Paul Burton, the brilliant scientist of the Moderna laboratory: “Facing COVID we still have a long way to go”

When a disruptive event erupts globally, as happened with this pandemic due to the new coronavirus, the time to come will be dedicated to the management of that health chaos that will change the rules of the world forever.

More than 2 years have passed since the appearance of the SARS-COV-2 virus that causes the COVID-19 disease and despite the drama that figures exhibit around the globe, with 455 million infections and 6 million deaths, the same paradox emerges from the beginning: the vigor and prosperity of science and scientific work. Although with ups and downs, today there is a robust portfolio of vaccines available - from different platforms - and many to come; treatments that need to be consolidated but with advanced research underway. And the inequity of many countries with regard to access to vaccines and therapies remains in place.

The Moderna laboratory, of North American origin based in Massachusetts, in the United States, also went through important changes and ups and downs: from being a promising and small, almost boutique biotechnology hub, it became one of the key players during the COVID pandemic in just two years. Moderna was one of the researchers and developers of the most innovative finding against COVID - together with the competing binomial and pharma giant Pfizer-Biontech -: the genetically derived vaccine (Spikevax) based on the currently known messenger RNA (mRNA) platform that allowed a scientific advance of proportions against respiratory and other diseases.

The pandemic is still among us and this is corroborated by the rise in cases in several countries in Europe and Asia and why experts and regulators are pushing the world to move towards the fourth dose, “the near future will be to combine vaccines against influenza and COVID in a single injection, and once a year”, advanced convinced in exclusive dialogue with Infobae, Paul Burton from the host city of the Moderna laboratory, Cambridge, Massachusetts, United States. Dr. Burton is the medical director of Moderna and considered an eminence in infectology.

Doctor Burton, how do you analyze the crossing of that imaginary bridge that will take us from the pandemic to the endemic? How do you see that transition?

-Paul Burton: If they had asked me that question a month or 6 weeks ago, I would have told you that, at least in the Northern Hemisphere, we were going to enter a period of stability during spring and summer; and that the number of cases would decrease and that perhaps we would already be entering that endemic phase. The new BA.2 variant, this stealth subvariant of Ómicron, means to me that we are not really close to that yet. And that this transition or the eventual crossing of the bridge is still far away.

The fact that we have massive outbreaks of cases in Hong Kong, South Korea; or in Europe - the United Kingdom, France and Germany, among other countries - and after a wave of infection with Omicron that although vaccination increased; it makes me think that this is a virus that is capable of making very large changes or alterations in its function. Therefore, I think we still have a long way to go.

- Do you agree that expanding the base of people vaccinated against COVID is the most important health strategy to combat this pandemic?

- Absolutely. Moderna's COVID-19 vaccine, which integrates the so-called vaccines against the virus spike proteins or messenger RNA, is highly effective against the original strain of the virus and the Delta strain - the previous one dominant to Ómicron. It should be noted that Delta - is a very dangerous variant because it causes pneumonia, which is what hospitalizes and causes death to people. Moderna's vaccine is highly effective against that strain, so if vaccinated and boosted, it significantly reduces the risk of having a severe case of COVID.

However, there are many people around the world who have not yet been vaccinated or, if they have been vaccinated, have not received their booster vaccine. Part of the resolution of this pandemic really depends on vaccination, coupled with ongoing public health and social care efforts around the world: such as wearing masks, washing hands and some distancing. And also having transparent data on how cases and hospitalization go. If we don't have these tools, we won't be able to get ahead of or stop the virus. And in that sense, pediatric vaccination is undoubtedly one of the tools that will most help consolidate the trend of transforming the pandemic into endemic.

Moderna recently announced to the world the encouraging results of the Phase II study (KIDCOVE study) of its COVID-19 vaccine for children aged 6 months to 5 years.

The evidence gathered so far by the Massachusetts company, said that two 25-microgram doses of its COVID-19 vaccine for children aged 6 months to 5 years provided a similar immune response to two 100-microgram doses for adults aged 18 to 25. Both doses of the vaccine will be given to children 28 days apart.

-Going deeper into pediatric vaccines against COVID, what new data did this KIDCOVE study by Moderna yield? ; and Why do you think that even parents - mostly vaccinated - have doubts about vaccinating their children against COVID?

- About 7000 children between 6 months and 6 years of age participated in this study; 5000 received the vaccine, 2000 received a placebo. They received two injections of 25 mg with 4 weeks apart, which is a quarter of the dose that adults receive. We can be very calm about the safety of this vaccine. The rate of adverse events such as injection site pain, fever or general malaise was exactly as we would have expected, based on what we have seen in older children and adults as well.

