After sixty years of research, the first vaccines against respiratory syncytial virus (RSV) could finally arrive in 2023, while already in the coming months we could count on a new preventive monoclonal antibody, just approved by the European Commission.
The race for an Rsv vaccine
The first clinical trials of vaccines (with an inactivated virus) date back to the 1970s, but they were not successful. The “race” for the development of a prophylaxis resumed at the end of 2013, when the research team of Jason McLellan (now at the University of Texas at Austin) discovered that a particular structure of a protein – the F protein, used by virus to invade human cells – was a good target to induce the immune system to produce antibodies and prevent infection.
Since then, several companies have begun developing a vaccine, and four – GSK, Janssen, Moderna and Pfizer – are now in an advanced stage of testing. GSK and Pfizer, in particular, are testing their vaccine in both over 60s and pregnant women, with the aim of immunizing the unborn. And the first results, recently announced by both pharmaceutical companies, are positive. Novavax was also experimenting with a vaccine for pregnant women, but its early results weren’t nearly as encouraging.
The challenge: to prevent the disease in children
The immature immune system of newborns is a complex challenge, because in the first two months of life, babies do not develop a robust response to many vaccines (which is why most childhood vaccinations are given after this period). However, unborn babies can be immunized while still in the womb, because antibodies produced by the mother pass through the placenta before birth, and through the mother’s milk afterwards. “It is certainly necessary to protect the little ones from birth, because the infection is more serious the younger the child is, especially if contracted in the first three months of life”, explains to Salute Susanna Esposito, full professor of Pediatrics at ‘University of Parma and head of the Infectious Diseases and Vaccinations Technical Table of the Italian Society of Pediatrics: “The difficulty of thinking about a vaccination for children in the first months of life – continues the expert – lies in the fact that it is a critical period for the development of the immune system, and it is not certain that in newborns it responds effectively. For this reason, an alternative is to vaccinate mothers, as is already the case for the prevention of influenza and whooping cough in the first 6 months of life. On a social level, however, it may not be easy to reach pregnant women where compliance with vaccination during this particular period of life is very low. The other emergency concerns the elderly ”.
How dangerous is respiratory syncytial virus?
RSV is a very common and contagious virus, causing annual and seasonal epidemics. In our hemisphere it circulates mainly from October to March. Although very often the symptoms of the infection are mild, it causes millions of hospitalizations every year and, for some at-risk categories – such as young children and the elderly – it can be fatal. Every year there are about 33 million new infections from the RSV virus globally in children, and hospitalizations – according to statistics prior to Covid – settled at 3.2 million in the first five years of life. In this age group, the infection causes 48,000 to 75,000 deaths every year. The most severe symptoms occur in the first two years of life, but in recent years it has been seen that even among older children and adolescents – especially asthmatics – the respiratory syncytial virus can be very dangerous. Among adults, the infection can be severe especially over the age of 75, causing lower respiratory tract infections, and is responsible for 335,000 hospitalizations per year and 14,000 deaths globally. “Considering these numbers – underlines Esposito – it is clear why the issue of prevention from these infections has become a priority”.
The results on investigational vaccines
Let’s go back to developing vaccines. Last August Pfizer published the results of the third phase of trials on 37,000 adults over 60. The recombinant vaccine RSVpreF, designed to target the two strains A and B of the virus, has been shown to be effective in preventing lower respiratory tract infections. the most serious, in 85.7% of cases. At the beginning of November, the same pharmaceutical company announced the first results of the experimentation carried out on over 7,000 pregnant women, who received, with a single injection, the vaccine or the placebo. To evaluate the efficacy, both the level of antibodies in pregnant women and newborns (and their trend over time), and the respiratory infections that appeared in children in the first months of life were analyzed: according to what the company communicated, prophylaxis it prevented the most severe forms of lower respiratory tract infections in hospitalized children in 80% of cases in the first 90 days of life, and in 79.4% in the first six months.
As for the elderly population, the data on GSK’s candidate vaccine (directed against the two strains A and B) are also positive, so much so that the Food and Drug Administration (FdA) has just granted the priority review of the clinical study data, which involved about 25,000 over 60s. The results, presented in mid-October, show an overall vaccine efficacy of 82.6% against Rsv lower respiratory tract disease and 94.1% against the severe form.
The pathway of monoclonal antibodies for newborns
In addition to vaccines, another prophylaxis strategy is based on monoclonal antibodies. “Considering the seasonality of the virus – continues Esposito – the vaccine in pregnancy cannot be the only strategy for prevention. In our country, for example, if a woman gave birth in April, the vaccine would cover the newborn only until September, when the virus begins to circulate in October. That is why solutions that directly affect newborns and infants are being studied. At the moment there are no advanced studies on pediatric vaccines, while a promising solution seems to be new monoclonal antibodies ”. Monoclonal antibodies, used in this case not for therapeutic but preventive purposes, aim to block the replication of the virus and to stimulate an immune response that prevents the development of the disease, just like vaccines do.
Palivizumab is currently approved and used in Italy, but only for premature births and frail babies considered to be at high risk in the first 12-24 months of life. The scenario, however, is about to change: the European Commission has, in fact, just approved another monoclonal antibody, nirsevimab (produced by the companies Sanofi and AstraZeneca), for the prevention of bronchiolitis and pneumonia caused by RSV in infants and children in their first season of possible contagion. The drug can be administered from birth (with a single dose, via intramuscular injection) and is effective for six months: according to the data of the clinical study that led to the approval, nirsevimab has been shown to prevent over 74% of respiratory complications from Rsv.