The CSIC's most advanced vaccine against the coronavirus has slowed down on the road. The end has been disconcerting for many: although the previous phases have demonstrated the effectiveness and safety of the prototype in animals, the public body refuses to test the vaccine with humans. Mariano Esteban, the retired virologist who has led the process from the National Center for Biotechnology, reveals in this interview that the road has been long and difficult due to the lack of scientific infrastructure and companies that produce the vaccine in the face of the speed of large pharmaceuticals.
Esteban defends, contrary to what the Spanish Medicines Agency (AEMPS) has assured, that they did present the clarifications they were asked to carry out the trial with humans, he talks about how the "market" of vaccines already influences decisions available and is committed to continuing research to provide something new, such as longer-lasting immunity.
Why have they given up doing the test?
Some time ago we had submitted the request to the Spanish Medicines Agency (AEMPS) and now most people are vaccinated. What is more appropriate is to think of the vaccine as a booster dose or to optimize that it targets the different variants. We pursue the universal vaccine and the one that grants lasting immunity.
What clarifications did the AEMPS ask you for? Why couldn't it go on?
He asked us questions and we answered. What happens is that time has passed and we have thought that the approach should go to update the situation of the vaccines and to think to what extent we can contribute to enhancing the degree of immunity.
But what specific aspects did they ask you to clarify?
They are confidential. We responded in September and the CSIC and Biofabri – a Galician company in charge of manufacturing the batches of vaccines for human trials – have considered that it is not appropriate and the best thing is to position ourselves in the situation in which we find ourselves today.
So the decision has to do with being late in some way?
In April 2020, the Minister of Science, Pedro Duque, came and said that we had the vaccine. We had a vaccine candidate like the others, but we couldn't develop the vaccine quickly because we didn't have the right infrastructure to proceed with trials. For example, we had no animal models and we had to stand in line. The trial with macaques was done in the Netherlands. We had two level III biological safety laboratories that had to be conditioned to carry out the experiments. Another problem is that there were no companies that could produce a vaccine for human use. We had to push and Spain has entered that development. That is important as a country.
The lack of infrastructure slowed them down, you mean.
Yes effectively. But now we have teams. The danger that we all run is that there is an abandonment of all this. That after the pandemic tell us: gentlemen, very grateful, but see you later. Great care must be taken to maintain research centers.
Are you going to conduct the trial with people in other countries?
It's open. The important part is to develop the research and transfer it to the productive sector. We are open to talk with different actors both inside and outside of Spain. The vials are produced and we have shown that the behavior of the vaccine is very good. And so it is posted. We are also open to using the vaccine in continents where it is more difficult to access other vaccines. It is important to have several, we cannot place the bet on only one.
Before, I commented that they had considered using the vaccine as a booster.
We have done a lot of work on the combination of vaccines and we are in a position to use it in booster doses, or as a single vaccine for primary vaccination.
Do regulatory agencies now act the same as at the beginning of the pandemic? His research colleague, Juan García Arriaza, said in an interview that they have become more demanding.
Completely. At first, the vaccine had to be 50% effective to go to the clinical phase. It was the first requirement, the one they put on us. Like all things, they changed as data became available and it was seen that some conferred protection that could exceed 90%. So these ranges have been increased: now they ask you for practically 100% efficiency of neutralizing antibody production. You have to prove that your drug is equal to or superior to those on the market.
Is there some competition between vaccines behind this decision not to continue with the clinical trial?
Yes, logically. I understand that you bet on certain vaccines. This does not mean that research continues so that they can complement or be used in other circumstances and that is part of the science of any country. We are seeing that RNA vaccines offer protection but decline, especially against new variants. Science continues, we try to ask questions and answer the durability of the immune response, the control of aspects of the disease caused by the virus, which genes are activated, what happens with the post-COVID effects...
Is it an economic issue?
I don't go there anymore. I only look for the benefit for science. You can decide to bet on this and that, but this changes over time. Other factors intervene that are not only scientific.
Looking back, how do you rate the whole process?
I am very positive for everything that has been achieved in this period of time. Spain has opened a field of action to protect the country. When we started, we found ourselves with a series of difficulties that have been solved. That is what we have to stay. We have vaccines and they are good: ours, and also those of my colleagues Enjuanes and Larraga [los científicos que están trabajando en otros prototipos de vacunas en el CSIC] . We have vaccine candidates that complement each other and that gives us more security.
Can you compete with big pharmaceuticals?
Pfizer is a multinational with billions, but we compete for publications. Ours are more complete, we are in the front line and we have to feel proud. We have mobilized the international sector. At the level of development, we have no equal: Spanish companies cannot compete with Pfizer but they can produce enough vaccines to meet the country's demand.
Was the process expected to be like this?
We were doing very well, but it was an obstacle course. The vaccine has a path that can be important and that is the Spanish contribution. We are as good or better than other countries, but we have to believe it. Young people are extraordinary but we do not give them facilities. It is the pending subject, to see if the science law increases the morale of young people so that they work in Spain.
Although it is positive, it is difficult to understand that if the vaccine has been successfully tested on animals, it should not be tested on humans. Let the process be cut.
I understand, yes. But the prototype is still there to see if the trial proceeds. I hope so.
Do you have any hope that it will eventually materialize into a usable vaccine?
I hope so, I have full confidence that it can be used anywhere. The important thing is that it is there. I don't get into a 'is this vaccine better or worse' race. It's good, period.
The minister assured that what has happened is normal in science, do you still have a feeling of failure?
For the love of God, nothing to fail. The important thing is that science continues to advance and what we have contributed must be published. Without publishing it, there is no place. It has to be verified by the scientific community and we have fulfilled all the requirements: we have demonstrated the behavior of our vaccine with three animal models. And the study says in the end that this predisposes him to the preclinical use of the vaccine. We have seen "goodbye to the vaccine" headlines, but nothing goodbye. We keep trying to contribute.