Infants and children sick with RSV are flooding pediatricians' offices and children's hospitals across the United States, due to an early surge of the common childhood virus this year.
But within one or two “sick seasons,” doctors expect to have on hand long-sought tools to help blunt the impact of respiratory syncytial virus (RSV).
As many as four new RSV vaccine candidates could soon be sent for review by the U.S. Food and Drug Administration, experts say, and dozens more are in testing or under development.
“There are 30 or something [vaccine candidates] out there. I've lost count,” said Dr. Greg Poland, director of the Mayo Clinic's Vaccine Research Group in Rochester, Minn.
Additionally, a new monoclonal antibody developed by drugmaker Sanofi has already been approved in Europe to protect infants against RSV infection.
While not a full-fledged vaccine, the drug Beyfortus (nirsevimab) would be the first treatment available to protect infants against RSV during their first year of life. Sanofi said the drug has been submitted to the FDA for approval.
On the vaccine front, pharmaceutical companies Pfizer and GSK have announced solid results from phase 3 clinical trials in seniors for their respective RSV vaccine candidates. This is usually the last step in testing before a company submits its vaccine to the FDA for approval.
Pfizer has also announced positive phase 3 clinical trial results in pregnant women and their newborns, with antibodies produced by the mom's immune system crossing the placental barrier to produce protection in the fetus.
The vaccine was more than 80% effective in protecting newborns against RSV during their first 90 days of life, and about 70% effective through the first six months, Pfizer announced in a news release earlier this week.
“The babies that are born will have a significant benefit from the mother's vaccination for their first six months of life, and that's when a lot of the RSV illness is a primary concern,” said Dr. Aaron Glatt, chair of infectious diseases with Mount Sinai South Nassau, in New York.
Based on those data, Pfizer said it intends to submit its vaccine for FDA review by the end of 2022.
Two other major pharma competitors, Janssen and Moderna, have their own RSV vaccine candidates in clinical trials, Poland added.
Dozens of RSV vaccines in the works
RSV is typically a minor infection that produces sniffles in most kids, but social distancing precautions taken during the pandemic meant that fewer children have been exposed to it, and thus haven't developed immune protection against it.
“You suddenly have a whole larger population of kids that haven't been exposed to RSV that are now getting it,” Glatt explained. “You may have a 2-year-old, a 3-year-old and a 4-year-old all at the same time getting it, whereas normally you'd only have the 2-year-olds getting it.”
RSV is particularly dangerous for infants because it can cause bronchiolitis, an inflammatory condition that clogs the tiny airways inside the lung. Infants who struggle to draw breath often cascade quickly into other health problems because they usually won't eat or drink, making them weak and dehydrated.
However, RSV can cause lasting damage in toddlers and young children as well, said Dr. Sean Liu, medical director of the COVID Clinical Trials Unit at the Icahn School of Medicine at Mount Sinai, in New York City.
“Children who are hospitalized with severe RSV have a higher prevalence of developing asthma as they grow up,” Liu added. “So, it would be really exciting to see this vaccine prevent all that harm that RSV does.”
The drug companies are all champing at the bit to have their vaccines reach the market, so much so that Dr. Ashish Jha, head of the White House COVID-19 Response Task Force, told CNN that he's “hopeful” at least one RSV vaccine will be available by next fall.
Although optimistic, Poland warned against buying all the hype related to RSV vaccines. It will take some time for the vaccines to be approved for children, since the regulatory pipeline requires they first be tested in adults.
“I'm alarmed at some of the headlines and some of the people they're interviewing, because they say things like, 'Well, we'll have this vaccine next year and the era of respiratory infections during the winter will be over,'” Poland said. “No. No, it won't. I guarantee you it won't.”
All this activity comes after decades of disappointment in the hunt for an RSV vaccine.
The first RSV vaccine trial conducted in the United States in the 1960s turned out to be “horrible,” Glatt said, “and through lack of full understanding of immunology actually worsened things for patients.”
Two children died in the clinical trial, which involved an inactivated virus. The vaccine caused a phenomenon called antibody-dependent enhancement, where the antibodies produced by a vaccine actually make a virus more virulent and harmful.
“Basically, research on RSV vaccines stopped after that,” Poland said. “I mean, that was it. Nothing happened for decades.”
Vaccine developers finally suss out RSV's secrets
The hunt for an RSV vaccine picked up in the early 2010s when a team of researchers isolated the structure of the virus' F-protein, the site that allows it to attach to human cells, Poland said.
The F-protein works in a similar way to COVID's spike protein, but once it's “fused” with a human cell it changes shape.
The mistake with the first vaccine candidate was that it created antibodies based on the F-protein's shape after it had already gotten into a human cell, said Liu.
“In essence, it was ineffective antibody, but it fooled the body into thinking that there was protection there,” Liu said.
The new research figured out how to stabilize RSV's F-protein in its “pre-fusion” state, before it attaches to a cell, Poland said. That gives the human immune system an accurate target against which to form antibodies.
“That suddenly opened the gateways into RSV vaccine research, which has still proceeded very, very slowly because of concern and fear over antibody-dependent enhancement,” Poland said. “In the field of vaccinology, this is generating immense excitement, and rightfully so.”
But Poland noted that neither of the most advanced vaccine trials, by Pfizer and GSK, have had results published in a peer-reviewed medical journal yet.
Instead, the companies have been announcing early results from their phase 3 trials in news releases and at medical meetings.
For example, GSK announced at the October annual meeting of the Infectious Diseases Society of America that its RSV vaccine had been more than 90% effective in protecting seniors against the virus.
The earliest protection U.S. children might receive against RSV could instead come from nirsevimab, the Sanofi monoclonal antibody approved this week in Europe.
Sanofi has said it hopes the treatment will be available in the United States for next year's RSV season.
Nirsevimab is administered to infants in a single shot, either at birth or before the RSV season begins. Because the jab supplies antibodies against RSV rather than promoting a natural immune response, the protection is immediate but short-lived.
But clinical trial results showed that nirsevimab was nearly 75% effective in warding off severe cases of RSV, according to a report published earlier this year in the New England Journal of Medicine.
The U.S. Centers for Disease Control and Prevention has more about RSV.
SOURCES: Greg Poland, MD, director, Vaccine Research Group, Mayo Clinic, Rochester, Minn.; Aaron Glatt, MD, chair, infectious diseases, Mount Sinai South Nassau, New York; Sean Liu, MD, PhD, medical director, COVID Clinical Trials Unit, Icahn School of Medicine at Mount Sinai, New York City