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



All over the country, there are pediatric hospitals packed in gills. Although high rates Several cold viruses One villain in particular is blamed for much of the chaos: the respiratory syncytial virus, otherwise known as RSV.

Respiratory syncytial virus generally causes cold symptoms but can also lead to severe pneumonia or infection in the very young and the elderly. And the cold season began with great fanfare: as of October 22, children under one year old were hospitalized at prices Six times higher than in the same period in 2019, the overall hospitalization rate was seven times higher for people of all ages.

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

After decades of failed efforts to produce an RSV vaccine, several highly effective vaccines are on the verge of approval. Tuesday, Pfizer announce that in one trial, its vaccine — given to pregnant women so that babies are protected at birth (more on that later) — prevented 69 percent of acute respiratory syncytial virus cases among infants 6 months of age or younger. Also looming are vaccines for older adults and new monoclonal antibodies (that is, man-made proteins that act like antibodies in our immune systems) to help prevent infection.

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

Experts expect these products to be widely available for use within one to two years — if drug approval and recommendation processes at the Food and Drug Administration and the Centers for Disease Control and Prevention go smoothly. This means that, barring any surprises, children and adults in the United States can count on them for RSV protection as early as next fall. Expect global vaccine authorities to overburden these products soon, too.

“If we could get the kids out of the ICU and prevent them from dying, we would have achieved a major victory,” said Amy Edwards, MD, a pediatric infectious disease specialist at Rainbow Hospital for Children and Children in Cleveland. But that wouldn’t just be a win for kids: “More adults have died from respiratory syncytial virus than most people realize,” she said, “and the RSV vaccine could be a game-changer for them, too.”

All because of a scientific breakthrough that happened less than a decade ago. Here’s how the secret to developing the RSV vaccine was found and why the spread of the discovery it made is such a big deal.

RSV is a neglected cause of illness and death, with no significant preventive options

RSV is one of the first pediatric illnesses young pediatricians learn to fear. Edwards said. Infected children have a terrible cough and make wheezing sounds as they struggle to move air through their swollen airways. “Once you see it,” she said, “it’s like you’ll never forget it.”

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

In the United States, infection leads to about 58000 hospitalizations and 100 to 300 deaths of young children each year, making it the country’s leading cause of infant hospitalization. Although it is a particularly risky infection for babies born prematurely and for those with lung problems or heart abnormalities 40 percent Of the American children who died of RSV within the past few decades were otherwise healthy.

RSV is also an unknown cause of pneumonia in adults, causing up to 120,000 annual hospitalizations Among people over 65 years of age. It’s been overlooked in part because adult clinicians don’t consider it an adult disease, said Helen Chu, MD, an infectious disease researcher at the University of Washington who specializes in emerging respiratory diseases. She said that even when adults in a hospital test positive for RSV, those details are often omitted from Hospital discharge codes (Which plays a big role in insurance billing but is also used to monitor disease trends.)

Speaking at an American Infectious Disease Society conference in late October, Chu compared the effects of RSV and influenza on Americans over 65, noting that RSV causes as many as 12,700 deaths in older adults each year — not too shy of 21,000 deaths from influenza annually. .

Although there is bad RSV in the United States, it is worse globally. Every year causes appreciation 120,000 child deaths All over the world and up to 55000 adult deathsMost of them are concentrated among people who live in poverty and breathe polluted air.

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

That option is palivizumab (trade name Synagis), a monoclonal antibody developed 25 years ago to protect high-risk children. However, it must be submitted monthly during RSV season, and most insurance companies require physicians to pass Lengthy approval process To cover the high cost of medication for their patients. Additionally, though Hospital admission is not prohibited In children at high risk, it is not clear how Cost-effective he is.

Kids need something better – something affordable that can protect all children, not just the most vulnerable, from this seasonal pest. Adults also need something to protect them from a virus that reliably causes an inordinate amount of illness – ideally, something as good as a flu shot, or better.

RSV vaccines are very effective, and soon they will be available to everyone

The first time scientists tried to develop an RSV vaccine, in the 1960s, it failed miserably, in fact resulting in more severe respiratory syncytial virus infections in the children who received it.

Although this tragedy slowed vaccine development somewhat, it did not completely dissuade the researchers. But over the next few decades, They’ve made little progresslargely due to some unique features of RSV surface proteins.

These proteins are modulators of shape, taking different shapes depending on whether they invade – or fuse – a human cell. To complicate matters, its pre-merger shape is highly unstable. This meant that for a long time, the researchers’ only option was to use the post-fusion protein forms as targets for new vaccines.

As a result, for years, RSV vaccines were not able to identify viral particles until then They invaded cells – too late to make a big difference. To make a better vaccine, scientists really needed a clear picture of what those surface proteins look like Before cell invasion.

