Respiratory syncytial virus (RSV) is dangerous for newborns. The risk of disease can already be reduced with antibodies. Why pediatricians are still waiting for a vaccine.
During the pandemic, the highly contagious respiratory syncytial virus (RSV) was overshadowed by the coronavirus. Now, a pathogen that causes severe inflammation in the lungs of newborns and infants is back in the headlines — twice. The number of cases in Switzerland has been rising steeply since the end of October, which is pushing children’s hospitals to the limits of their staff and bed capacity. At the same time, there is also good news about how children could be better protected from the MS virus that is circulating around the world.
One news item concerns possible vaccinations. American pharmaceutical company Pfizer recently announced the results of a clinical trial of its RSV vaccine candidate. This protected children from severe RSV infection by a good 80 percent in the first three months; after another three months, the protective effect is still almost 70 percent, the company writes.
Annoying company communication without study data
“We have been waiting decades for RSV vaccination in pediatrics,” comments Pfizer’s Christoph Aebi, chief physician at the University Clinic for Pediatrics at the Inselspital Bern. At the same time, it bothers him that the company communicates its results without publishing the study data. “Until I’ve seen this data, I can’t say much,” emphasizes the professor.
The practice of early corporate communication without review of study data is uncomfortable for many clinicians and researchers. According to Aebi, this policy was understandable during the pandemic, when time was of the essence. For the RSV vaccine, it is motivated purely economically. Critics fear that the pharmaceutical industry will lose confidence and thus weaken the acceptance of vaccination in the population.
Timely communication without data is probably mainly due to the competitive situation. Because in addition to Pfizer, other companies such as GlaxoSmithKline, Janssen, Bavarian Nordic and Moderna have their RSV vaccine candidates at the start. All are striving for quick market approval. Vaccines should benefit not only newborns and infants, but also elderly and debilitated adults who can also become seriously ill. “For everyone else, the MS virus causes a harmless cold,” says Aebi.
The peculiarity of the now presented Pfizer vaccination is that it is not administered to the newborn, but to the mother during pregnancy. Immunization causes the woman to develop antibodies against RSV, which are then transferred to the baby through the placenta and breast milk. “This would not be the first vaccination that is primarily to protect the child, but is administered to a pregnant woman,” says Aebi. This concept is also applied to whooping cough. Flu vaccination, which can also be administered during pregnancy, on the other hand, serves primarily to protect women.
“The maternal pathway is the silver bullet with the MS virus,” says Aebi. Because the most important thing is that the baby has enough antibodies at birth. If that were the case, roughly 40 percent of RSV-related hospitalizations could be prevented, the doctor estimates. Since antibody protection declines relatively quickly, as with Corona, after a few months one could consider revaccinating the child – then actively – against RSV. This covers a complex time window. “But this is all still speculation,” Aebi points out. Specific vaccination recommendations require not only an approved vaccine, but also additional clinical studies.
The antibody is a milestone, vaccination would be a breakthrough
No speculation is another protection option. Since 1998, doctors have been able to give protective antibodies as a drug (palivizumab) to infants who are at particular risk of severe RSV infection. According to studies, the risk of admission to the hospital and treatment in the intensive care unit can be reduced by 50 to 60 percent. This makes RSV-related deaths very rare in rich countries like Switzerland.
“The antibody is a milestone in RSV,” says Aebi. But immune prophylaxis requires a monthly injection into the child’s muscle. And it costs 6,000 to 7,000 CHF per child and winter. Palivizumab is therefore only used in high-risk babies, such as extremely premature babies and newborns with lung or heart disease.
But this could change the second news regarding RSV protection. The European regulatory agency EMA recently approved a new antibody with a longer lifespan (nirsevimab). It only needs to be administered once before the beginning of the RSV season, which greatly simplifies the treatment. An application for drug approval is being prepared for Switzerland.
“But this drug is likely to be many times more expensive than vaccination,” says Aebi. This is a big problem, especially in poor countries where many infants still die from RSV infection. And there is another pitfall: “If we only treat children who are clearly at risk, then the impact on the burden of disease and the burden on children’s hospitals is only a drop,” emphasizes the doctor. Of the 1,500 newborns and infants who have to be hospitalized in Switzerland each year for RSV-related dyspnoea and associated inadequate food and fluid intake, more than 90 percent are healthy and have no known risk factors.
Deaths during the first vaccination attempts
Aebi is convinced that only vaccination will bring a breakthrough in RSV. It has been in the works since the 1960s. An early attempt at vaccination resulted in a fiasco in 1966 that killed two infants. The formalin-attenuated vaccine virus not only had no protective effect on the children. After contact with the wild virus, they got sick much more than unvaccinated children.
This phenomenon is now known as “antibody-dependent amplification”. The vaccine promotes the production of antibodies. However, they cannot neutralize the virus, but open the door to the cells, so to speak. This increases infection.
Such a disaster cannot be expected for new vaccine candidates that are in the final stages of clinical trials, Aebi says. This is mainly due to the fact that these vaccines are very specific against RSV. Just as antibodies against the spike protein are formed during coronary vaccination, RSV is about the so-called F-glycoprotein. This allows the virus to enter the cell and multiply there. This protein is blocked by RSV vaccination as well as drug-based immune prophylaxis. This should prevent infection.
According to the world organization, the first vaccination against RSV should be available in the near future. “Many pregnant women should then be routinely vaccinated,” says Aebi. Because some of the risk factors that cause a baby to become seriously ill after an RSV infection are not known before birth. This includes, in particular, significant premature birth.