COVID-19. Can the Oxford vaccine mistake be corrected? “It is through error that the most fantastic discoveries emerge”

After all, can an apparent error turn out to be a completely right solution? Virologist Pedro Simas explains to Expresso what makes him believe so. The researcher from the Institute of Molecular Medicine also clarifies what differentiates this vaccine – with an approach closer to the Russian Sputnik V – from the cold options presented by the main competitors: “Pfizer and Moderna’s vaccines have an RNA technology base, while AstraZeneca uses a recombinant virus “.

The vaccine developed by AstraZeneca and the University of Oxford is questioned, as the 90% efficacy obtained, in the best cases, was only recorded in a group of 2,700 volunteers, who were given half a dose instead of the two. , among a universe of 24 thousand people who participated in clinical trials. Does this affect the credibility of what has been announced?
It is said in [revista científica] “Nature” that detected, in a large group of volunteers, reactions to the vaccine, such as fever and malaise, which are normal – and are normal because the vaccine is a living being. Upon investigation, it was found that a lower dose had been administered. This happens sometimes in science. I think this mistake was neither deliberate nor hidden.

Do you think, then, that this is not an advertising strategy in a possible trade war between pharmaceutical companies?
Nor is it about believing or not believing. I do not subscribe to any conspiracy theory. I have read what I think is trustworthy. And, as a scientist, I know these mistakes happen. Science is transparent. I never imagined that a company like AstraZeneca would compromise a history and reputation of so many years, as well as compromise an operation that cost billions, because of something like that. I do not believe it. What arises now is a small administrative problem, which has to do with the protocol defined by the FDA to approve emergency use of the vaccine.

And what is this administrative problem?
These studies are very well designed and marked by regulatory authorities. If the study entered with certain premises, if there is any change afterwards, the results must be equated. But, from a scientific point of view, it is quite common. There are many discoveries that are made just because people were wrong.

Can you give an example?
Penicillin was discovered by accident. Alexander Fleming noted that there were fungi that prevented the growth of bacteria next to them. Was this how the first antibiotic was discovered and did you see the impact it had on the history of medicine? This is to say that it is absolutely normal and fortunately it is. The reason why biological nature is so robust has to do precisely with the fact that there is a great deal of redundancy that comes from diversity. This is where Darwinian evolution works. If we take a computer and change 20% of the software, it will stop working. But if we take our genome and change 20% of the genetic code, we probably don’t notice any difference. It is through error that the most fantastic discoveries emerge.

This vaccine – compared to Pfizer and Moderna’s competitors which achieve an average efficacy of 95% – has a higher success rate, between 62% and 90%. Is it normal to have such a large discrepancy in efficacy that the vaccine can have in different groups?
This, honestly, also gives me more confidence, because the results were obtained based on different dosages and, as a result, there is a different immune response. It’s normal. It should also be noted that they are different vaccines. Pfizer and Moderna vaccines have a technological base of RNA, while AstraZeneca uses a recombinant virus.

Fighting fire with fire?
What this vaccine does is use a genetically modified adenovirus in order not to be harmful; that is, it is a virus that is unable to spread to the person being vaccinated. It serves only as a vehicle, a transport to produce peak proteins in cells. In short: an adenovirus is administered with the coronavirus spike protein gene. This technique is similar to the Russian Sputnik V vaccine, which uses two adenoviruses, which is very clever. This diversity of approaches will be very useful in covering the entire population and reaching all cases.

What are the benefits of this approach in vaccine development?
AstraZeneca’s vaccine is cheaper to produce and has committed to selling it at cost during the pandemic, and its storage is easier.

And how do you explain that it can be much easier to maintain and, at the same time, much cheaper?
RNA is extremely sensitive and must be stored at -80º, in Pfizer’s case, so that there are no degraded enzymes, although Moderna says it can be stored at -4º for a month and at -20º for six months. An adenovirus, such as the one used by the AstraZeneca vaccine, can adapt to the environment, it can last hours or a day on a surface. A modified virus is always more robust than RNA, because viruses do just that: to be resistant. Therefore, all the technology to produce and store a recombinant virus is much simpler and much less expensive. Working with RNA is a much more delicate process.

There is, however, a common point between the different vaccines tested: we always talk about two doses. How do they both work?
If we give too much antigen at once, it can be depleted and it can be harmful. But more than a quantitative problem, it is the need for the shots to be spaced over time. The first dose serves to activate the immune system and, as a result of this activation, an immunological memory is produced. The second dose serves to activate this memory and make it more specific, increasing the extent of the immune response. That’s why vaccines are given over time, with an interval of three to four weeks. More than talking about two doses, we are talking about two vaccinations.