The physician, who rose as an authoritative voice during the worst stage of the pandemic, researched the respiratory syncytial virus for more than 20 years and has just finished a study on a new vaccine. In an interview with Infobae, he talked about his scientific career and gave details of his research.
Fernando Polack remembers one of his childhood cartoons and smiles: the Roadrunner. The Argentine physician who played a central role during the worst stage of the coronavirus pandemic believes he has put a bow on his career as a scientific researcher. The same team that tested the world's first vaccine against COVID (Pfizer-BoiNTech) at the Military Hospital has just concluded a study of a vaccine against a virus that Polack knows very well: the respiratory syncytial virus (RSV), one of the agents of bronchiolitis.
Respiratory syncytial was Polack's research focus since the late 1990s. In 2020, the pediatrician led the COVID-19 vaccine study. But in 2022, in the testing of Pfizer's vaccine against RSV -finalized a few days ago- he accompanied Gonzalo Pérez Marc, who intervened as principal investigator, Romina Libster and Silvina Coviello and more than 700 health professionals and technical and logistic support of the studies.
A few days ago Pfizer reported that the vaccine efficacy is 85.7%. This means that, when approved, there will be a vaccine against RSV. After more than 20 years of research on RSV, Polack and his team recruited 8,000 volunteers in Argentina and thus contributed to the study called Renoir, which was carried out in several countries.
The respiratory syncytial virus vaccine trial has something special for Polack. He has been researching this virus since 1999. It was back then, when he was living in the United States, that he stopped studying the measles virus and started with respiratory syncytial virus. He tried to explain why a vaccine against RSV applied in 1967 had failed and had caused deaths. He got right into that research, got it wrong, reformulated his hypothesis and finally succeeded in determining what had gone wrong 55 years ago. From that moment on, Polack worked to define safety criteria for new vaccines and collaborated to find a vaccine that would protect against respiratory syncytial.
In 2003 he had returned to Argentina and devoted himself to investigating how the virus affects children born in the poorest sectors. For his work on RSV, in 2006 the Pediatric Society of the USA had awarded him the prize for the best young researcher. Four years later he was chosen as the best pediatric researcher.
His respiratory syncytial virus research team in Argentina became a central player in respiratory syncytial virus research in the world. They received awards and published an enormous amount of information.
In the midst of the pandemic, in addition to leading the testing of the vaccine, they conducted the first study on the usefulness of plasma from recovered patients to prevent severe infection with COVID-19. Later, other studies were carried out in the United States that corroborated what Polack and his team had determined a year earlier.
In 2022, that research race seems to have reached the finish line. The aim of the trial commissioned by Pfizer was to find a vaccine against a little-known virus that has serious consequences in two sectors of the population: newborns and the over-60s.
The researcher's team, which has been studying respiratory diseases for more than 20 years, tested the first vaccine that proved highly effective against RSV. " It's as if Wile E. Coyote was able to catch the Roadrunner after all this time," says Polack, smiling.
After the vaccine's efficacy level became known, Polack spoke to Infobae.
-Respiratory syncytial virus is linked to COVID?No, but it works very much like COVID and that's why I was called in to head up Pfizer's coronavirus vaccine program. I was part of the scientific advisors for respiratory syncytial vaccine development in the United States and in organizations in the European Union, and that's why I was called in when the pandemic started. Many pharmaceutical companies and international health agencies needed experts to understand a virus that had never existed before, so there were no experts in the world. So many of them looked for those of us who knew about respiratory syncytial disease.
-So that's how your relationship with COVID-19 began?Yes. That's why I could think COVID easier, because the germ was so similar to syncytial in how it behaved. And I had been doing research on respiratory syncytial for more than 20 years. I knew that plasma with antibodies was only going to work in that way, because I knew how antibodies against respiratory syncytial work. And I understood that the vaccine was only going to work in certain ways, because I knew how they didn't work against respiratory syncytial.
-Can you explain what causes RSV, the virus you have been pursuing in your research?
