DNA and mRNA could be directly injected in vivo into mice resulting in the encoded protein made in situ [1]
Since many vaccines work via antibody responses, at least in terms of demonstrating a correlate of efficacy, DNA vaccines, while capable of stimulating antibodies, are considered more effective for cytotoxic T lymphocytes (CTL) and T helper cells than for antibody responses
The West Nile virus (WNV) vaccine results pointed towards the importance of the antigen being a highly immunogenic protein, since one difference between the WNV vaccine and other vaccines is that the WNV plasmid vaccine encodes both the premembrane and surface envelope (E) antigens which form a subviral particle that is virus-like when produced in cells, with the resulting structure having antigenic properties like the regular infectious virion [12]
Summary
It has been three decades since Felgner and colleagues published that nucleic acid constructs, i.e., both plasmid DNA and mRNA could be directly injected in vivo into mice resulting in the encoded protein made in situ [1]. Because the plasmid DNA transfected muscle cells, which are not professional antigen presenting cells (APCs), and these muscle cells could produce the encoded protein antigen, the question was raised as to whether a DNA vaccine would induce tolerance against an antigen These concerns were put to rest through extensive pre-clinical studies and clinical trials. Quite the opposite was seen—strong immune responses against foreign pathogen antigens and tumor antigens could be generated, while therapy of autoimmune diseases such as diabetes [9] and multiple sclerosis [10] looked promising in early phase human clinical trials These studies paved the way for future NA vaccines, namely mRNA vaccines, as, for example, concerns about autoimmunity and tolerance and potential limits of immune responses due to production of antigen by non-APCs have not been considered crucial. Viruses 2021, 13, 258 for both humans and animals are crucial for anticipating, preventing, and responding to novel pathogens
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