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Vaccination is a crucial preventative measure to protect against disease and has helped to eradicate epidemics like smallpox and polio. They enable our bodies to respond more effectively to infection by mimicking the structure of the infectious agent. RNA (sometimes referred to as messenger RNA or mRNA) vaccines, are a new type of vaccine that has recently been developed. They rely on a different way to mimic infection to induce an immune cell response. In comparison to other vaccines they are more robust, more versatile, and yet, equally efficient. RNA vaccine technology is a promising new field that can potentially prevent and treat a wide range of diseases including coronavirus (SARS-COVID-2).
You may have already heard about the burgeoning era of vaccinology? This kind of technology made headlines in the news recently when the Bill & Melinda Gates Foundation invested $52 million in CureVac, which specialises in RNA vaccine development. So, how do RNA vaccines work, how are large scale vaccines developed, what are their applications and what are their main advantages compared to traditional methods?
How do RNA vaccines work?
Vaccination is a process by which target molecules named, antigens, are deliberately introduced into the body in order to stimulate the immune system. Antigens are particles of infectious agents that have been inactivated so as not to cause disease. Exposure to specific antigenic particles leads to antibody production. Antibodies are proteins, which endow the body with a kind of memory or acquired immunity for a specific pathogen and enable the immune system to more effectively recognise and respond to a real infection with an active pathogen.
Vaccine production is a long and complex process, and it has been difficult to effectively implement vaccination technology against certain viral proteins and pathogens. Advances in next generation sequencing technologies are improving the speed with which they can be produced.
For conventional vaccines, a protein antigen molecule is introduced in the body to produce a response from immune cells. However, in the case of RNA or DNA vaccines, no antigen is introduced, only the DNA or RNA sequence containing the genetic information to produce the antigen. They can be injected in various ways (under the skin, in the vein or in lymph nodes) and then they can enter our body’s cells. Those cells will use the RNA sequence of the antigen for antigen synthesis. The antigen is then localised to the surface of a cell and triggers the activation of the immune system.
How are they produced?
With the considerable progress in DNA sequencing, it has become relatively easy to determine the genome sequence of pathogens that cause infectious disease. RNA (also known as messenger RNA) can thus be produced in vitro, i.e. outside the cells, using a DNA template containing the sequence of a specific antigen. Creating a RNA vaccine also requires some engineering of the RNA to achieve a strong expression of the antigen.
The production of RNA vaccines is faster than that of classical versions. RNA vaccines may be effective against pandemics because they also provide more flexibility to prevent or treat pathogens that are rapidly evolving. If we take the example of influenza, the therapeutics have to be designed each year to recognise specific strains that are most likely to cause disease in the coming season. However, these forecasts have not always been accurate, such as during the winter of 2014-2015, making the influenza vaccine less protective. The World Health Organization estimates it takes approximately five to six months to produce such a therapeutic, whereas the company CureVac claims that RNA vaccines could be manufactured in less than two months at a lower production cost, making it possible to respond to epidemics even as they develop. Therefore, RNA-based products offer a comparatively simple and rapid solution to unpredictable, rapidly evolving pathogens.
What is the current state of the research?
This new exciting technology could be applied to many diseases, and pharmaceutical companies are making major investments in that area. RNA vaccines are still at the pre-clinical or clinical stage, but have yielded promising results. Below, we will explore two examples with the most advanced results: RNA vaccines to treat cancer and to prevent influenza.
In the field of cancer immunotherapy, “cancer vaccines” take advantage of the expression of specific markers by cancer cells to direct the immune response and attack the tumor. RNA-based products against prostate cancer, melanoma, and lung cancer (non-small cell lung cancer) are currently in clinical trials. As of 2020 there are currently no RNA vaccines approved for cancer treatment. However, six different RNAs against proteins produced in excess in tumor cells were used to formulate a trial version against lung cancer. By taking advantage of the flexibility of RNA vaccine production, scientists can thus produce a therapeutic with different antigens which is consequently better at targeting the tumor cells. Interestingly, because of the versatility of RNA vaccines, they could be designed to match the antigen repertoire of individual patient tumors. Tumor cells are very different between patients, and this variability is an ongoing issue for cancer treatment. RNA vaccines could be a step in the path towards personalised medicine in this respect.
RNA vaccines are also being developed to prevent infectious diseases. A product against rabies is currently in clinical trials, while vaccines against influenza, HIV or tuberculosis are still at the research stage. Published results with the influenza vaccine showed promising protection in mice. Indeed, injection of RNA coding for different proteins of the influenza virus induced the production of antibodies, and when the mice were later exposed to the virus, all survived. The results of these pre-clinical trials bode well for potential clinical trials in the future.
This era in vaccinology including RNA vaccines is still nascent. However, RNA vaccines appear to be a promising technology worth keeping an eye out for.
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