-It is the main cause of hospitalization in children under one year of age in Argentina and in the world. And if you go to a sanatorium in the Federal Capital or a hospital in the suburban area between the end of May and August, 70% of the children hospitalized, that is to say, 7 out of 10 have respiratory syncytial disease.
-What is the diagnosis given to the mothers when they arrive at the hospital?
-In principle, RSV is the agent of bronchiolitis. Bronchiolitis is a disease that affects about 20% of children and hospitalizes between 1 and 3%.
-What are the effects of respiratory syncytial?
-Respiratory syncytial in Argentina and the rest of the world is the main cause of death in infants between one month and one year of age.
-What happens during the first month of life?
-In the first month of life the risks are different: what kills are perinatological problems. This shows the quality of obstetric and neonatal care in a country. If pregnant women are monitored, childbirth is controlled and there are tools for safe childbirth, this is reflected in the number of children who survive these stages. In countries with more resources, there is very low mortality, countries with medium resources have intermediate mortality, and in low-resource countries women usually have uncontrolled deliveries at home and even have sidereal mortalities.
-And after that stage, what happens?
-Once the first month has passed, one variable that becomes important for measuring the quality of public health care is mortality in the home. Countries with more economic resources have almost no deaths at home, except for exceptional deaths associated with sudden death. Countries with deficient structures, such as Latin American countries including ours, have deaths at home in the most vulnerable areas which they call "sudden deaths" because they do not investigate them. Then they take the name used by developed countries to describe the cause of death they typically suffer there. For example, the United States has 4 million births per year and approximately 50 children die from respiratory syncytial in one year.
For his work on respiratory syncytial virus, in 2006 the American Pediatric Society awarded him the Best Young Investigator Award.
-What happens in countries like ours?
-Argentina has 600,000 births of which probably about 300-600 children die from respiratory syncytial. Fifty times more than in the United States, it is difficult to know exactly the difference. The highest mortality occurs in poor areas of several provinces and in some sectors of the suburbs. There, about three children out of every 100 are hospitalized for respiratory syncytial bronchiolitis and one out of every 2,000 dies. All this work to better understand what was happening in Argentina was carried out during more than a decade with the support of the National Institute of Health of the United States, the Molecular Research Council of Great Britain, the Conicet, and the Gates Foundation.
-Is the mortality rate the same everywhere?
-No. In areas such as the City of Buenos Aires, the person who dies from respiratory syncytial is a child who has many previous health problems. For example, he has growth failure in the lungs, serious heart problems, or previous severe damage to the brain. This is the child who dies in the United States, in Western Europe and who dies in the Capital City or in cities such as Córdoba or Mendoza.
-And in less favored places?
-The child who dies of respiratory syncytial disease in the poorest areas of the different continents is a child who is mostly healthy and who dies of poverty. That child dies in two ways: he dies in the hospital because there is no infrastructure or equipment to support him and then he gets over-infected with another bug that is going around, or the hospital does not have the appropriate respirator or equipment. That is the cause of about 50% of the deaths. The other half of the children die in the home of a needy family, which does not even have enough support from the State to save that child (because that child would not die in the Capital) and has no family record of the seriousness of the situation. Many mothers who raise their children alone suffer there, people live under attack due to environmental pollution problems, housing structure problems are serious, access to health care outside daylight hours is a chimera, and in winter there is a damp cold that cannot be felt in a downtown apartment. So these children die "silent deaths" at home.
RSV is the leading cause of hospitalization in children under one year of age in Argentina and worldwide (IStock).
-Was that what you investigated?
-What we did for more than 20 years is to investigate prevention strategies to mitigate those tragedies, to understand those deaths both in hospitals and in populations in the south of Buenos Aires suburbs that nobody had suspected to be associated with syncytial disease, neither here nor anywhere else in the world. This is by no means unique to Argentina, although that does not make it any better.
-What did the work in those places consist of?
