Results in 7900 women in 18 countries indicate that the drug developed by Pfizer is 81.8% protective against severe bronchiolitis in the first three months of life; coverage maintained at six months
A maternal vaccine to protect newborns from bronchiolitis that is under investigation has just yielded the most expected results so far with immunization in pregnancy to prevent infection in babies during the first six months of life. In the country, each year, this disease caused by respiratory syncytial virus (RSV) generates some 20,000 hospitalizations and some 600 avoidable deaths in children under one year of age, or almost half of all deaths due to respiratory infections at that age.
In the Phase III clinical trial, the vaccine being developed by Pfizer achieved 81.8% protection against severe RSV infection in the first 90 days of life, with efficacy remaining at 69.4% at six months, the U.S. laboratory said today in a statement.
The results of an interim analysis of the Maternal Immunization Study for Safety and Efficacy (Matisse) were released after the data on the RSVpreF vaccine candidate analyzed met these predefined regulatory success criteria. For this reason, the company anticipated that it will send the data for publication in a peer-reviewed scientific journal and that, by the end of the year, it will request authorization for use from the regulatory agencies of the United States, Europe and the countries where the research is being carried out, including Argentina.
If approved, it will be the world's first maternal vaccine against bronchiolitis virus in infants.
In the Matisse study, 7400 pregnant women under 49 years of age from 18 countries have been participating since June 2020. At random, half received a 120 µg dose of RSVpreF and the other half a placebo version, starting at the end of the second trimester of gestation.
Stage
At this stage, the efficacy, safety and immunogenicity (ability to generate an immune response) of the vaccine against severe LRTI is evaluated in the infants of women immunized towards the end of gestation. The mothers were followed up to six months after delivery and the infants were followed up to one year of age. A subgroup of boys will be followed for two years.
"This is the analysis that opens the evaluation of the vaccine to the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and also Anmat. It is the first vaccine that clearly prevents bronchiolitis, so it is of great importance in pediatrics," said Fernando Polack, scientific director of the Infant Foundation and consultant in New York for the design of the studies to evaluate this vaccine.
Over the past 25 years, Infant's team not only mapped the impact of RSV on the global pediatric population, which provided the World Health Organization (WHO) with data to prioritize the development of a bronchiolitis virus immunizer over other germs, but also worked with other world-renowned groups to decipher why vaccines being developed against RSV were failing. "Without understanding this, we would not have been able to move forward with a maternal vaccine to protect the baby," Polack said.
The map of the impact of bronchiolitis in pediatrics revealed that the infection is the main cause of death in Argentina, as in other countries, between one month and 12 months of life. "One in every 1000 healthy newborns dies, especially in poor areas. In areas with more services, children die because of basic diseases that make them more vulnerable, and in areas such as the suburbs, the outskirts and rural areas, they die because the need for care is greater than what can be provided by the available health structure -recalled the researcher-. Half of the most vulnerable die at home. For years, public health in Latin America confused these deaths with sudden infant death due to lack of healthcare support. They are the vulnerable among the vulnerable."
A vaccine, in a context of the current crisis, which makes it impossible to reverse this scenario, would counteract the effects of a virus that is the main cause of death in the youngest children. "Half of the children are infected in the first year of life. Thirty percent have bronchiolitis with some degree of severity that demands medical attention. In Argentina, pediatric hospitalization units are overflowing in winter," said Polack. With a vaccine with these results, there would be a paradigm shift, since vaccination would prevent the hospitalization of 80% of severe cases. This would leave hospitals with the capacity to dedicate themselves to the care of the most serious and vulnerable, which at the same time optimizes the use of healthcare resources."
At the same time, given that RSV infection could open the way to bacterial co-infection that causes pneumonia, preventing bronchiolitis could also lead to reducing it, which is under study. "And all this without the need to make major structural changes in health policies, but with something as simple as incorporating a vaccine into the National Calendar," said Polack.
Argentinean Labor
In Argentina, 942 women are participating in the Matisse study; most of them have already had their babies and the follow-up, with the remaining deliveries, will last another year. Pediatrician Gonzalo Pérez Marc is one of the principal investigators of the trial in the country, coordinating four of the five participating centers in different jurisdictions. For him, who has been researching RSV with Polack for years, the results known today mark a before and after in pediatric care.
"It is an achievement that most of the medical community still has no notion of the impact it is going to have -says Pérez Marc in a dialogue with LA NACIÓN after the dissemination of the results-. Bronchiolitis [due to RSV] is one of the main concerns that all pediatricians in the world have every year."
That's, among other reasons, because one of the leading causes of respiratory sequelae in newborns is from bronchiolitis. "Having a vaccine that changes the world scenario is a milestone. We have to see how it works, depending on how it is applied in each country once it is approved, but it should certainly be a calendar vaccine," added Pérez Marc, head of Research and Teaching at the Maternal and Child Unit of the Central Military Hospital, one of the local sites of the clinical trial, and director of Clinical Studies and Hospital Management at the Infant Foundation.
Last August, Pfizer had announced that a dose of the bivalent vaccine RSVpreF had also been shown to be effective in people over 60 years of age. Argentine volunteers also participated in that study. With the results known today, progress is being made towards "having both groups at the extremes of the population, the youngest and the oldest, protected with the same effective vaccine at the same time".
The obstacle to developing an immunizer against RSV was in deciphering how the virus could enter a cell and infect it. Once this "key" was detected, progress was made with the vaccine. In this case, it is a fusion protein on the surface of the virus, but in its prefusion state (hence the name of the candidate vaccine). The immune response obtained is more stable than with the post-fusion protein because it is more similar to that triggered by the virus, as Pérez Marc explained to this newspaper about the challenge posed by this virus. A study by the U.S. National Institutes of Health had shown that antibodies specific to that form of the fusion protein prevented the virus from infecting cells.
"It is an incalculable pride and emotion for our team. Doing clinical research with pregnant women and newborns in public and private centers in the country, also in the midst of the pandemic, is a true source of pride. On the first day of pediatric residency," Pérez Marc gave as an example, "the first thing a physician learns is to recognize the signs and symptoms of bronchiolitis and how to treat them. Therefore, managing to prevent this disease, for us, as pediatricians, is of enormous relevance."
