Medical breakthrough
Pediatrician and babies in Syracuse helped develop new RSV drug
BY AMBER SMITH
Babies finally have protection from the leading illness that puts them in the hospital, thanks in part to the tireless work of an Upstate doctor and his team — and three Central New York babies who were the first in the world to receive a shot of this new drug.
“I’m elated,” Joseph Domachowske, MD, said when the FDA announced its approval of nirsevimab this summer. The drug protects newborns from respiratory syncytial virus, or RSV. (Adults 60 and older have another medication to protect them from RSV.)
Domachowske spent more than three decades working on a way to fight RSV. He is a pediatrician at the Upstate Golisano Children’s Hospital specializing in pediatric infectious disease. RSV is the top cause of hospitalizations for babies under 6 months old, and the virus kills about 250,000 infants each year, mostly in developing countries without access to hospital care.
(Hear an in-depth interview with Domachowske about the drug and how it was tested. )
Nearly 5,000 newborns and young infants from all over the world were part of the studies. The first three received their single shots in Syracuse in January 2015. One was from a family with a history of RSV complications; the other two were twins born prematurely and therefore at increased risk for complications.
Those twins, Cassidy Meany and Stella Meany, were 8 years old when nirsevimab was approved. Their mother, Cheryl Meany, told Syracuse.com, “We feel really blessed we were a part of it. I can’t explain how excited and how happy I am for moms across the world who don’t have to take their babies to the hospital because they can’t breathe.”
Domachowske says nirsevimab consistently was 80 percent effective in preventing RSV hospitalizations and requires just a single dose as the RSV season — from fall to spring — gets started. “At last we can finally reduce the impact of these annual RSV epidemics,” he says. “I’m especially eager to watch RSV fall from its long-held No. 1 cause of hospitalizations among children in their first year of life.”
He predicts that hospitalization numbers could initially be cut in half. As more babies are protected in subsequent years, Domachowske expects fewer hospitalizations, fewer visits to the emergency department and a major decrease in the number of sick infants who are brought to pediatricians.
Nirsevimab, sold under the brand name Beyfortus, is not a vaccine but rather a monoclonal antibody product that provides a passive immunity.
Vaccines prompt the body to make antibodies to defend against diseases. In contrast, nirsevimab is a ready-made antibody that can bind to the virus and block it from infecting healthy cells.
Babies under 6 months old are at the highest risk for severe infection, so there’s not enough time to deliver a typical vaccine series to allow them to build immunity for the period of time they are most susceptible to severe illness. With this new treatment, the immune system doesn’t have to make anything.
This story appears in the 2024 Upstate Health magazine, Issue 1.
Upstate’s Joseph Domachowske, MD, was part of a worldwide team that developed a vaccine for the potentially deadly virus RSV. Photo by William Mueller.
Seniors can get RSV protection
The respiratory syncytial virus is also a threat to older people. The rates of hospitalization in people over age 65 from RSV are second only to those for influenza.
The Centers for Disease Control and Prevention recommends a single dose of RSV vaccine for adults 60 and older. The vaccine is also recommended for moms-to-be during weeks 32 to 36 of pregnancy, immediately before or during RSV season.
“With these combinations of prevention options, we’re hoping that we’ll have a less severe RSV season than last year,” said Upstate infectious disease chief Elizabeth Asiago-Reddy, MD. “Last year was a very severe RSV season that was somewhat unprecedented.”
Upstate’s Joseph Domachowske, MD, and other researchers across the globe tried multiple approaches over three decades that did not work against respiratory syncytial virus.
Then, at a conference in Argentina, some of the leading RSV researchers heard a protein chemist describe one of the proteins that sits on the outside of the RSV virus.
“My jaw hit the floor,” Domachowske recalls. Researchers had been focused on the wrong protein.
RSV particles have daggerlike things sticking out of the surface of the virus. As soon as the daggers touch a cell, to try to infect it, the handle of the dagger flips, and the structural component of the protein changes.
Researchers had been working on an antibody that would work after the dagger flipped. But it turns out, they needed an antibody that would be effective "prefusion" -- before the dagger touched the cell. “We’d been working on the confirmation of the wrong protein for decades.”
The second thing that was discovered right around the same time, he said, “was that if we take any antibody, these monoclonal antibodies in particular, and we change the part of the antibody that attaches to the cell — not the part that attaches to the virus, but the part that attaches to the cell — if we change it by just three amino acids, very small changes, it can enhance the half-life of these molecules from 19 days out to more than 120 days. So now we have the potential of making a very high neutralizing antibody against, really, whatever we want, that will last a fairly long time, out to five months, maybe longer.
This story appears in the 2024 Upstate Health magazine, Issue 1.
