After decades of unsuccessful research efforts, a protective vaccine for respiratory syncytial virus is finally within reach. Shots developed by Pfizer and by GSK are currently under regulatory review in the U.S. and their approval, if granted next month, will mark a long-sought milestone against a common and deadly infection.
On Wednesday, full results from two large clinical trials run by Pfizer were published in The New England Journal of Medicine, giving the medical community a fuller look at the data supporting that company’s vaccine in older adults and in pregnant women. The same journal published study results of GSK’s vaccine in older adults in February.
Pfizer’s data “move us closer to prevention of RSV illness in the young and old,” wrote Ruth Karron, a pediatrician and virologist at Johns Hopkins Bloomberg School of Public Health, in an editorial published alongside the results.
The company is currently expecting the Food and Drug Administration to decide on its vaccine’s approval for older adults by the end of May, and for pregnant women by August.
Respiratory syncytial virus, or RSV, is particularly dangerous for infants and the elderly. Children younger than six months are at higher risk of health complications and deaths, while older adults with underlying conditions are more likely to be hospitalized for RSV infection.
Pfizer’s RSV vaccine is a bivalent shot that targets both the A and B strains of the virus. In the larger of the two trials, a study called RENOIR that enrolled nearly 36,000 adults 60 years or older, vaccination proved 67% effective in preventing infections with at least two symptoms. The shot was 86% against more severe disease, with three related symptoms.
The data show that protection was durable, extending through the end of the first RSV season, and was consistent across subgroups. Researchers also reported Pfizer’s vaccine was 62% effective against acute respiratory illness due to RSV infection.
By comparison, results were more mixed in the maternal study, which enrolled nearly 7,400 pregnant women who were vaccinated prior to giving birth. Vaccination prevented medically attended severe RSV-associated lower respiratory tract illness in infants at 90 and 180 days following birth. The study’s other endpoint, measuring efficacy on RSV-associated lower respiratory illness more broadly, wasn’t met.
Researchers cautioned that the trial excluded women with high-risk pregnancies, infants of whom could be at higher risk of severe illness.
For protecting infants, doctors could soon have a monoclonal antibody developed by Sanofi and AstraZeneca that in testing proved 74% effective in preventing medically attended RSV-associated lower respiratory tract infection through 150 days. The drug was recently approved in Europe and is under review in the U.S.
Antibody drugs can be costly and might be limited to use in high-risk groups, however.
Researchers didn’t raise any major red flags on Pfizer’s vaccine safety in either trial. In RENOIR, rates of adverse events were low, albeit slightly higher among those who received the vaccine. During a February meeting, a group of FDA advisers noted some concern around rare instances of an autoimmune condition called Guillain-Barré, which occurred in one individual. (A similar condition known as Miller-Fisher was reported in another.)
Vaccinated participants in the maternal study experienced higher rates of local side effects such as redness and injection-site pain, as well as headache and muscle pain.
Experts at the February FDA meeting wanted to see more data showing Pfizer’s shot’s efficacy when co-administered with other vaccines, as well as in immunocompromised and higher-risk individuals. The advisers ultimately voted 7-4 in separate votes to endorse the shot’s safety and efficacy.
Even with limitations, Pfizer’s data are a step forward in a decadeslong attempt to develop a preventive RSV vaccine.
“These efforts have been made with care to avoid the tragic enhanced RSV illness that occurred in the 1960s in children who had not previously been infected with RSV and who received a formalin-inactivated RSV vaccine,” Karron wrote in her editorial, referring to an earlier type of shot.
More recent work by scientists at the National Institutes of Health gave researchers a leg up by solving the “prefusion” form of a protein RSV uses to latch onto and invade cells. This provided a clearer vaccine target, one that’s now been proven to elicit a stronger immune response.
Even with effective vaccines in reach, challenges still remain. “This progress is remarkable, but substantial additional work to guide decision-making and implementation is essential,” noted Karron.
The cost of the vaccine, if approved, will be an important factor in determining access, particularly in lower- and middle-income countries. More communication to convince expecting mothers of vaccination would be needed, too, according to Karron.
An FDA decision on GSK’s is due earlier in May than the month-end decision date for Pfizer’s. The regulator is expected to decide on Sanofi and AstraZeneca’s antibody by the third quarter.
Further out are Moderna and Bavarian Nordic, which are both developing their own RSV vaccines. The shortlist of competitors recently narrowed by one, however, as Johnson & Johnson revealed March 29 it is ending a large late-stage study of a once front-running shot.
Editor’s note: This story has been updated to include mention of other RSV vaccine developers.