Fátima Ventura, director of the Scientific Evaluation Unit at Infarmed, explains to Expresso how new scientific techniques and new verification procedures came together to produce what for many people seems like a miracle: vaccines obtained in record times. The expert tells how researchers and regulators managed to save time in each phase
Vaccines against covid-19 have already started to be administered in several countries, and are almost arriving in Portugal, less than a year after the start of the pandemic. The relative speed of its appearance, compared to the long periods associated with other vaccines of the past, generate suspicion in many people. In order to get treatment for the disease, aren’t dangerous shortcuts taken? Will the vaccine be effective? Won’t it have dangerous side effects?
To answer these questions, it is important to understand what this vaccine has new, in relation to others that we have been used to since childhood. Expresso spoke with Fátima Ventura, a pharmacist, director of the Scientific Evaluation Unit at Infarmed, and an evaluator herself. Ventura is also an alternate member of Portugal of the Committee for Medicinal Products for Human Use (CHMP), the last EU body that will give an opinion on vaccines in the EU before the European Commission.
Anticipating something said at the end of the conversation, it is not expected that life will return to what it was, or something like that, before the second half of 2021. Fátima Ventura refers to the prospect of a relatively normal winter, if all goes well. For the time being, he notes that, despite what the headlines suggest, the vaccines already approved in certain countries were for emergency use. “They have not yet been authorized for introduction to the market, either in the United Kingdom, the United States or Canada,” he says.
A NEW TECHNIQUE
To understand what makes many of the vaccines now developed different, it is essential to understand what distinguishes them from traditional vaccines. While an attenuated version of the pathogen in question, whether a virus or any other, is used, fragments of a genetic code are now involved. Specifically, that of the protein that appears in the images of the virus with the characteristic spike, or “peak”.
“When we administer this genetic code in a vaccine, our cells will translate that code into the virus protein”, explains Ventura. “As there is no genetic code behind the virus, this protein is not infectious. We are not going to get sick. What happens is something else. We have special cells, called antigen-presenting cells, that present this protein to other cells and will trigger the immune response: the production of antibodies that are expected to be neutralizing. That is, when the virus itself appears, they look at the protein that it brings and say: oh, it’s strange, I’m going to kill it. Basically, that’s it This protein is the way that the virus has to enter our cells. If the antibodies attack it, the virus does not bind to them and does not infect “.
Fátima Ventura refers to the six vaccines acquired by the EU – “or rather, with a proposal for acquisition, as they will only be effectively acquired if they are authorized”; two with messenger RNA, that of Moderna and that of BioNTech / Pfizer; that of the German company CureVac, which uses the same technique; one from SanofiPasteur-GSK; that of AstraZeneca and Johnson and Johnson, which use other viruses, the so-called adenoviruses, modified to not multiply in other cells and which also have the genetic code of the SARS-CoV2 ‘peak’ protein. “None of the vaccines acquired jointly by the European Union is the virus itself”, summarizes Ventura. “All of them lead, in one way or another, to the production of this ‘peak'”.
BASIC INVESTIGATION WAS ADVANCED
Why was the process so fast compared to normal vaccines? The reasons were several, according to the same expert. Right from the start, the public health emergency situation. “Certain phases took place as usual, but took less time”, he explains. The companies were already developing vaccines of the same type for SARS-CoV1 and MERS. “As the SARS-CoV1 pandemic has since disappeared, there is no longer any possibility of conducting clinical trials. There is no possibility of verifying whether the virus is effective in the environment. All this research was in the drawer.” This is the case with SARS-CoV, because in relation to MERS (still a problem in the Middle East today), the case is different. Pfizer and BioNTech also had a partner for a flu vaccine with this messenger RNA technology. “That is, basic research was already very advanced. This saved some years in advance “, says Ventura.
Another difference has to do with clinical trials. “They have four phases, three before approval and one last after. In phase 1, with lower numbers and a younger population. Phase 2 is dose selection. Then phase 3 begins, which in the case of vaccines should cover tens of thousands of volunteers, to be sure of the vaccine’s effectiveness. Normally, the phases are sequential. In the traditional process, each phase is expected to start before the next one. the next one started.
“When it was already known that it was safe to move to a larger number of individuals or to an older population, it went ahead. The phases have not been shorter, they are overlapping”, he says. “Nowadays, even in relation to Pfizer vaccines, which we are almost ready to have in our market, if all goes well, studies of phase 2 are still going on, at the same time as those of phase 3”.
