How can a new technology succeed where others have failed? COVID-19 mRNA vaccines are very effective against SARS-CoV-2, and the scientific community intends to use them against other diseases as well. But what’s new about mRNA vaccine technology?

The previous “record” in producing an effective vaccine against an infectious disease belonged to the mumps vaccine, developed in four years during the 1960s. This record was smashed by the race to produce an anti-COVID-19 vaccine that was developed in 42 days, then took several months for Clinical Phases I, II, and III, leading to the approval of the Pfizer-BioNtech and Moderna vaccines.

How was it possible to bring a new vaccine to market so early?

The main reasons are (here for more detail):

  • Exceptional investment by governments
  • Massive participation by researchers
  • Recruitment of exceptional numbers of people into clinical trials
  • Strategy of working in parallel in the vaccine validation phase, instead of sequentially
  • Extensive research already underway for more than 20 years on the use of mRNA vaccines

Focusing on this last point, we can say that the technology behind mRNA vaccines is being studied on several diseases, both viral and oncological. The main reason is that mRNA vaccines are extremely versatile and produced very rapidly. They don’t require a manipulation of the virus and are therefore also quite safe. Moreover, for their production, one can make use of the information entered into databases by researchers and then build the mRNA molecule in a test tube — without the virus even entering the laboratory. The synthesis of a DNA or RNA molecule is a technique that’s been known for a long time, and in the case of SARS-CoV-2 mRNA, it’s also quite simple because the molecule is 4284 nucleotides long (i.e. bricks that have to be placed in a row).

What happens once the mRNA molecule is synthesized?

The mRNA must be inserted into a lipid droplet that works like a “Trojan Horse”; in fact, it protects it and allows its introduction into the cells. RNA is a very labile molecule, so if it wasn’t protected by this envelope it would be immediately degraded by enzymes. This is well known by biologists who have already been studying it for many years.

Once penetrated into the cell, the lipid droplet releases mRNA that’s immediately used by ribosomes (which are protein factories within the cell) for the production of the Spike protein that in turn, is released outside the cell and stimulates the immune system to form the necessary antibodies, so as to be ready in case of infection by SARS-CoV-2.

The study of mRNA vaccines is not completely new. RNA vaccines have been studied for over twenty years. For example, there’s a vaccine against Zika virus that is in the Clinical Trial Phase, and other infectious agent diseases are being studied such as cytomegalovirus that causes neurological defects in infants, or respiratory syncytial virus that causes airway inflammation in infants, and other respiratory viruses such as metapneumovirus and a pathogen responsible for a parainfluenza.

Can it also play an important role against cancer?

Important research is also underway for the use of mRNA vaccines in oncology. In this field, the situation is more complex, since it’s necessary to know the genetic profile of both the normal cells of a patient and the tumor cells. Then, through a bioinformatic algorithm, the genetic profile is compared and the differences are identified, that allow the production of an mRNA (that is introduced by means of a lipid droplet in the patient’s cells), to provide the mold to ribosomes for the production of the protein that will stimulate the immune system against cancer cells.

This is an approach of Personalized Medicine, as the genetic profile of cancer cells is fairly different from patient-to-patient, so it involves many studies and very high associated costs.

Several pharmaceutical companies, including Moderna, BioNtech and CureVac, are developing such vaccines. In particular, back in 2017, BioNtech published work in a leading international scientific journal in which it demonstrated the efficacy of an mRNA vaccine administered to 13 people with advanced-stage melanoma. After treatment, the patients’ bodies developed an effective immune response against the tumor, and no other metastases appeared.

The road, already mapped out, is now easier to follow, thanks to the acceleration brought about by the studies on SARS-CoV-2, and these will soon lead to many other useful drugs and treatments to fight many (other) diseases.

This post is also available in: Italiano


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