The FDA Approves a Breakthrough Vaccine 50 Years in the Making
May 4, 2023 (Vox.com) – On Wednesday, the Food and Drug Administration approved the first vaccine that protects against respiratory syncytial virus, otherwise known as RSV.
This is a big moment in the fight against a major scourge. Researchers have been working to create an RSV vaccine for more than half a century. And it’s not an exaggeration to say RSV vaccines could save hundreds of thousands of lives each year on a global scale.
RSV generally causes cold symptoms, but can also lead to severe lung inflammation or infection in very young and very old people. Each year, it causes up to 160,000 hospitalizations and 10,000 deaths among older Americans, and as many as 55,000 adult deaths globally. People with heart and lung disease and weakened immune systems are at the highest risk for severe RSV disease.
RSV season usually starts in the autumn and is worst in the winter. The vaccine, known as Arexvy, was approved for adults 60 and over, will likely be recommended by the CDC in June and available in time for people to receive it this fall, according to reporting in the New York Times.
Young babies, especially newborns born prematurely, are also at high risk for bad disease due to RSV: Annually, the virus causes up to 80,000 hospitalizations and 300 deaths in American children under 5, and leads to 2 million outpatient visits. The virus also leads to an estimated 120,000 infant deaths worldwide each year.
Right now, this news does not impact pediatric populations. But there’s hope on the horizon: Several vaccines that would protect babies and children — and a number of other adult vaccines — are currently either under FDA review or at earlier stages of development.
RSV was a major contributor to the “tripledemic“ that flooded hospitals last winter. As these vaccines come to market, they could dramatically change the face of cold and flu season for the better.
For now, here’s what you need to know.
The vaccine is highly effective and has generally mild side effects
Arexvy, which is made by drug manufacturer GSK, is one of two adult RSV vaccines the FDA reviewed at a March 1 meeting. In trials, the vaccine reduced the risk of lower respiratory tract illness in adults over 60 by nearly 83 percent, and the risk of severe illness by 94 percent.
The vaccine, which is given as a single injection, is built using the kind of conventional technology that preceded mRNA technology used to create many Covid-19 vaccines. It’s built using a chunk of the RSV virus and a couple of additional molecules. The result is called a recombinant vaccine because it combines pieces of a virus with other products that stimulate the immune system. Other vaccines built with this technology include the ones used to prevent whooping cough, meningitis, and shingles.
Side effects related to the vaccine were generally mild and resolved within one to two days. The most common side effect was mild to moderate pain at the injection site, and a smaller number of people reported fatigue after the injection.
The FDA will monitor for severe side effects
For the most part, the Arexvy vaccine appears to be safe. However, the FDA has its eye on a few uncommon side effects that it will watch for carefully as more and more people get the vaccine. Although these were very rare among people who took part in the vaccine trials, they’re severe enough to merit close monitoring.
In one trial, where each group had 12,500 participants, 10 Arexvy recipients and four people who got a placebo had atrial fibrillation, an irregular and rapid heart rhythm that can lead clots to form in the heart. (The condition is extremely common among older adults and sometimes reverses itself; it’s treatable with blood thinners when it does not.) One participant in this trial developed Guillain-Barré syndrome, a condition in which the immune system attacks nerve cells, leading to weakness and sometimes paralysis.
In another trial with 2,500 people each in the Arexvy and placebo groups, two people who received the vaccine developed an inflammatory condition affecting the brain and spinal cord, one of whom died.
The FDA is requiring GSK to monitor for the incidence of all these conditions among people who get the vaccine going forward.
As ever, the question for the agency is whether the vaccine’s side effect risks are greater than RSV risks. Time will help answer that question.
This is a huge win!
People first began trying to develop an RSV vaccine in the 1960s. Why did it take so long to make it work?
RSV’s surface proteins are shape-shifters, taking different forms depending on whether they’ve invaded — or fused to — a human cell. To complicate matters, their pre-fusion shape is wildly unstable. That meant that for a long time, researchers’ only option was to use the protein’s post-fusion shapes as targets for new vaccines.
As a result, for years, RSV vaccines could only recognize viral particles after they’d invaded cells — too late to make much of a difference. To make a better vaccine, scientists really needed a clear picture of what those surface proteins looked like before cell invasion.
In 2013, structural biologist Jason McLellan, now at the University of Texas at Austin, figured out how to get that picture: He worked out a way to stabilize a surface protein in its pre-fusion form, then described it in great detail. That discovery meant researchers could now create vaccines that targeted an earlier stage of RSV infection — and they did.
Arexvy is just the first downstream result of this discovery to be approved by the FDA, and more will likely follow soon. Pfizer’s RSV vaccine for adults will probably be approved later this month; Moderna has said it’s expecting its adult vaccine to be authorized in the first half of this year; and multiple companies are working on vaccines to protect babies and toddlers under 2.
Overall, we’re in for a lot more good news about RSV vaccines in the near future.