Spanish scientists in search of a vaccine

Nothing is more sensitive than the health of babies. Therefore, what would we think of a virus that is diagnosed every year at 33 million young children worldwide and what causes three million hospitalizations? No, this is not a new pandemicRather than a fairly common problem that was named in the middle of the 20th century: respiratory syncytial virus (RSV). It is so common that 90% of children are infected before the age of two and the normal thing is that nothing happens, since most have no symptoms other than those of a cold. However, a small percentage of cases are complicated by pneumonia, so it is the leading cause of hospitalization in babies under one year of age. The bad news is that there are no vaccines or treatments. The good news is that Spanish scientists are a little closer to achieving them.

According to the Spanish Society of Pediatric Infectology (SEIP), 1% of children have to be admitted in their first months for this problem and, of these, 10% reach the FIA. During the first year of life, RSV is responsible for 80% of bronchiolitis (inflammation of the lung airways) and remains the leading cause of pneumonia (inflammation of the lungs themselves) among children under five years of age. The situation in countries with fewer resources and poorer health care is more serious, so that there are 118,000 infant deaths annually worldwide for this problem.

Why this variability between mild and severe cases? The premature babies and those with chronic problems they have much more risk. In any case, the experts believe that it is necessary to consider that RSV is a health problem of the first order and to bet in a decisive way on the investigation. So Europe has decided to take this problem very seriously in all its dimensions: we need to study the virus and its consequences more, we need to improve surveillance systems, we need vaccines and therapies. Over the years, various groups of researchers have collected data in the RESCEU project (acronym for ‘Respiratory Syncital virus Consortium in Europe’), including its impact on public health and the economy. Now, they are going to take a step with a new initiative, the PROMISE project (‘Preparing for RSV Immunization and Surveillance in Europe’), which aims to be decisive, uniting public research and the pharmaceutical industry.

“There is going to be a revolution, it is a field in which imminent advances will be made with the arrival of vaccines, antivirals and monoclonal antibodies “, states in statements to Technician Federico Martinón-Torres, head of the Pediatric Service of the Hospital Clínico de Santiago, who participates in this initiative. For years, his team has been monitoring newborns to study the true incidence of RSV. “We study the virus, its molecular evolution and the patients, to find predictive markers of severity and see who may have sequelae,” he explains. The Galician Health Service (Sergas) is one of the three Spanish entities participating in this international project. The other two are the Barcelona company Teamit Research and the Foundation for the Promotion of Health and Biomedical Research of the Valencian Community (Fisabio).

Close to getting vaccinations

Precisely, from the Vaccine Research Area (AIV) of Fisabio, the researcher Javier Díez Domingo and his team are immersed in several clinical trials of vaccines in phase 3 with Spanish participants. Nevertheless, Finding an effective immunization against RSV is not easy. The first vaccine was achieved in the 1960s, but it was a failure, because it was inactivated with formaldehyde and caused more severe disease in vaccinated children than in the placebo group. In general, animal models fail in the preclinical phase, because it is very difficult to reproduce the infection suffered by humans in them. Clinical trials are not easy either, because the ideal would be to administer the vaccine before two months of age, but the immune system is still immature and there may be interference with maternal antibodies. In this sense, experts consider that two different types of vaccine should be developed, one for infants and one for older children and adults. “It is the virus that causes pneumonia most frequently in infants, but for years it has been known that it affects the elderly a lot, not as much as the flu, but also to a great extent,” he says.

Within the framework of this project, Fisabio researchers are working with three different vaccines that opt ​​for different strategies to overcome all the problems that have made immunization unfeasible until now. All of them are already in phase 3 of clinical trials (the last one before a possible authorization) and are having participants from Valencia. One of them would apply to pregnant women. “The idea is that the mother pass the defenses to the baby”says Diez. The other two vaccines are aimed at the elderly. “The advantage is that this virus does not change, it is not like the flu virus, so if it works, it would be for the long term and with significant effectiveness,” he highlights. At the moment, they have already vaccinated hundreds of people throughout the past month of October and the objective in this fall e winter will be checking the effectiveness.

The development of vaccines aimed directly at infants is encountering more difficulties. The Fisabio researchers were working on a project that, for the moment, has come to a standstill. The reason is that its vector was an adenovirus, that is, the same as those developed by AstraZeneca and Janssen against the covid. The problems they had in the case of the coronavirus have caused that project to be canceled until more data is available to support the safety of this type of vaccination strategy.

Asthma and other implications of RSV

Apart from vaccines, there is another very interesting tool, monoclonal antibodies. “They are defenses that are exclusively directed at a part of the virus, so that they would be able to block it. There is one that has been on the market for many years and is very expensive, so it is only used for very high-risk children, those who are very premature or have lung or lung diseases. heart“explains the scientist. The success of this strategy is important, since it reduces hospitalizations by half, but a new monoclonal antibody, which is currently in phase 3 clinical trials (in this case, Spanish researchers are not participating), promises much greater efficacy, with a duration of protection of up to six months.

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In recent years, knowledge of VRS, of the immune system and how the two interact, but there is still a long way to go. Experts are betting on looking for biological markers to anticipate cases that may evolve worse and have sequelae due to infection, a matter still little known. “We could know which children are going to have more serious complications and, above all, anticipate possible long-term consequences,” says Díez. The inflammation that this virus produces in the bronchi causes a serious injury and, according to one hypothesis, would be related to asthma cases in children. In other words, if a child suffers from a significant RSV infection, they are a clear candidate for asthma. In addition, other studies find an association with chronic lung diseases in adults. “The global impact is much greater than known”, highlights the expert.

You have to see how the body behaves in children with more serious problems and, from there, seek treatments. There is currently no therapy beyond the support in the most serious cases, that is, supply oxygen. Although an antiviral was developed decades ago, the side effects advised its withdrawal. However, today new perspectives are opening, because “once we know the mechanisms of the disease and why there are children who respond worse, we would enter personalized medicine”.

The influence of the pandemic

RSV is seasonal and, precisely, from this time on, cases skyrocket. However, the covid has caused quite a bit of uncertainty. With social distance, masks and hygiene measures, the usual numbers of this virus decreased significantly. Many children will have almost certainly gotten rid of a contagion, but perhaps this is not as good news as it seems. The first data from some countries, with a significant incidence out of season, and some studies they already alerted that the end of the restrictions could bring a major outbreak.

The first data seem to confirm the fears. In 2020 there was no RSV in Spain, but this year everything is changing. “In summer there was a major epidemic in some communities, totally outside its usual period, and now there is also a significant incidence and very early. Normally, the cases start in the middle of November and we have already been a month“, says Diez.”Epidemics have a lot to do with the circulation of the virus and with defenses. After a year without RSV, children born in 2020 and 2021 have not had contact with this virus, so the susceptible population is very large and it is distributed much faster. It was foreseeable, what we did not imagine is that cases would occur outside the usual months, but after a year and a half without cases, anything could happen “, confesses the expert.

According to Martinón-Torres, one of the big problems is that “there is no active surveillance system for RSV“, unlike in the case of covid or the flu. In recent weeks, cases have begun to accumulate and already threaten to collapse the pediatric system. For this reason, probably “the peak of cases will be much higher than in previous years, but we cannot know what will happen, because what is not measured cannot be anticipated,” he laments. The lack of follow-up comes from afar: “Pediatricians have been asking for it for a long time and it is time for it to start.”

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