Updated September 22, 2023 18:20
Every fall, as the air turns cold and the leaves turn red, pediatric ICUs begin to prepare for an onslaught of the virus known as RSV.The main reason is not influenza or the new coronavirus, but respiratory syncytial virus (RS virus). baby is in the hospital, every year. The small airways can become inflamed, making breathing difficult in the sickest cases. RSV is also deadly and takes lives at the other end of the age spectrum. 6,000~10,000 older Americans every year.
But for decades, there was no way to stop seasonal outbreaks of the virus. The quest for a vaccine has always ended in failure. And suddenly, the vaccines started working.
This year, doctors will receive not just one, but multiple new vaccinations to prevent respiratory syncytial virus. Three drugs have received FDA approval in quick succession in recent months. Nilsevimab, a type of passive immunization for babies too young to receive proper vaccines.Pfizer’s vaccine is compatible with both. Adults over 60 years old and pregnant mother, who can pass on immunity to their baby. And finally, GlaxoSmithKline vaccine Together, they herald a new era for RSV.
It’s no coincidence that these three new RSV shots are released at the same time. They all succeeded because they all target specific weaknesses in the virus, while other viruses have failed. First identified in 2013. This strategy of finding the weakest points in viruses also applies to other pathogens, and experts say it could revolutionize vaccine design for other diseases.In fact, it was secretly used COVID vaccine from Pfizer and Moderna. Scientists originally perfected the idea with RSV, but the urgency of the pandemic led them to repurpose it into a coronavirus vaccine that is being rushed forward. But this year, RSV has an opportunity.
“After more than 65 years, we are finally in a really good position,” said Asuncion Mejias, an infectious disease physician at St. Jude Children’s Research Hospital.
The first attempts to produce an RSV vaccine began shortly after the outbreak of the virus. discoverya trial took place in 1956, but the earlier trials ended so disastrously that they had a chilling effect for decades.
it had It started with a promise. Early vaccines were modeled after the successful polio vaccine and used a chemical called formalin to inactivate the virus. But a surprising turn of events occurred when an infant who received her RSV vaccine early on later contracted the virus. 80% had to be hospitalized— compared to only 5% in the control group. Two of the infants had their lungs destroyed and died. The vaccine was worse than no protection. That made the disease even more severe. “It was a really dire situation,” says Ann Falsey, an infectious disease doctor at the University of Rochester.Scientists spent years figuring out why vaccines were such a hit. The wrong part of the immune system But we didn’t come close to producing an effective vaccine. The field has come to a standstill.
Then, in 2008, a chance encounter led to the final breakthrough. A newly minted young Ph.D. A protein structure researcher named Jason McClellan has started a new job at the National Institutes of Health working on HIV vaccines. However, there was no longer room on his fourth floor in the lab he joined, so he was placed in another one on his second floor. There he met Barney Graham, a virologist who had been trying to solve the RSV mystery since the 1980s. He persuaded McClellan that the virus was also worth looking at.
By then, scientists were focused on at least reasonable vaccine targets. Just as COVID uses the spike protein to infect cells, RSV uses a protein called F, which stands for “fusion,” to physically fuse its virus particles to human cells. However, F has two forms. One is a very unstable pre-fusion state, and the other is a much more stable post-fusion state. And once it switches to a postfusion state, which can occur spontaneously, “there’s no going back,” McClellan said.
When the RSV vaccine is manufactured, all F proteins eventually switch to their postfusion state. However, antibodies against postfusion F were less effective. Mr. McClellan immediately understood why. He discovered that highly potent neutralizing antibodies bind to a specific site, the very tip of prefusion F. This site is lost when the protein reconstitutes into its postfusion form. In that case, Graham told me, “you lose potency by a factor of 10 to 1,000.” An effective RSV vaccine must target prefusion F.
The team knew what to do, but there was a practical dilemma. So how can F be stabilized in its pre-fusion form so the team can incorporate it into a vaccine? McClellan re-arranged the protein slightly and added molecular “staples” to make the protein more stable. Filled the holes in the structure. These changes caused F to be frozen in its prefusion shape. When the research team tested this version of the vaccine on mice, the results couldn’t be more clear. The vaccine elicited the highest levels of neutralizing antibodies Graham had ever seen in his 30 years studying RSV. “This is it,” McClellan remembers thinking.
Pharmaceutical companies soon contacted us and the competition began. (The experts in this article, like nearly everyone working on an RSV vaccine, have received research grants, consulted with one or more companies developing a vaccine for RSV, or have received research funding in other ways. ) Today, Pfizer and GlaxoSmithKline announced that their newly approved RSV vaccine targets the prefusion F protein, similar to AstraZeneca and Sanofi’s infant antibody nirsevimab. . Both the vaccine and the antibody injection induce immunity to RSV in her. Vaccines stimulate the immune system to produce its own antibodies, whereas nilsevimab injects the antibodies directly.
Trials for all three shots had already begun when the coronavirus pandemic hit. However, the trial was delayed because RSV has nearly disappeared during social distancing. Meanwhile, McClellan and Graham devised a similar molecular trick to stabilize the coronavirus’ spike protein, later used by Pfizer and Moderna in their vaccines. (However, as in the case of RSV, stabilization of COVID was not the make-or-break; AstraZeneca’s COVID vaccine was effective even without this modification.) But instability Fusion proteins are found in many different classes of viruses besides RSV. McClellan, now at the University of Texas at Austin, is working on attacks against the prefusion structures of other stubborn viruses, including cytomegalovirus and Crimean-Congo hemorrhagic fever. (Graham is now a professor at Morehouse School of Medicine.) This approach, called structure-based vaccine design, could unlock new ways to target once-elusive viruses.
For RSV, this fall and winter will be a test to see how well the shots will work in the real world. As the saying goes, vaccines don’t save lives. Vaccinations will be given. Falsey, a doctor at the University of Rochester who specializes in researching respiratory syncytial virus in older adults, is concerned that too few Americans over 60 will be eligible for the new vaccine this year.a CDC Advisory Committee It determined that older Americans could be vaccinated through “shared clinical decision-making” with their doctors, but stopped short of fully recommending vaccination. That would encourage private insurance companies to cover vaccinations under the Affordable Care Act.May cost money over $300. But this shot is poised to have a bigger impact on young children. The same CDC panel today endorsed the Pfizer vaccine for pregnant women and had already recommended the antibody shot nilsevimab for newborns. (Most babies only need one or the other.)
Nilsevimab is an alternative to an existing RSV antibody injection called palivizumab, which is not widely used. Palivizumab targets the low potency sites in both pre- and post-fusion F and should be administered up to 5 times per season (1 time for nilsevimab). $1,500 per dose. For these reasons, it has been reserved for the most at-risk babies, such as premature babies whose lungs are underdeveloped. But St. Jude’s Mejias said most of the babies who ended up in the hospital were healthy to begin with, so the older vaccines didn’t have a big impact on overall hospitalizations. Nilsevimab is intended for more widespread use, and this vaccination has been approved for all infants in their first RSV season. “It’s going to change the way we manage and treat RSV,” Mejias told me.Even babies can use it starts in October. And if all goes as planned, pediatric ICUs could be a little quieter this winter.