-Among other things, we did studies that mapped the biological and social causes of disease and death in the most vulnerable children, we trained provincial staff in how to perform minimally invasive autopsies to find those previously ignored causes, we mapped the diet of mothers to see what interventions could lower the risks for their babies, we worked with premature children, and so many other things.
-What did you focus on?
-For example, we worked a lot on breastfeeding, which is an enormous protective factor against respiratory syncytial disease. A very interesting and revealing finding we made years ago working at the Garrahan Hospital and the Sardá Maternity Hospital was that breastfeeding protects premature women better against respiratory syncytial disease than premature men.
-Why?
-A woman knows how to do something with the milk she absorbs during lactation that a man is not so good at deciphering. Everyone needs lactation, it's just that women use it better. We must think about this from an evolutionary point of view, how we are still going around the world millions of years after the first prototype of us appeared. According to the Darwinian logic of becoming stronger in the face of the challenges we are facing, what cannot happen, if we humans want to continue to be around, is that most women disappear. Because 50 men and one woman lead to war, while one man and 50 women can keep us going. So, evolutionarily, nature protects the female better than the male, boosting lung growth and development during lactation.
"So after many years of working with us on the effects of the virus in the field, the Gates Foundation told us it was important that we develop the ability to test vaccines," Polack said (REUTERS/Lukas Barth).
-For respiratory viruses?
-Fundamentally for respiratory viruses. For the rest of the problems, I don't know the evidence to suggest that benefits also differ by sex. I simply don't know enough. But in respiratory, syncytial accounts for seven out of ten serious infections each winter. It's owned the winters, so far....
-And you applied that here?
-We then worked for five years in Chaco and Corrientes with a very ambitious program, since there were many mothers who could not or did not want to breastfeed. We wanted to define whether a premature baby who did not breastfeed could benefit from receiving milk from a donor mother. And we set up a huge randomized study (now everybody understands this word) to test it against what those children usually took, which was formula milk. Then, because we needed a lot of donor mothers to donate milk to feed more than one child, we set up a huge program supported by a private foundation in the United States to promote breastfeeding and to get donors. Unexpectedly, we brought lactation up to over 90%. Then, we ran out of babies who were not breastfeeding, so we could not do the study.
-That is, they were not able to do the study but the mothers breastfed.
-Luckily the kids were more protected, but we couldn't conclude the study. It was a victory on the unexpected side. Some time later the same thing happened with a similar project by Italian researchers.
-What else did you do?
-We set up a huge program in the conurbation with the Gates Foundation that worked on mapping and lowering mortality in the home. In parallel, we worked on severe disease and respiratory syncytial mortality in hospitals. There, through a series of findings, we ended up studying the maternal diet of pregnant women. And we ran head-on into the effects of the Paleolithic diet: the more sugar, flour and starches pregnant women ate, the more risk their newborns had of having serious problems with the virus. Since the Paleolithic diet was not yet in vogue, it took us a while to understand what we were seeing. At that time, we put the chips on fatty or high-protein diets, but the effect was clearly on carbohydrates. That's the beauty of science: you almost always start out wrong. Today, everyone knows that sugar is a nasty bug.
"The vaccine that we have just finished testing reached 85.7% efficacy in older adults, a ridiculous number given the progress made in recent years," Polack told Infobae (Maximiliano Luna).
-Did you discover anything else in the research in Argentina?
-We also discovered that there was a gene which, when mutated, considerably increased the severity of respiratory syncytial disease in the middle class population of the Federal Capital. On the contrary, for children from the most vulnerable sectors of the suburbs, having that mutated gene protected them against the same disease. This study allowed me, for the first time, to obtain funds to work in Argentina.
-How do you explain it?
