New RSV vaccines are on track to make this one of the last bad cold seasons

All over the country, pediatric hospitals are packed to the gills. Although soaring rates of several cold viruses are to blame, one baddie in particular is responsible for much of the mayhem: respiratory syncytial virus, otherwise known as RSV.

RSV generally causes cold symptoms but can also lead to severe lung inflammation or infection in very young and very old people. And it’s started off cold season with a bang: As of October 22, babies under a year old were being hospitalized at rates six times higher than they were at the same point in 2019, and the overall hospitalization rate was seven times higher for people of all ages.

Every year, hundreds of children die of RSV, and tens of thousands more are hospitalized. But for a change, this year brings some good news: It might be the last time the virus wreaks this kind of havoc.

After decades of failed efforts to produce an RSV vaccine, several highly effective ones are finally on the verge of approval. On Tuesday, Pfizer announced that in a trial, its vaccine — which is given to pregnant people so infants are protected at birth (more on that later) — prevented 69 percent of severe RSV cases among infants 6 months old and younger. Also on the horizon are vaccines for older adults, and new monoclonal antibodies (i.e., human-made proteins that function like antibodies in our immune systems) to help prevent infections.

All told, experts say these products are effective enough to prevent more than three-quarters of severe disease in both age groups.

Experts anticipate these products could be broadly available for use within one to two years — if drug approval and recommendation processes at the Food and Drug Administration and Centers for Disease Control and Prevention go smoothly. That means that, barring any surprises, babies and adults in the US could be able to rely on them for RSV protection as soon as next fall. Expect global vaccine authorities to weigh in on these products soon, as well.

“If we can keep the babies out of the ICU and keep them from dying, we’ve won a huge victory,” said Amy Edwards, a pediatric infectious disease specialist at Rainbow Babies and Children’s Hospital in Cleveland. But it wouldn’t just be a win for babies: “More adults have died from RSV than most people realize,” she said, “RSV vaccine could be a game changer for them as well.”

It’s all because of a scientific breakthrough that happened less than a decade ago. Here’s how the secret to RSV vaccine development was found — and why the proliferation of discovery it sparked is such a big damn deal.

RSV is an overlooked cause of illness and death, with no great preventive options

RSV disease is one of the first pediatric illnesses that young pediatricians learn to fear, said Edwards. Babies with the infection have terrible coughs and make wheezing noises as they struggle to move air through their swollen airways. “Once you’ve seen it, it’s like you never forget it,” she said.

RSV itself is nothing new, especially during the cooler months. “There are bad seasons and less bad seasons, but there’s always RSV,” said Edwards.

In the US, the infection leads to about 58,000 hospitalizations and 100 to 300 deaths among young children each year, making it the country’s top cause of hospitalization in infants. Although it’s a particularly risky infection for babies born prematurely and for those with lung problems or heart abnormalities, about 40 percent of American infants who died of RSV over the past few decades were otherwise healthy.

RSV is also an underrecognized cause of pneumonia in adults, causing up to 120,000 annual hospitalizations among people over 65. It’s overlooked in part because adult doctors don’t think of it as an adult disease, said Helen Chu, a University of Washington infectious diseases doctor and researcher who specializes in emerging respiratory diseases. Even when hospitalized adults test positive for RSV, she said, that detail is often omitted from the hospital discharge codes (which play a big role in insurance billing but are also used to monitor disease trends).

In a talk at a conference of the Infectious Diseases Society of America in late October, Chu compared the impacts of RSV and influenza on Americans over 65, noting that RSV causes as many as 12,700 deaths in seniors each year — not too far shy of the 21,000 deaths caused annually by the flu.

However bad RSV is in the United States, it’s worse globally. Every year, it causes an estimated 120,000 infant deaths worldwide and as many as 55,000 adult deaths, most of them concentrated among people living in poverty and breathing polluted air.

There is currently no approved antiviral treatment for RSV in either adults or children, and the one preventive option that currently exists is far from perfect.

That option is palivizumab (brand name Synagis), a monoclonal antibody developed 25 years ago to protect high-risk infants. However, it has to be given monthly during RSV season, and most insurance companies require physicians to go through a lengthy approval process to get the drug’s high cost covered for their patients. Plus, although it does prevent hospitalization in high-risk babies, it’s not clear how cost-effective it is.

Babies need something better — something affordable that can protect all infants, not just the highest-risk ones, from this seasonal scourge. Adults, too, need something to protect them from a virus that reliably causes an immense amount of disease — ideally, something that’s as good as a flu shot, or better.

RSV vaccines are super effective, and soon, they’ll be for everyone

The first time scientists tried to develop an RSV vaccine, in the 1960s, it failed miserably, actually leading to more severe RSV infections in the babies who received it.

