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Taming the Enemy
Published in Norman Begg, The Remarkable Story of Vaccines, 2023
DNA vaccines contain the genetic material that has the code for the antigen of the vaccine, the part that stimulates an immune response. A DNA vaccine is either inserted into the gene of a harmless virus before injection or injected directly. Vaccines that use a harmless virus as the carrier for the genetic material are called viral vector vaccines. The genetic material for the virus is inserted into the harmless virus, which acts as a vector (the medical term for a carrier). The viral vector may sometimes replicate, but does not cause disease. Several of the COVID-19 vaccines are viral vector vaccines, including the one developed at Oxford University with AstraZeneca, the Johnson & Johnson vaccine, and my favourite – simply because of its name – Sputnik V. These COVID-19 vaccines use an adenovirus, one of the causes of the common cold, as the vector to carry the genetic information in the vaccine. A useful feature of viral vector vaccines is that the same vector can be used to make different vaccines. The adenovirus vector that is used for Johnson & Johnson’s COVID-19 vaccine had already been used to make a highly effective Ebola vaccine a few years earlier.
Vaccine Development Strategies and the Current Status of COVID-19 Vaccines
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Mohsen Akbarian, Kenneth Lundstrom, Elrashdy M. Redwan, Vladimir N. Uversky
The first DNA-based vaccines were already developed in 1983. DNA vaccines are based on plasmid DNA expressing antigens for the vaccine targets in transfected host cells. DNA plasmids are relatively stable and can replicate independently in host cells. However, low transfection efficacy and the need for delivery to the nucleus has hampered their efficacy as vaccine vectors. To address these issues, electroporation, jet injection, gene gun, and nanoparticle technologies have been applied. Numerous types of nanoparticles, such as lipid and polymer nanoparticles, lipid-polymer hybrid nanoparticles, DNA-polymer complexes, nanoparticles coated with polymeric materials and gold, and protein-DNA complexed nanoparticles have been formulated for improved DNA delivery [48]. MERS-CoV S and N proteins have been expressed from DNA plasmid as vaccine antigens [49]. Effective and specific immunogenic responses, including the production of γ-interferon, IL-2, CD4+, CD8+, and IL-2, and the induction of cytotoxic T lymphocytes have been reported in animal studies. One of the most important advantages is that production of plasmid DNA in bacteria is rapid and inexpensive [50]. Other important advantages are the possibility of combining DNA-based vaccines with other vaccine platforms (such as first generation vaccines), excellent heat and shelf-life stability, ease of DNA sequence engineering and reduced safety risk compared to viral vectors [48]. However, limited immune responses caused by low transfection efficiency of DNA vaccines is a disadvantage [19].
Adaptive humoral immunity and immunoprophylaxis
Published in Gabriel Virella, Medical Immunology, 2019
DNA vaccines. The observation that intramuscular injection of nonreplicating plasmid DNA encoding the hemagglutinin (HA) or nucleoprotein (NP) of influenza virus elicited humoral and cellular protective reactions attracted enormous interest from the scientific community. The recombinant DNA is taken up by APCs at the site of injection and is presented to T helper cells in a way that both humoral and cell-mediated immune responses are elicited. The safety and easy storage of candidate DNA vaccines are extremely appealing, and several different trials are ongoing. However, the initial impression from human trials is that DNA vaccines are far less potent in humans than they appear to be in experimental animals.
Insight into the current Toxoplasma gondii DNA vaccine: a review article
Published in Expert Review of Vaccines, 2023
Xirui Zhang, Hao Yuan, Yasser S. Mahmmod, Zipeng Yang, Mengpo Zhao, Yining Song, Shengjun Luo, Xiu-Xiang Zhang, Zi-Guo Yuan
To avoid the above-mentioned safety issues while trying to achieve a better immune effect, many researchers worked hard towards a more advantageous type of vaccine, the so-called ‘DNA vaccine.’ A great merit of DNA vaccines is that they are highly malleable and can be designed with one or more T. gondii genes at our will. So, in theory, we could design vaccines that elicit more significant Th1 immune responses against T. gondii infection and, hopefully, even tailor a vaccine that brings complete protection against all three life stages of T. gondii [13,14]. Additionally, the DNA sequence of the recombinant plasmid has been thoroughly studied to avoid any potential risks and can be massively produced at a fairly low cost [14]. On top of that, DNA vaccines would cause no allergic reaction, and therefore, the vaccination route can be flexibly adapted. Since they are non-livings, they do not even require cold-chain storage and hence, it could be easier to have them stored and transported [15]. To sum up, in theory, DNA vaccines can achieve better immune effects through purposeful design and avoid safety issues while saving costs in production, storage, and transportation [15].
The baculovirus expression vector system: a modern technology for the future of influenza vaccine manufacturing
Published in Expert Review of Vaccines, 2022
Claudia Maria Trombetta, Serena Marchi, Emanuele Montomoli
Even DNA vaccine seems to be a promising technology in development since the 1990’. These vaccines do not require the growth of live virus, are temperature stable, noninfectious, non-replicating and the production process is rapid and cheap. The great advantage is that the target sequences of clinical isolates can be used as soon as available and are able to induce both humoral and cellular immune responses. The route of administration is critical and different devices have been evaluated, such as patches, gene-gun, and electroporation. The main concerns are with regard to safety and the potential integration of the plasmid DNA into host genome, the development of anti-DNA antibodies resulting in auto-immune disease and antibiotic resistance [108–113]. However, a phase 1 randomized clinical trial in children and adolescents priming with trivalent DNA vaccine and boosting with trivalent IIV provided evidence that the strategy is safe and well tolerated [114]. So far, no DNA vaccines have been approved for use in humans.
Cancer vaccines as a targeted immunotherapy approach for breast cancer: an update of clinical evidence
Published in Expert Review of Vaccines, 2022
Maryam Abbaspour, Vajihe Akbari
DNA vaccines are bacterial plasmids generated to deliver TA-encoding genes that create or enhance an adaptive immune response to TA-bearing tumor cells [120]. The main strength of DNA vaccines is that they can activate CD4 and CD8 T cells as well as indirectly the humoral immunity by providing antigens encoded by MHC class I and class II [121]. So far, there are no approved DNA vaccines for use in humans and they are undervaluation in phase I or II clinical studies. To enhance efficient immune responses of DNA vaccines, a plasmid delivery system was optimized and they were often developed in combination with other vaccines platforms therapies. The most common methods used to increase transfection efficiencies, such as localized delivery system, electroporation, sonication, and gene gun, can overcome the barriers (intra- or extracellular) to DNA transfer [122,123]. To induce protein synthesis, DNA requires passing through the nuclear membrane. DNA vaccines can integrate into the host genome leading to insertional mutagenesis, chromosomal instability, and oncogenic transformation. The expression of DNA-encoded proteins can be taken place over months to years, depending on vector [124].