That's called gene-environment interaction. A fascinating finding. It all depends on the amount of bacteria living in your environment. When you live in a very clean environment, that mutated gene (which was born to protect us from excess infectious agents) goes crazy in the absence of signals and triggers allergy-like responses. So those kids do worse with respiratory syncytial. When you live in an environment with more bacterial load, either because you live in overcrowded conditions or you don't have sewers, you are exposed to more bacterial load and that mutation, just as it did in the Paleolithic era with everybody, protects you. That was one of the first works we did with the Infant Foundation 20 years ago. But it was a very long research; it took a decade to figure out what was going on.
-When did the Gates Foundation contact you about testing vaccines?
-I had worked on Gates Foundation measles programs in Africa in the 1990s at Johns Hopkins and knew people in the organization's respiratory programs. At one point, about 15 years ago, the Foundation began to focus more on respiratory syncytial virus. It's hard to gauge how phenomenal the Gates Foundation has been in improving or solving problems in the developing world. Those of us who were passionately discussing mouse responses to viruses in the lab in the 1990s were propelled into the field to look for concrete solutions for kids. And that, to a large extent, was done by the Gates Foundation. While there was some initial resistance to the emergence of such a powerful force pushing many scientists where they didn't anticipate going, there's no doubt that the effect has been sensational. So after many years of working with us on the effects of the virus in the field, like many other sponsors, they told us that it was important for us to develop the capability to test vaccines. They saw that the respiratory syncytial vaccines that were coming were going to need a lot of testing sites, and they wanted hard data from the developing world because it was in those populations that they wanted to get protection. We knew a lot about the immunity needed to protect, about the disease, and there we learned as a team how to put together the best possible vaccine site.
-Did they know how to do it?
-Vaccine testing is a different business, it is another story, another thing, so we started to set up a vaccine testing structure.
Argentina has 600,000 births of which probably 300-600 children die of respiratory syncytial disease (Getty).
-When was that?
-I don't remember exactly, maybe after we helped define the pediatric influenza vaccination criteria for the whole world with a very famous paper that Romina Libster led. That year, 2010, we also did a very important paper explaining why middle-aged adults were dying during flu pandemics, which is very, very scary. It must have been then that the Gates Foundation sent a team of specialists to Buenos Aires to advise us. When the visit was over, and I was taking the director of the group to the hotel, the guy told me 'what you are doing is wonderful, but you have no idea about testing Phase III vaccines'. That's when we realized that we had a lot to learn. And Romina Libster went to the United States to the university where I was Full Professor of Pediatrics, and spent five years in the vaccine unit of the National Institute of Health in the United States. We changed the type of work we had been doing with Gonzalo Pérez Marc, who already had experience in clinical trials and an immense talent for putting together the most unlikely structures. Silvina Coviello, who is a biochemist and was with me at the Infant Foundation from day one, began to work on the protection of rights and information of the subjects involved in the studies. And so we set up the first vaccine testing program. That grew with people working with me and Gonzalo, expanded with hundreds of volunteer workers during the plasma project, and reached more than 1,000 people employed in the pandemic during COVID testing. The expansion was such that, for example, it enabled the construction of new areas at the Military Hospital which has been an excellent "coworker". We modified the way vaccines are studied so that they reach people well and earlier.
-A decade before COVID-19
-Romina said we had to prepare for a pandemic and I laughed. It sounded absurd to me. COVID was a long way off when we put together the first program to test a vaccine for pregnant women against respiratory syncytial. To be approved by the Food and Drug Administration (FDA), it had to have about 40% efficacy. The vaccine we have now finished testing achieved 85.7% efficacy in older adults, a ridiculous number given the advances made in recent years.
-As happened with some COVID-19 vaccines.
-Of course. That didn't happen before. That vaccine against respiratory syncytial reached 39% efficacy, and it was not enough. But in Argentina and South Africa the efficacy was significantly higher. And it had several unexpected side benefits. In countries where there were more vulnerable conditions, the vaccine worked very well. In the central countries it worked poorly and that lowered the average efficacy.
-Then, the situation in the central countries prevented the vaccine from being obtained.
