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TRANSFORMATION | 03.11.2020

Mariano Esteban: “We need to have confidence in the scientific community; we’re the ones who have the greatest responsibility” 

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For Science and Innovation Week 2020, we’re back with Mariano Esteban, Researcher at the CSIC (Consejo Superior de Investigaciones Científicas — the Spanish National Research Council), Head of the Poxvirus and Vaccines Group at the CNB (Centro Nacional de Biotecnología — Spanish National Center for Biotechnology) and member of the WHO scientific committee. We’re following up on his vaccine project to combat COVID-19 and the lessons learned since our previous interview when the pandemic was declared. Esteban is emphatic: we need to understand that the virus will continue to be a reality and we need to avoid infection, because the cruelty of this pandemic is in how quickly it can be spread by those who are asymptomatic. As someone who has dedicated his life to fighting the viruses that have plagued the world, his thoughts revolve around unity, confidence in the scientific community and gratitude for the support that companies like MAPFRE—the first to commit, with a donation of 5 million euros to support the institution—provide to the CSIC.

Question: Your vaccine was successful in animal immunogenicity trials and you’re starting clinical trials. What’s the current status of your project?

We already filed a patent for the MVA-CoV2-S vaccine candidate that we developed. This vaccine candidate is being produced by a Galician company and clinical batches are being manufactured. We’re also working on the dossier for submission to the Spanish Agency of Medicines and the European Medicines Agency, so we’re pretty far along in the process. We also submitted a scientific article and recently received feedback, which was quite positive on the development of the vaccine. We also joined forces with Leuven University for a hamster trial and with the Biomedical Primate Research Center in the Netherlands. We’re planning to start Phase 1 and Phase 2 clinical trials, with about 100 and 500 volunteers respectively. The trials will be conducted around the same time, in early 2021. We’re also producing other alternative vaccine candidates, in case resistance develops or the current vaccines do not provide adequate protection. As second-generation vaccines, these would have a wider spectrum of action and could be cross-reactive against other coronaviruses.

In addition, we read that your colleague Luis Enjuanes, along with his team, is developing “the most complex vaccine in the world,” the only one that uses a genetic modification of the virus.

Yes, and they’re making great progress. Luis Enjuanes, a global coronavirus expert, and his team are developing another vaccine candidate based on the coronavirus genome sequence in the form of a replicon, in which the virulent parts are removed. As can be expected, it’s taking longer because it’s a complicated process. They will have it ready by the end of 2021, and they’re confident that it will produce a broader and more effective immune response.

At what point will you be able to say to yourselves: we achieved what we set out to do as scientists?

When we prove that the vaccine is safe and highly effective. That’s the goal.

Can you guarantee that there will be safe vaccine, wherever it comes from, by the end of 2021?

Yes, definitely. Knowing the regulatory agencies, namely the EMA in Europe and the FDA in the United States, the researchers behind some of these vaccines and the multinational commitments to not release any vaccine that isn’t completely safe for the population, I’m not worried about that — I’m absolutely sure that it will happen. As with any drug, the vaccine may have some unforeseen side effects, but that’s normal. 

What can the public expect then?

Well, I was thinking about this when I got a flu shot two days ago. I was so calm, I got the shot and walked out thinking about what it would have been like if it had been the coronavirus vaccine, an event to remember. We don’t realize how extremely valuable vaccines are for humanity in terms of health. We’re all looking forward to that moment, and it will come.

And that moment will not have a nationality or a caveat…

Not at all. I asked the nurse which one it was, where it came from — but out of scientific curiosity! And she told me, of course, here it is [shows the label]. Nobody worries about where vaccines come from, the general concept is you go, get it and that’s it. What people care about is knowing that they’re going to be protected.

 

“We don’t realize how extremely valuable vaccines are for humanity in terms of health”.

The CSIC just issued recommendations on ventilation to reduce the risk in certain spaces. How should the public interpret these changes, for example is the assumption now that the virus is transmitted by air? 

We’re learning a lot from this infection. Remember that it first appeared in China in December [2019] and the first cases in Spain were at the end of January. We didn’t think there would be widespread infection. As with SARS CoV and MERS, we’ve been learning a lot from knowledge of the virus and how it spreads among the population. And we’re gradually taking measures to provide physical barriers: trying to control and prevent infection by wearing masks, social distancing, washing our hands, ensuring better air circulation and especially sticking with a small bubble of people from our social circle. If there are infections, we should take action. We can be more relaxed and calm when there aren’t. The virus is teaching us to lockdown and try to protect ourselves as much as possible. It’s true that the virus itself is tiny and can be transmitted through very small particles such as aerosols, but to become infected, you need to contract a sufficient dose — the body can quickly eliminate smaller quantities. 

