Respiratory Syncytial Virus is responsible for more than 30 million respiratory infections and 50,000 deaths per year in children under five years of age worldwide. Why the start of a Phase III clinical trial could be crucial for children's health
Progress in the fight against respiratory syncytial virus, with Argentina as one of the key countries in the trial of a vaccine that could alter the impact of the virus on children's health (Getty)
Respiratory syncytial virus is a common viral disease and causes lung and respiratory tract infections in people of all ages. In infants and young children it is the main cause of bronchiolitis and can lead to severe complications such as pneumonia with the consequent need for oxygen and prolonged hospitalization. It is estimated that this pathogen generates 30 million respiratory infections and more than 50,000 deaths per year, worldwide, in children under five years of age and causes one third of deaths in children during the first year of life.
In view of this scenario, and despite the fact that in recent years different therapeutic strategies have been developed, such as monoclonal antibodies, which collaborate with the body's defense against infections caused by this virus and are aimed at preventing children from becoming seriously ill, and the vaccine for pregnant women (to be applied between 32 and 36 weeks) recently included in the National Vaccination Calendar, which seeks to generate antibodies in newborns, this immunization is presented as another "strategy to avoid the development and worsening of the symptoms", as highlighted by pediatrician Gonzalo Pérez Marc(MN 110.813) and Principal Investigator of the Hospital Militar Central.
It is an intranasal pediatric vaccine intended for children between 6 and less than 22 months of age, which will begin to be investigated in Argentina. The aim of this Phase III clinical trial is to evaluate the efficacy, immunogenicity and safety of this immunization which, in addition to providing protection against the pathogen, could become a turning point in the pathology, since it could "reduce the burden and spread of the disease among children", thus reducing the spread of the virus, said the physician specialized in Clinical Pharmacological Research.
Nasal vaccination, when delivered directly into the upper airways, is intended to provide an effective barrier against the entry and spread of RSV among younger children (Lancaster University).
Pediatrician Gonzalo Pérez Marc pointed out that the pediatric nasal RSV vaccine has the potential to decrease viral load and the spread of the virus among children (Christian Gaston Taylor).
- In recent years, different strategies have been developed for RSV, monoclonal antibodies and vaccines for pregnant women, which are intended for infants, the same age group for which this vaccine is intended. Don't they overlap?
- You have proven strategies, such as vaccines for older adults and pregnant women, with the latest ones protecting newborns. In addition, monoclonal antibodies, some of 5 doses and now one of one dose, together with those under research, for infants. But it is always necessary to investigate new pediatric vaccines, in addition to antivirals. Not all countries have the same vaccination rate, besides, there is a group of people who do not get vaccinated or, if they do, they do it out of date or, even if they are vaccinated within the indicated weeks, they do not manage to generate the antibodies in their babies because, for example, they are born earlier. There are also immunosuppressed populations and a group of children who, for some reason, will not have the necessary immunity. For these groups, among others, we are investigating this vaccine.
With the vaccine for pregnant women, of which we were part of the study, one thinks that there will be sustained efficacy over time, due to the immune memory response(NdeR: the capacity of the organism to initiate the "defense" against a pathogen after having recognized it the first time), but this has not been proven, since it is a series of mechanisms of the organism that are concatenated. In spite of this, some children will still be at risk; that is why this is a new vaccination strategy. But there is also another point. With the strategies that are already in place, it is possible that the age at which bronchiolitis appears may be shortened. So, at the end of the day, all these strategies will end up complementing each other so that, instead of developing, the presence of severe disease will be reduced. Now, there will be a great positive debate to know which is the best mixed strategy for each child. Always, the more tools, the better.
The importance of vaccination during childhood is evidenced by the constant scientific effort to develop safer and more efficient immunizations. (Getty)
For a nasal vaccine against RSV?
The nasal mucosa has been identified as the main focus through which respiratory viruses penetrate into humans, according to research that delves into early immune reactions to pathogens such as RSV (respiratory syncytial virus), SARS-CoV-2 and influenza virus. This is due to the characteristics of nasal tissues, which trigger significant immune responses before they even descend to affect lung areas.
These previous studies had found that viruses not only rapidly infect the nasal turbinates (key bones in breathing, covered by expandable tissues that, when inflamed, block airflow and make breathing difficult), but also cause a significant increase in viral replication in this area. This is the gateway for viruses and the site from which the innate immune response that prepares the body for a more efficient defense against infection is triggered. Ultimately, it is through this same site that the pathogens that humans face each year naturally enter the body.
In short, it is the first line of defense provided by antibodies in the mucosa, secretory immunoglobulin A (IgA-s), which is complemented by intraepithelial lymphocytes and T and B cells in the tonsils. In other words, it is the battlefield where these sentinels of immunity receive the front line of viruses. But they are also essential for the generation of an immunological memory to counteract future infections.
The search for long-term immunity against respiratory pathogens is guiding researchers toward vaccines that promise substantial changes in public health.
"With vaccination, what you want to prevent is always severe disease. Nobody cares if you have a mild disease, if you avoid severe disease. That's what the COVID vaccines achieved, they turned the virus from pandemic to endemic. This vaccine, unlike the systemic (injectable) ones, seeks to reduce the spread of the disease because they protect the upper airways", said Perez Marc.
In the words of the expert, with the usual vaccines, the virus has to enter the organism to "awaken" the memory immune response, which remains latent. However, the presence of antibodies decreases and, from time to time, they have to be boosted. "With systemic vaccines, at the end of the day, the virus is 'negotiated' to be mild in the upper airways, so that it does not spread to the lower airways, which are the lungs. And since viruses are replicating beings, they look for a way to find a place where they can multiply or spread. Achieving a vaccine that not only generates good systemic immunity, but also has a good response in the upper airways allows, therefore, to reduce not only the disease in children, but also the transmission to other children", he pointed out.
"In previous studies, it was seen that these vaccines are effective in reducing, by more than 50%, medical consultation, since the symptoms are so mild that they do not go to the hospital. Even mild illnesses, such as a cold, are reduced," he explained.
How the study for pediatric RSV nasal vaccine will be conducted
The aim of the study, according to Equipo Ciencia's CEO, is to evaluate the efficacy, immunogenicity and safety of the pediatric intranasal vaccine in a multinational, multicenter, randomized, placebo-controlled Phase III clinical trial. To this end, at a global level, they will seek to include some 6,300 children between 6 and less than 22 months of age.
The countries where the trial will be carried out are the United States, England and France, in addition to Argentina. Throughout the national territory, it will be carried out in 6 health centers. "In the country we do not have a specific number, it will be as many as we can enroll. At the Central Military Hospital we are aiming at about 500, who will be followed up for a year," said Pérez Marc.
The administration of this vaccine will be done through a nasal spray and there will be two doses with an interval of two months between each one. "The choice of a one-year follow-up is because, after that time, in the youngest children, the immune system, which was immature before, has adapted to not hyperreacting. In addition, with the older ones we will go up to 3 years of age. In this way, in those under one year old we will follow them in their first two winter seasons and in the older ones in their third and fourth ones", he concluded. At the same time he emphasized that they are recruiting volunteers on the web: www.equipociencia.com.