Although that tragedy slowed vaccine development somewhat, it didn’t entirely dissuade researchers. But over the next few decades, they made little progress, largely due to some unique features of RSV’s surface proteins.

Those proteins are shape shifters, taking different forms depending on whether they’ve invaded — or fused to — a human cell. And 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, with incredible results.

In her conference talk, Chu presented data on five different vaccines for use in adults and six products for use in younger populations, including vaccines for pregnant people and both monoclonal antibodies and vaccines for babies and young children.

What she then described would have seemed inconceivable a few years ago.

Chu presented data from phase three trials — advanced vaccine studies that test a product’s safety and effectiveness. Overall, these products are knocking it out of the park, preventing more severe RSV cases at a range of 70 to 86 percent effectiveness. Writ large, that means they have enormous potential to prevent hospitalization in many of the people most vulnerable to the worst effects of RSV.

Vaccinating mothers during pregnancy will protect their infants

Of the many options currently under development to protect babies from severe RSV infection, the one that will likely get the most use is a vaccine that would be given not to babies themselves, but to the people who carry them before they’re born, said Edwards.

When someone is immunized against RSV during pregnancy, the antibodies they produce in response get transferred in large quantities to their infant, providing a strong wall of protection over the first few months of their lives. “Maternal vaccination — I mean, that’s the ultimate monoclonal antibody,” said Edwards, and “a lot of moms are used to it.” The strategy, which relies on antibodies transferring naturally from pregnant people to fetuses while they’re in the womb, is used to protect babies from diphtheria, tetanus, and pertussis (with the maternal Tdap vaccine), the flu, and SARS-CoV-2.

In particular, Pfizer’s RSV vaccine candidate for pregnant people prevented 85 percent of RSV cases in their babies from getting bad enough to require bringing them to a clinic or hospital.

But even if the expecting parent does not get vaccinated, there will still be options to protect their babies: Several monoclonal antibody options will likely be on the table, which prevent between 70 and 75 percent of more severe symptoms. In contrast to the maternal vaccine, these are intended to be given directly to infants after birth. Importantly, both the maternal vaccine and the monoclonal antibody will be available to protect all infants, whether they have medical conditions or not.

Even with the vaccines and antibodies, there will still be some challenges. The protection babies get from maternal vaccination or monoclonal antibodies lasts less than a year. However, some children — like those with medical conditions such as heart abnormalities — need longer-lasting protection. (Most children are at highest risk for bad RSV in their first six months of life, and should be well covered by maternal vaccines and antibodies.)

The strategy for refreshing their immunity is still up in the air, said Chu. It might involve getting repeat doses of monoclonal antibody — or it might eventually involve giving a vaccine to a young child directly. Two candidates for that are currently in the early stages of investigation and so will not be widely available for several years. It will be up to the FDA and the CDC to determine how best to keep infants protected in their early years.

Meanwhile, three vaccines for adults are in phase 3 trials, and at least two more candidates are at earlier stages of development. The three closest to the finish line prevent 80 to 86 percent of severe RSV infections in people over 60.

In the US, all that stands between these vaccines and the people who need them is finishing the trials (for those still in progress), submitting data for review to federal agencies, and approval and recommendation by the FDA and the CDC.

The current RSV season shows just how badly these products are needed

Chu suspects these vaccines’ benefits will take many Americans by surprise. “I don’t think that the general public is either aware of RSV or realizes what a huge change this will be,” she said. She also underscores just how important the basic science underlying some of these vaccines has been. McLellan’s protein stabilization discovery also helped facilitate the development of Covid-19 vaccines by providing a technique for stabilizing SARS-CoV-2’s spike protein. “It is a momentous achievement that they were able to do that — and that’s how things moved so quickly,” she said, referring to the lightning pace of production of the first Covid-19 vaccines.

The discovery’s original purpose — to enable RSV vaccine development — will also do enormous good. “I’m very excited, and for a variety of reasons,” said Edwards. “One: babies shouldn’t die,” she said. But also, as these products become available, she said, “most of us believe that we’re going to see a reduction in hospitalization — and that can only work in our favor.”

If only we had these vaccines and antibodies available this year. RSV is currently surging, and hospitals hollowed out by the pandemic are struggling to meet the need. Many hospitals increase their staffing at this time of year, said Edwards, but that’s becoming harder to do because of shortages across the medical professions.

“Granted, this season has been worse than most,” she said. “We don’t necessarily anticipate having this bad season every year.”

“But as staffing shortages become more and more acute around the country, we would expect even smaller and smaller surges to incapacitate hospitals,” she said.

In other words, we’ve never needed an RSV vaccine more urgently than we do right now.

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