CNB image: Mariano Esteban, sixth from the left, with his team.

Looking ahead to the upcoming holidays in much of the world, do you recommend anything special? What will we see in the near future?

It would be great to celebrate the holidays like we always do, but that’s not going to happen. This is going to continue and we’re going to quarantine. According to all the forecasts, there will be a strict lockdown. We’re not going to have the virus under control, nor will we have achieved very low or zero levels of infection by then, although we will have flattened the curve quite a bit. I believe we will continue along this path until well into 2021.

How has your view of the SARS CoV-2 virus changed in the past few months? Has anything surprised you?

Normally viruses appear and disappear. But this one is persistent. It keeps circulating because it has the “added advantage” of largely asymptomatic transmission, meaning that it is often spread without being noticed for days or a week. Only when a person is feverish, achy, congested… that’s what makes this virus so cruel: it’s very difficult to eliminate without a vaccine, which is how we’ll eventually do it. If not, we’re going to be jumping all over the place. We thought that France, the United Kingdom, Italy and the Netherlands had it under control… and then there’s another outbreak, another wave. That’s because of this ability to go unnoticed, without people taking precautions, spreading the infection. When people get infected in a large population, we don’t notice. We only notice it and isolate ourselves when the infection shows symptoms, or if someone goes to the hospital once it’s already affected the lungs and caused respiratory problems.

What’s happening in Spain? 

Our unique trait, our inability to agree. Because the scientific community is a homogeneous group. You present something, you propose a hypothesis or you present some results and they’re clear. Outside, there’s confusion. Society wants us all to agree and act in unison, to stand together, but what happens is that everyone has an opinion, everyone thinks that what one person says opposes their own view and has to be refuted. Our heterogeneous nature in this country, where populations have mixed for centuries, means that we’ve developed a very interesting population, which is highly qualified to take on anything, but we can’t agree on anything. When we could be moving quickly, we sit idle.

What is “confidence” for a scientist with your level of responsibility?

I have confidence in the scientific community. I have been working in this field for many years and everything is always based on real, proven and confirmed facts. Everything has to be confirmed with facts; that is scientific argument. I’m on an advisory committee that issues carefully crafted reports available to anyone on the ministry’s website. But then there’s a tweet, and then a response, and people pay more attention to that than evaluations or assessments by very qualified people, because they’re too long. What people want is three or four lines. We’re moving so fast, without the rigor and quality required in professional sectors. That’s where we fail. There are so many hoaxes and, unfortunately, that confuses the public.

What message about our current situation do you think is important to emphasize?

We have to take responsibility. There are very useful guidelines from the Authorities that we need to follow to avoid chaos. At the international level, I am also an advisor for the WHO. We’re meeting in the next few days about how protected the world is against the smallpox virus, and with the organization’s support, we continue to work on all types of diseases to prevent outbreaks. We are always vigilant. Like when conducting an experiment, mistakes have naturally been made in this pandemic, but it’s a matter of learning from them and making changes. I think the message is that we have to follow the recommendations, comply with them and try to prevent the pandemic from spreading. Above all, we need to be very aware that the virus is all around us and we have to do our best to avoid becoming infected. We also need to have confidence in the scientific community, since we’re the ones who have the greatest responsibility to overcome the virus using the tools available to us: rapid diagnostic methods, therapeutic measures, developing new drugs and therapies to manage the disease, and developing vaccines. This is underway and we’re progressing quickly. We need to be patient, but stay alert at all times.

How is support from businesses used, how important is it and why? How are the CSIC projects supported by businesses progressing?

The institution is helping a lot, thanks to contributions like the one from MAPFRE. The CSIC is in a very good position and is boosting research related to this pandemic, so that we researchers can try to use our knowledge to fight it at all levels: with faster diagnostic methods, therapeutic methods, vaccines, strategies to treat those who are infected… Thanks to this support, new rapid diagnostic procedures have been developed, antiviral drugs are being identified and several SARS-CoV-2 vaccine prototypes are being developed. The institution had limited resources, used by researchers for projects or the institution’s budgets. I think this is the first time in Spain that civil society and business have stepped forward to help the institution in the form of donations, which is commendable. I would like to see this patronage become standard practice, as is the case in other countries (the United Kingdom, United States and others). MAPFRE was a catalyst for this — the first to approach the CSIC.