-An important issue arises here. As it is very difficult for countries with many political ups and downs and few resources to make individual sanitary decisions based on their own data, decisions are often imported from the central countries and some products never arrive. This is a problem common to all of Latin America, some sectors of Asia and Africa. In South America, having a Mercosur of experts to be able to evaluate complex decisions - which is nothing other than learning the lesson of the European Union - is imperative.
-There is also a search for profit maximization by pharmaceutical companies.
-It happens that the central markets are much more powerful and if the vaccine is not going to be sold in the United States, Europe and Japan, the attraction is less. Hence the enormous value of the World Health Organization, which strives to bring products to countries that obviously need them.
-How was the beginning of the study of the respiratory syncytial vaccine?
-We finished working on that vaccine, which had not reached the desired efficacy, and we were about to test the Pfizer vaccine against respiratory syncytial. And then the pandemic hit. COVID got in the way. We stopped and resumed testing against syncytial this year.
Polack's team is currently testing the RSV vaccine in pregnant women (Photo: CDMX).
-Why was it initially tested in people over 60?
-These vaccines are usually tested in both groups, children (in this case in pregnant women who pass antibodies through the placenta to their babies) and in older adults. Here, in addition to the obvious imperative need to protect newborns, it is necessary to protect those over 60 when they need to avoid a serious disease. This represents an opportunity to reach a great number of people with vaccines, since life expectancy is getting longer and longer. So it is a population that all developments are paying a lot of attention to.
-You have already explained how it affects children, how does it affect the elderly?
-Respiratory syncytial infection significantly increases the risk of going to intensive care when you are an elderly person, increases the risk of having pneumonia, probably triggers asthmatic crises and also increases the risk of having heart attacks. If you had a respiratory syncytial infection, during the week after the infection, your chances of having a heart attack are 250% higher than someone who did not get infected. That's the value of this vaccine. Get a lot of that out of the way.
-The test in people over 60 years of age has already been completed. And what's next?
-A similar vaccine is being tested in pregnant women. We will have to see if it works as well as in older adults.
-When do you think the vaccine can be ready to protect newborns?
-We always have to wait. Each population is different. A newborn is different from a 70-year-old person. Hopefully it will be soon. Likewise, there have been excellent results with monoclonal antibodies from other companies. There, accessibility will depend on the cost of the product.
-Do pregnant women get the same vaccine as those over 60?
-It is conceptually the same vaccine in the case of Pfizer.
-Then it can be assumed that it will have the same effectiveness.
-We have to wait for the results of the study. We cannot extrapolate data from one study to another.
Respiratory syncytial infection significantly increases the risk of going to intensive care in the case of older people, which is why the vaccine was initially tested in people over 60 years of age (EFE).
-You have already tested the vaccine against respiratory syncytial that Pfizer made, but you are doing another study.
-Yes, we are testing a vaccine from Moderna with the same objective. It is very powerful for our group to advance with two products from sophisticated companies almost in parallel. And it is a great satisfaction, since these studies did not come to Argentina before and they started to come because of our work.
-Why are two of the world's largest laboratories interested in respiratory syncytial virus?
-To achieve this kind of goal you have to galvanize a lot of efforts that are often disjointed or scattered. What the World Health Organization and the Gates Foundation did to a large extent was to make respiratory syncytial the focus of a lot of researchers, international agencies and companies.
-Is COVID-19 finished?
-When wefirst met it, COVID was a wild animal and now it's a household pet. It will still cause colds, fevers and sore throats but, in the vast majority of cases and barring unforeseen events, it won't cause more than that.
-What comes after having tested the respiratory syncytial vaccine, which is what you have studied all your life?
-To continue working. And, above all, the beginning of what I consider to be the best project of my life. Without a doubt, the most transformative and generous project in which I have ever participated. But it has nothing to do with vaccines. If it works as we imagine, it will turn around a paradigm that has been anchored in society since the industrial revolution. It is a project that will change the fate of thousands and thousands of children, and not through any therapy.
-Can we know anything else?
-No, notfor now. One step at a time.
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