Although the subject of research for more than 30 years, messenger RNA (mRNA) technology still seemed far from becoming a reality. However, with the pandemic and the investment never seen before in the history of vaccines, two unprecedented achievements came to the area: the first immunizers with innovative technology to be approved and applied on a large scale, and the production of vaccines developed in record time, in less than a year.
Now, that in addition to being consolidated and safe, the technology has proven to be highly effective, strategies are already being tested with the technique for the unprecedented prevention of diseases such as HIV, zika, ebola, herpes, in addition to new, more effective vaccines for tuberculosis, malaria, dengue. it’s flu. There are even promising studies that implement mRNA to fight cancer and diagnoses such as diabetes and sickle cell anemia. The researchers chart an optimistic scenario for major scientific advances in the next decade.
And Brazil should gain prominence with its own production of immunizations and therapies that adopt the technology. In Bahia, a new vaccine against Covid-19 is already being developed using the platform, by scientists from Senai Cimatec, which is in clinical trials.
In 2021, Bio-Manguinhos, from Fiocruz, was chosen by the World Health Organization (WHO) as part of a global selection to encourage the creation of mRNA immunizations. In addition to also developing a new vaccine for Covid-19 with the technology, the institute researches therapies for cancer and prevention of other diseases.
“We had been working with mRNA technology for a few years, mainly focused on therapeutic vaccines for the treatment of cancer, but with the pandemic we also started to develop our own mRNA Covid-19 vaccine, which is in testing.
This technology had been under study for decades, but it took this leap with the health crisis and proved to be very effective. Now we hope that we will have similar positive results with other diseases”, says the deputy director of Technological Development of Bio-Manguinhos, Sotiris Missailidis.
The high expectations involving messenger RNA are due to a few factors. The first one is the way of acting. Basically, it is a code with instructions for the body’s cells to produce a certain protein.
In the case of Covid-19 vaccines, instead of the immunizer introducing the inactivated virus or a part of it for the immune system to produce the defenses, the mRNA uses the organism itself as a “factory” for the coronavirus S protein, which is then handled by the body to produce defense cells and antibodies.
“Without a doubt, mRNA has revolutionized vaccinology, because through a code you can lead the individual who receives the vaccine to produce his own protein. This is a revolution because it allows us to produce proteins against anything, then antibodies against some disease, proteins that prevent tumors, degenerative diseases.
In theory, the technology is applicable for diabetes, Alzheimer’s, cancer, not just infectious diseases. It is a hope for many other diseases for which we either do not have a vaccine or that we need better alternatives”, explains infectious disease specialist and director of the Brazilian Society of Immunizations (SBIm), Renato Kfouri.
He says that, since 1990, the platform has been studied, but it was considered unstable in tests. The situation changed in 2005, when a team of American researchers developed fat capsules, called liposomes, which surround the mRNA and manage to take it fully into the body.
One of the scientists responsible for the discovery even wrote an article in the scientific journal Nature Reviews Drug Discovery, in 2018, entitled “mRNA Vaccines – A New Era in Vaccinology”, in which he listed a series of studies with promising results from the technology.
Neglected diseases are focus at Fiocruz
Missailidis, from Fiocruz, highlights that, although the production of vaccines with the new technology is starting mainly in foreign countries, eventually Bio-manguinhos may become autonomous in the manufacture of mRNA therapies.
“Our biggest problem was having the ability to develop new technologies without depending on the United States, Europe, countries that normally arrive with products first and then transfer technology.
The effort we are making right now is to change this paradigm. And we can use mRNA for rare diseases, neglected diseases, which are often not of interest to large pharmaceutical companies, but which Fiocruz, as a public institution, has the mission of being able to serve this part of the population”, says the deputy. director of Technological Development of Bio-manguinhos.
Fiocruz’s new immunizer for Covid-19 mRNA, which should begin clinical trials early next year, also has the differential of awakening the immune response not only with the S protein of the coronavirus, but also with N. Sotiris, the second protein is more conserved, so it is expected to offer greater immunity to protect against new variants.
There is also the development of the technology by Senai Cimatec, in Bahia, in partnership with the company HDT Bio Corp, from the United States.
The infectious disease specialist and chief researcher at the institution, Roberto Badaró, who is leading the research, explains that the mRNA vaccine also uses an unprecedented nanoparticle capable of protecting the molecule and increasing absorption in the body, and celebrates the project as an important step towards the domain of the platform in Brazil. “Today we have the capacity to manufacture this vaccine here in Brazil, we incorporated this technology there at Senai Cimatec and we are finishing the phase 1 studies.
This platform is a big revolution, so we are very excited that Brazil will have a competitive participation in the international scenario of a modern vaccine”, says Badaró. He says that there is an immunizer with the technology also being tested for leishmaniasis, a disease caused by a protozoan and transmitted by mosquitoes that, if left untreated, can be highly fatal.
“Thousands of people acquire leishmaniasis in Brazil and Latin America, which is a disfiguring disease that, when it affects the nasal mucosa, destroys the nose, being a serious disease, but not receiving much attention because it is tropical. But this technology will help us make several other vaccines against other diseases”, adds the infectious disease specialist.
Badaró, from Senai Cimatec, says that there are still therapeutic vaccines under development at the institution for breast, prostate and ovarian cancer, which should gain momentum after the end of tests with the immunizer for Covid-19. The fight against tumors is in fact one of the great promises for the advancement of technology, explains oncologist Ramon Andrade de Mello.
IMMUNIZANTS UNDER TEST
In addition to the broad potential, mRNA vaccines have demonstrated superior efficacy to conventional models and have the potential to be manufactured at a lower cost. This is because, as the platform is synthetic, and does not involve live viruses, it does not require, for example, a biosafety laboratory.
In addition, they can be developed and adapted more quickly, which made it possible for Covid-19 immunizers to start clinical trials less than six months after Sars-CoV-2 was discovered in China in 2019.
One of the most awaited results for the new generation of vaccines that are starting to be tested is that of the immunizing agent against HIV. This year, Moderna – a pharmaceutical company created with a focus on mRNA and responsible for one of the Covid-19 vaccines – began phase 1 of clinical trials with some candidates.
Studies with an immunizing agent for Nipah henipavirus (NiV), a highly lethal pathogen, originally from animals, which causes occasional outbreaks in humans in India and Bangladesh, are also in the first stage.
However, these should not be the next to come out of paper. The laboratory is also conducting tests with a vaccine for the Zika virus, which are already in phase 2, and for a new version of the immunizing agent against the Influenza virus, which causes the flu, which is in phase 3.
There are also studies for joint versions of the flu vaccine with that of Covid-19 and protection for the respiratory syncytial virus (RSV), a microorganism that causes a high number of hospitalizations and deaths in young children and cannot yet be fought with immunizations.