DNA vaccines

DNA vaccines are considered third generation vaccines (Ghaffarifar F 2018). DNA vaccines consist of a piece of DNA inserted into a bacterial plasmid or a non-infectious virus that encodes the antigen and is taken up and read in the target cell after injection of the vaccine (Saade F et al 2012). Plasmid is a circular piece of DNA used by a bacterium to store and share genes. Plasmids can replicate independently of the main chromosomal DNA and thus provide a simple tool for transferring genes between cells. For this reason, they are already an established system in the field of genetic engineering.

Once the DNA is introduced into the cell, the DNA antigen blueprint is transcribed into mRNA in the nucleus. The mRNA leaves the nucleus and is translated into the corresponding viral protein in the cytoplasm. This is usually a surface protein of the pathogen. This protein is then incorporated into the envelope of the cell and presented as a "foreign protein" at the cell surface MHC I and MHC II. At the cellular level, this simulates a symptomless infection in the host body, which triggers a specific immune response. This response includes, among others, antibody-producing B cells and helper T cells that support antibody production.

The immunogenicity of DNA vaccines is comparatively low, so that, as things stand, repeat immunizations are necessary, without which the long-term effects would not be sufficiently assured (Saade F et al. 2012). Furthermore, DNA vaccines usually require suitable adjuvants and appropriate carrier systems (liposomes, micro- or nanoparticles) to enhance their immunogenicity (Li L et al. 2016).

The data on possible side effects is currently still very limited.

The efficacy of the vaccine is influenced by the route of immunisation, with intracutaneous injection of the plasmid proving significantly more effective than intramuscular or subcutaneous injection, even at lower doses. Various technologies have been developed to aid this process - for example, electroporation, which uses short pulses of electrical current to create temporary pores in the cell membranes of patients (Hirao LA et al 2008). Encapsulating DNA in nanoparticles designed to fuse with the cell membrane also enhances this process (Ghaffarifar F 2018).

A potential safety hazard could be accidental integration of plasmidic DNA into the host genome (Robertson JS et al. 2000). This integration could lead to hypothetical activation of oncogenes or deactivation of tumor suppressor genes, as well as possible induction of autoimmune diseases against the DNA. To date, there is no evidence for the development of tumors or lupus erythematosus following plasmid immunizations in vivo.

DNA vaccines against influenza, AIDS, hepatitis B and hepatitis C, rabies are currently being researched. So far, however, DNA vaccines have only been approved for use in veterinary medicine. Meanwhile, therapeutic DNA cancer vaccines are considered a very promising strategy to activate the immune system against tumor diseases such as T-cell leukemias as well as cervical carcinoma (Lopes A et al. 2019).

1. Ghaffarifar F (2018) Plasmid DNA vaccines: where are we now? Drugs Today (Barc) 54: 315-333.
2. Hirao LA et al (2008) Combined effects of IL-12 and electroporation enhances the potency of DNA vaccination in macaques. Vaccine 26:3112-3120.
3. Li L et al. (2016) Molecular mechanisms for enhanced DNA vaccine immunogenicity. Expert Rev Vaccines 15:313-329.
4. Lopes A et al. (2019) Cancer DNA vaccines: current preclinical and clinical developments and future perspectives. J Exp Clin Cancer Res 38:146.
5. Robertson JS et al. (2000) European Union guidance on the quality, safety and efficacy of DNA vaccines and regulatory requirements. Dev Biol (Basel) 104:53-56.
6. Saade F et al (2012) Technologies for enhanced efficacy of DNA vaccines. Expert Rev Vaccines. 11:189-209.