Lewis: Hi, and welcome to Your Health, Quickly, a Scientific American podcast series!

Fischman: On this show, we highlight the latest vital health news, discoveries that affect your body and your mind.  

Every episode, we dive into one topic. We discuss diseases, treatments, and some controversies. 

Lewis: And we demystify the medical research in ways that you can use to stay healthy.

Lewis: I’m Tanya Lewis

Fischman: I’m Josh Fischman

Lewis. We’re Scientific American’s senior health editors. Today we’re talking RSV vaccines. After decades of effort, we may be on the cusp of having several safe vaccines and other treatments for this nasty virus.

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Lewis: If you have small children, [or as my friends with kids like to call them, adorable germ factories] you’re probably heard of—or had—RSV. 

That’s short for respiratory syncytial virus. 

It infects most of us by the time we’re two or three years old, and it keeps infecting us throughout our lives. 

Last fall we had an especially bad RSV season, because the COVID pandemic changed some of the patterns of seasonal viruses. 

Fischman: You’re saying that COVID made RSV even more widespread than normal. How does that happen? 

Lewis: COVID precautions essentially delayed RSV infections because everyone was social distancing…. 

…. but then we had a really big wave once kids started going back to school again and all got sick at the same time.

Lewis: The symptoms of RSV are often similar to the common cold. But in very small babies and in older adults, it can sometimes be pretty dangerous. 

Barney Graham: RSV causes severe respiratory disease in young children. And it's the leading cause of hospitalization in children under five, cumulatively, and it also causes severe illness in the elderly. 

Lewis: That’s Barney Graham—

Graham: I’m Senior Advisor for Global Health Equity now at Morehouse School of Medicine in Atlanta. Previously, he was deputy director of the Vaccine Research Center at NIH in Bethesda.

Lewis: You might have heard of him, mainly because he and a team of scientists at the NIH’s Vaccine Research Center were instrumental in developing the technology for the mRNA COVID vaccines.

Fischman: He was actually working on RSV vaccines when the pandemic hit and he turned to COVID. His team’s work on those shots changed the world, protecting millions of people. 

And the scientists ended up on the cover of TIME magazine. But RSV has never been far from Graham’s mind.

Lewis: RSV was discovered in 1956, around the same time that the first polio vaccine was developed. 

Scientists started to work on a vaccine for RSV in the early 1960s. But those early efforts were marred by some serious problems. 

Like the polio vaccine, the first RSV vaccine was based on a whole inactivated virus. In a clinical trial in 1965, it was tested in children under the age of six months. 

But the trouble started that winter —

[CLIP: Music]

Graham: …that  vaccine, that whole inactivated vaccine was tested in about 31 children compared to another group of controls. But among those 31 children during the next winter season—66’, 67’—just after Christmas 20 out of 31 were infected and 16 of those 20 had to go to the hospital, and two of them died.

Lewis: It was really a terrible tragedy. Basically, the vaccine enhanced the disease’s severity because it produced the wrong kind of immune response in the children. Graham started his RSV career wanting to understand why — 

Graham: I worked 20 years on what was the cause of the vaccine enhanced illness?

Lewis:  Graham started collaborating with scientists Jason McClellan and Peter Kwong on a better RSV vaccine design. 

RSV infects cells using a protein called the “F glycoprotein.” When it fuses with the host cell, the protein “unfolds” from a so-called pre-fusion form to grab hold of the cell membrane, and then “refolds” into a post-fusion shape. 

The early vaccines failed because they were based on the post-fusion form. So when it was given to kids, their bodies made antibodies that only weakly attacked the pre-fusion form. This resulted in the vaccine making the disease more severe, not less.

Fischman: Wait a second. I get that there are pre-fusion and post-fusion forms. What I don’t quite understand is why does this whole process of vaccination make the disease more severe than the "no vaccine" condition?

Lewis: That’s a great question. The antibodies that targeted the post-fusion form still produced an immune response, but it was more of a state of hyperinflammation, which turned out to be dangerous. So Graham’s team turned their attention to targeting the pre-fusion protein.