Rates of high fever, over 40 degrees, were only observed in 0.2% of children and in other vaccines that are approved for this age group, we may have rates of 1%. When we looked at effectiveness, we measured antibody levels and today we know that those seen in young people aged 18 to 24 were around 1400 units. Fortunately, we found almost exactly the same levels of antibodies in these younger children: between 1400 and 1800 units.

This is great because we know that this level of antibodies will protect people - in this case babies and children - against normal COVID and against serious COVID illness that can lead to hospitalization and even death. When you combine these two things, safety and efficacy, it really shows that it is a good study, and that it is great news for children and their parents.

With regard to parents, the question is: what motivates parents to vaccinate their children? We know that, fortunately, COVID is less serious in children than in older people, but they still get it. And that will keep them out of school and will have an impact on the parents' working lives. COVID can be serious and prolonged COVID too, so we want to prevent these children from getting infected.

We must think about the fact that these younger children can act as a reservoir to continue spreading the infection to their elders. We have very good safety and efficacy data from this new vaccine 6 months to 5 years, it will prevent diseases, allow children to stay in school and prevent them from spreading the virus, these are the reasons parents should think about to vaccinate their youngest children when the vaccine is approved.

- Very interesting, Dr. Burton. If we could for a few minutes break out of the current pandemic state and look at the big picture of COVID vaccination, will the future be an annual double shot next to the flu vaccine? What will be the place of the COVID vaccine in the vaccination schedules?

- I think booster vaccines will probably be a part of life, especially during this phase of the pandemic. And as we reach the endemic phase, in order to keep it endemic, we will need more vaccines, we will need good levels of immunity.

I think BA.2 Ómicron has taught us that we need booster vaccines specifically for variants and at Moderna we are working on this: a vaccine against the Ómicron strain and one that combines the two booster vaccines that will also protect against Delta.

We are also studying booster vaccines in children, even for the youngest children. It seems reasonable to me that, if we need to continue to give regular booster shots to adults, we probably need to do the same for children. And as we can get more booster vaccines against specific variants, our hope is that we can reduce injections to once a year.

Now, the other hope we have, and we are working on it now, is to combine flu and COVID vaccines into one vaccine and give it to everyone once a year; dose and age range will have to be analyzed. This will prepare people for winter and protect them against these respiratory pathogens, this vaccine could be ready by the end of 2023.

Our hope would be that by the end of 2024 we will have a single vaccine against influenza, COVID and other respiratory viruses. These are viruses that kill and hospitalize many people around the world every year, so if we can put these vaccines together in one shot, I think the impact on public health will be very large. For all of this, the messenger RNA platform is incredible. This is a platform that if you know the target we are targeting, we put it on the lipid nanoparticles, and it becomes very predictable. It's a lot of work but the probability of success is very high.

- What will be the next goal for mRNA gene technology: what will happen to brain diseases, cardiovascular diseases, cancer?

-What follows are programs for all the diseases that you have mentioned. A year ago, we had 9 programs in development, now we have 39 programs in development, we have several vaccines in Phase III of development, so we are expanding all the time.

In addition to infectious diseases, we are looking at cardiovascular diseases, heart diseases, very rare diseases, metabolic diseases; something called propionic acidemia, is very rare but can be devastating. We have ongoing cancer studies, personalized vaccines, something like therapeutic programs.

And going back to infectious diseases, there we have a Phase III program on cytomegalovirus, a very common virus that causes hundreds of thousands of children to be born with birth defects, hearing loss or blindness. We have a program for this, it's a very complex protein, it's actually 6 different proteins, so it's very difficult to make a vaccine against something so complex, but in Moderna, with mRNA, we can join those 6 proteins into a single vaccine, that's the power of the platform.

Therefore, not only can we encompass diverse therapeutic areas, but we can enter areas that other normal therapeutic platforms simply cannot reach.

- The COVID pandemic has definitely changed the world. And it also changed the way science works, especially when scientists from all over the world began to research together, sharing information and results. Do you think this way of working will last?

- That's a great observation. I think this terrible pandemic taught us that if we work together, if we share information, and if we are transparent, we can come together and create high-quality therapies very quickly. It also taught us that we need to think a new way about how we approve drugs and vaccines, we need to be rigorous and put safety first. We now have a platform of nearly 500 million people who have received the COVID vaccine, and we really know everything there is to know about how it works when it is introduced into the human body.

This means that while we think about another disease - such as the flu or cancer - we can have a new, accelerated way of bringing these therapies to people and getting their approval. I would never have imagined a world in which we would be treating five hundred million people in a year. The amount of evidence and information that was obtained in this way has no background.

Burton has a doctorate in medicine from the University of London, his native country. His specialized training is in cardiothoracic surgery. He is a PhD in cardiovascular cellular and molecular biology from Imperial College London and a member of the American College of Cardiology, among others.

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