Traditional or conventional vaccines exploit two approaches: either the introduction of live attenuated infectious agents that replicate within the host without causing disease or the introduction of specific antigens that trigger an immune response. Recently, a revolutionary strategy based on gene-based vaccines −either DNA- or RNA-based− has been proposed. This strategy involves the direct introduction of a DNA or RNA sequence encoding the antigen or antigens against which an immune response is sought, and relies on the in situ production of the target antigen (1). This means that the cell’s machinery uses the instructions contained in the introduced genetic material to make virus antigens that the immune system reacts to.
Gene-based vaccines present several advantages over traditional ones, including the stimulation of both B- and T-cell responses, improved vaccine stability even in the absence of a cold chain (for those vaccines based on DNA), absence of any infectious agent, and the relative ease of large-scale manufacture (1). Moreover, DNA- or RNA-based vaccines may even be effective against non-infectious conditions such as cancer and autoimmune diseases, where conventional vaccines are ineffective. Gene-based vaccines have been shown to generate immune responses against influenza virus, hepatitis B virus, human immunodeficiency virus (HIV), rabies virus, and malarial parasites, among others, in animals (1). DNA-plasmid vaccines are currently approved for veterinary uses, but not for human applications.
This approach could also speed up the discovery of a vaccine against coronavirus disease 2019 (COVID-19). Three different techniques based on DNA and RNA molecules are under clinical trials for COVID-19. The first is a DNA-plasmid vaccine encoding spike antigens under development at Inovio Pharmaceuticals (Plymouth Meeting, PA, US). This candidate has been developed based on a similar approach previously tested against the coronavirus causing Middle East respiratory syndrome (MERS).
A second approach skips the step of translation from the DNA plasmid to RNA by using RNA vaccines. RNA vaccines are considered to generate a stronger memory in the immune system than DNA vaccines, therefore requiring lower dosing (2). However, RNA vaccines are less stable than DNA ones, usually requiring refrigeration, which can be challenging in some settings. Several RNA vaccines are under evaluation in clinical trials for viral illnesses such as rabies, HIV, and Zika (2). Moderna (Cambridge, MA, US) is using this approach for COVID-19. A phase 3 clinical trial started on July 27th to evaluate if this vaccine candidate −called mRNA-1273− can prevent symptomatic COVID-19 (3). This trial is expected to enroll 30.000 healthy volunteers in the US.
A third approach being tested at Johnson & Johnson (New Brunswick, NJ, US) is the introduction of the DNA sequence encoding the antigen of interest into a non-replicating adenoviral vector (a common cold virus) (2). In total, there are currently more than 30 DNA- or RNA-based vaccine candidates being explored for COVID-19. Although no candidate vaccine for COVID-19 is a clear favorite yet, the results up to date are considered encouraging, with gene-based vaccines under experimentation showing great promise.
However, many aspects of the immune response caused by gene-based vaccines are not fully understood. Another challenge for their application is the fact that gene-based vaccines usually encode a single antigen, and therefore may require a combination of vaccines when an immune response against multiple proteins is required (4). Moreover, a careful evaluation of different delivery methods is still required. The World Health Organization clearly states that the value and advantages of DNA and RNA vaccines must be assessed on a case-by-case basis, with applicability depending on the nature of the disease, the antigen, and the type of protective immune response (1). Once all these aspects are taken into consideration, there is no doubt that gene-based vaccines will revolutionize future immunization strategies.
1. World Health Organization. DNA vaccines.
Accessed on 29th July 2020.
2. Charles Schmidt. Genetic Engineering Could Make a COVID-19 Vaccine in Months Rather Than Years.
Accessed on 29th July 2020.
3. National Institutes of Health. Phase 3 clinical trial of investigational vaccine for COVID-19 begins.
Accessed on 30th July 2020.
4. Abbany Zulfikar. What’s the science on DNA and RNA vaccines? Accessed on 30th July 2020.
Laura Moro, Ph.D., is a researcher and science & medical writer particularly interested in infectious diseases, global health, and health innovation. She conducted research for several years on the immunopathology and diagnosis of malaria in Sub-Saharan Africa. In 2015 she received a Marie Curie postdoctoral award to work in the interface between the academia and the industry for the design of novel diagnostic devices. She is the co-founder of AI Scope, a non-profit organization using artificial intelligence to improve the diagnosis of infectious diseases in low-resource settings. She believes in the power of science (and scientists) to improve our world.
Having worked in the biotech field, Laura joined the Communication Task Force of YEBN in 2020 to support the Newsletter with her science journalist expertise.