Graham: Once we had that structure and learned how to stabilize it and keep it in that shape, it turned out to be a very good vaccine antigen. 

Lewis: That brings us to today: several companies have now developed vaccines using this protein structure-based approach. 

Pfizer and GSK are both testing a vaccine for adults over 60 and one for pregnant people, which could protect their babies up to six months after birth. And several of these—especially the ones for older adults—appear to be getting close to FDA approval.

And it’s not just vaccines—for children under the age of six months, who are most vulnerable to a severe infection, several companies are also making monoclonal antibodies for RSV. 

A product called Nirsevimab, made by AstraZeneca, is already approved in Europe, and it’s been accepted by the U.S. FDA for review.

Graham: Well it's exciting for us and gratifying. Multiple things are in very advanced development or near the stage of licensure, so we are going to have products for RSV.

Lewis: Graham told me the FDA will likely decide on the antibody product and some of the vaccines for the elderly by July or maybe even earlier. So things are really moving along.

Fischman: In fact, just a few weeks ago, the FDA’s committee of independent medical advisors met, and they went over the latest data on the two RSV vaccines for that older group. 

Their info came from the trials you mentioned, plus some other tests. 

Lewis: Overall the efficacy rates were pretty impressive: GSK’s vaccine was about 83 percent effective at preventing infection in the lower respiratory tract in adults 60 and older and 94 percent effective at preventing severe disease. Pfizer’s vaccine, meanwhile, was 67 percent effective at preventing infection and 86 percent effective at preventing severe disease. 

But that’s not the whole story.

Fischman: No, it’s not. I watched the FDA advisory hearing, and I gotta tell you the committee wasn’t completely happy. 

[Start CLIP: FDA Advisory Audio]

Unidentified Doctor: The public is very skeptical, and in order to maintain the trust that the FDA gets from the public and perhaps to rebuild that trust, we need to make sure that we’re really careful about the safety of a vaccine before we send it out.

[End CLIP: FDA Advisory Audio]

They were worried by two side effects that cropped up. 

Fischman: One is called acute disseminated encephalomyelitis. That’s when the brain or spinal cord rapidly swells up. There were two cases in trials of about 15,000 people with the GSK vaccine.

Lewis: The other worry was Guillain-Barré syndrome, a rare nerve disorder which causes weakness and sometimes paralysis. It usually begins in the hands and feet and can spread to the whole body. 

Fischman: Yeah, it happened in one person with the GSK vaccine and in two people with Pfizer.  The concern is that these conditions occur less frequently when they’re in the general population. 

So in the trials they could have something to do with the vaccines. And that really bothered the FDA advisors. 

Lewis: But it’s also possible that the cases were coincidences, because with just 1 or 2 cases, the numbers are really too small to say if there’s really a safety issue. 

Meanwhile, the GSK maternal RSV vaccine trial was halted because of a safety signal, meaning they also saw some kind of side effect that needs to be investigated further. The Pfizer maternal vaccine trial is still ongoing. 

Fischman: In the end, the advisors voted to let the applications for the older adult vaccines go forward. That’s going to take months, and the scientists really want to see more safety data as these trials keep going. 

So RSV vaccines aren’t a done deal. But things are probably heading toward approval.

Lewis: Yeah, I’d put a bet on it. I’m also keeping an eye on what’s happening with the antibody products for young kids and the maternal vaccines. RSV is still a serious disease in small babies, and the more we can do to protect them, the better.

Writer Tara Haelle is writing an online news story for us on the long road to an RSV vaccine, so you can read more about it there.

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Lewis: Thanks for listening!

Fischman: Your Health Quickly is produced and edited by Tulika Bose, Jeff Delviscio and Kelso Harper.

Lewis: The show is one of Scientific American’s Science, Quickly podcasts.  Subscribe to Science, Quickly wherever you get your podcasts.

Fischman: And don’t forget to go to Sciam.com for updated and in-depth health news. 

Lewis: We’ll be back in two weeks. Talk to you then!