In 2013, structural biologist Jason McClellan, now at the University of Texas at Austin, figured out how to get this image: He has come up with a way to stabilize the surface protein in its pre-fusion shapeThen describe it in great detail. This discovery means that researchers can now create vaccines that target an early stage of RSV infection. They have achieved amazing results.

Speaking at the conference, Chu presented data on five different vaccines for use in adults and six products for use in younger groups, including vaccines for pregnant women and both monoclonal antibodies and infant and young child vaccines.

What I described then would have seemed unimaginable a few years ago.

Zhou provided data from Phase 3 trials — advanced vaccine studies that test product safety and efficacy. In general, these products get them out of the garden, preventing more serious cases of RSV within the 70 to 86 percent effectiveness range. Significantly, this means that they have tremendous potential to prevent hospitalization in many of the people most vulnerable to the worst effects of RSV.

Vaccinating mothers during pregnancy will protect their babies

Of the many options currently being developed to protect children from acute respiratory syncytial virus infection, the one that is likely to receive the most use is a vaccine that will not be given to the children themselves, but to the people who carry them before they are born. Edwards.

When someone is immunized against respiratory syncytial virus during pregnancy, the antibodies they produce in response pass in large quantities to their infant, providing a strong wall of protection for the first few months of their life. “Mother’s vaccination — I mean, this is the absolute monoclonal antibody,” Edwards said, and “A lot of moms are used to it.” The strategyIt is based on antibodies that are passed naturally from pregnant women to their fetuses while they are in the womb, and is used to protect babies from diphtheria, tetanus, whooping cough (with the mother’s Tdap vaccine), influenza and SARS-CoV-2.

In particular, Pfizer’s RSV vaccine candidate for pregnant women prevented 85 percent of their children’s RSV cases from getting so bad that they would need to be brought to a clinic or hospital.

But even if the expecting parent isn’t vaccinated, there will still be options to protect their children: Many monoclonal antibody options are likely to be on the table, preventing between 70 and 75 percent of severe symptoms. Unlike the mother’s vaccine, it is intended to be given to babies immediately after birth. Importantly, both the mother’s vaccine and the monoclonal antibody will be available to protect all children, whether or not they have medical conditions.

Even with vaccines and antibodies, there will still be some challenges. The protection that babies get from the mother’s vaccination or monoclonal antibodies lasts less than a year. However, some children – such as those with medical conditions such as heart abnormalities – need long-term protection. (Most babies are most susceptible to bad RSV in the first six months of life, and should be well covered with the mother’s vaccinations and antibodies.)

Zhou said the strategy for reviving their immunity is still up in the air. It may involve getting repeated doses of a monoclonal antibody — or it may eventually involve administering a vaccine to a young child directly. Two candidates for this purpose are currently in the early stages of investigation, and therefore will not be widely available for several years. It will be up to the Food and Drug Administration and the CDC to determine how best to keep children protected in their early years.

Meanwhile, there are three vaccinations for adults Stage 3 Trialsand at least two other candidates are in early stages of development. The three closest to the finish line prevent 80 to 86 percent of acute respiratory syncytial virus infections in people over 60 years of age.

In the United States, all that stands between these vaccines and the people who need them is to finish trials (for those still in progress), submit data for review to federal agencies, and approval and recommendation by the Food and Drug Administration and the CDC.

This RSV season shows how badly these products are needed

Chu believes that the benefits of these vaccines will surprise many Americans. “I don’t think the general public is either aware of RSV or aware of how hugely change this is going to be,” she said. It also underscores how important the basic science behind some of these vaccines is. The discovery of McLellan’s protein stabilization also helped facilitate the development of Covid-19 vaccines by providing a technique for stabilizing the spiky protein of SARS-CoV-2. “It’s a very significant achievement that they have been able to do – and that’s how things have gone so quickly,” she said, referring to the blistering pace of production of the first Covid-19 vaccines.

The original purpose of the discovery – to enable the development of an RSV vaccine – would also be useful. “I am very excited, and for a variety of reasons,” Edwards said. “First, children must not die,” she said. But also, with these products available, she said, “most of us think we’re going to see a decrease in hospitalization — and that’s only going to work in our best interest.”

If only we had these vaccines and antibodies this year. Right now, the RSV infection rate is rising, and hospitals emptied by the pandemic are struggling to make ends meet. Edwards said that many hospitals are increasing their staffing at this time of year, but that this is made more difficult by the shortage of medical professionals.

“Right, this season has been worse than most,” she said. “We don’t necessarily expect to have this bad season every year.”

“But as the staff shortage grows more severe across the country, we expect there will be fewer and smaller increases in the number of hospital staff,” she said.

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

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