NORMAL SIDE EFFECTS
Some unknowns remain. It is not known how long the protection lasts, how many times it will be necessary to get the vaccine, or if it only prevents those who take it from contracting the disease or also from spreading it to other people (the first signs of this seem positive, but it is too early for drawing conclusions).
The side effects, too, are still not entirely clear. Fátima Ventura notes that the tests are carried out in a controlled manner. “When we move to the global population, it is natural that side effects will appear. Those effects that only appear when millions are vaccinated. This is normal. It is nothing that does not happen with any medicine. When we read the leaflet that comes in the medicine boxes, we see the frequency of side effects indicated there: if they are common, rare, very rare … “.
“The effects mentioned so far in the studies are the usual ones: the tough guy on the arm, the discomfort on the body … In general, they are very similar to those of the flu”, he says. Even anaphylactic reactions, like those seen in two health professionals in the UK, are far from being unheard of, he says.
THE ROLLING REVIEW AND OTHER NEWS
Another relevant difference is that the industrial production of the vaccine was anticipated. “How can we say that, a few days after the European Commission approves the vaccines, we will already have them to give to people? This is because companies, at risk, started to produce even before being authorized. They achieved this with many support from governments and foundations that support research. There were incentives for companies to go as far as they could “, explains Ventura, giving the example of BioNtech, which will commercialize the Pfizer vaccine in Europe and has everything ready.
Also, the way the authorities are carrying out the assessment was different now. “We usually have more time. The normal process for approving a drug is 210 days in the European Union. For certain diseases that have no therapeutic alternative, that time can be shortened. It is already part of our legislation. It is called accelerated evaluation.” This time, at Europe level, a new mechanism was created. As the evaluation is made, the company submits this data to the agency and they are evaluated. “This is called ‘rolling review’, that is, continuous review”, says Ventura. “We are receiving the book in chapters, so to speak, and we evaluate each chapter. When we have all the chapters evaluated, the company formally submits the marketing authorization request. Usually,
PRECEDENTS IN CANCER TREATMENT
The Portuguese specialist also mentions, as another determining factor, the commitment of many teams, the reinforcement of evaluators that the agencies made. And he notes that the authorization will be conditional, as the clinical trials have not yet ended. “Companies are subject to a series of conditions, with deadlines to meet. The assessment therefore does not stop. If things are not going well, the authorization is withdrawn.”
If the new technique is much faster than the traditional one, there are objective reasons for this. In the traditional technique, “a virus had to be cultivated, cells were needed, etc. It took a long time. In the RNA technique, the first stage is the production of the mold from cells. But from then on, you don’t depend on the cells grow “, he explains.
From the moment the SARS-CoV2 genetic code was published, “it was very easy”, he adds. “The information was removed from the genetic code, the mold was made, and based on that, it was possible to produce a lot of messenger RNA. Otherwise, very small amounts are needed. A thousand times smaller than usual. With very little product , many people can be vaccinated. A quick technique, easy to industrialize, but of course, as it is new, it is more expensive than the others. ”
Covid-19 is not the first disease whose treatment uses these techniques. “Against the protein of a tumor, the approach is the same,” says Fátima Ventura. “Cancer drugs nowadays often have antibodies – so-called monoclonal antibodies. Immuno-oncology is one of the most effective ways to treat cancer. It is using our immune system to treat what is strange. viruses, whether they are cancer cells. ” The Moderna company, he recalls, was already developing this type of approach for a cancer vaccine.
THERE WERE NO SHORTCUTS
With the much greater openness of the scientific community that took place this year, including the appearance of pre-print platforms (ie, where study results can be shared almost instantly, without the months of waiting that the publication process in reputable scientific journals entails ), it could be nothing less than a real scientific revolution.
Even so, it was a terrible year. When we read that, two days after the publication of the genetic code of covid-19, Moderna’s vaccine was already invented, that all mortality happened after that, some raise ethical questions. The truth is that it could not have been otherwise. In science, there are indispensable safety criteria, and not having met them to the letter, in addition to other effects, could compromise the public’s confidence in approved treatments.
If the dramas of 2020, by giving enormous incentive to a new technique to fight diseases, lead to advances against scourges that have long afflicted humanity, the covid-19 may end up, at a certain level, a blessing for humanity . In any case, for now, there are reasons to be confident.
“Yes, we walked faster but we had conditions for that and there were no shortcuts”, sums up Ventura.