It took 60 years, but RSV vaccines are just around the corner — and could make a big difference

First RSV vaccine approved this month; more treatments on the horizon. You might have seen the news earlier this month: the U.S. has approved the first vaccine for respiratory syncytial virus (RSV), for use in adults age 60 and older.

One dose of the vaccine Arexvy, from drugmaker GSK, was found to be nearly 83 per cent effective at preventing RSV lung infections in a study published in The New England Journal of Medicine.

It has taken decades of research to get to this point. During a disastrous clinical trial for a potential RSV vaccine for children in the 1960s, 80 per cent of children given the shot were hospitalized and two toddlers died.

“The last 50 years have been spent in terms of understanding what caused that, how did the vaccine fail so spectacularly,” Sabina Vohra-Miller, founder of the website Unambiguous Science, told Dr. Brian Goldman,The Dose.

Once they’ve cleared all regulatory hurdles in Canada, the newly approved GSK vaccine, as well as other potential treatments to protect infants, could make a monumental difference in the number of people being hospitalized and dying from RSV, infectious disease and public health experts say.

RSV is a common but highly contagious virus that appears like a common cold for most people.

“But in younger people and older people, and in some immunocompromised people, it can actually cause lower respiratory tract infections,” said Vohra-Miller, who has a master’s of pharmacology and is a student in the doctor of public health program at the University of Toronto.

In those more vulnerable populations, RSV can cause bronchiolitis — the inflammation of the small airways in the lung — or pneumonia, say experts.

In children under five, RSV causes 100 to 300 deaths and up to 80,000 hospitalizations a year in the U.S.

Experts say cases of RSV are likely undercounted in Canada, so data is not accurate. But the virus is typically the leading cause of hospitalizations in children under one year of age in this country, said Dr. Jesse Papenburg, a pediatric infectious disease specialist and medical microbiologist at the McGill University Health Centre.

“The peak incidence of RSV hospitalizations is around two months of age. It’s really those youngest kids that are most at risk,” said Papenburg.

Babies have smaller lungs with smaller airways, he said, and the muscles of their chest wall are not as strong.
Last winter was a particularly bad season for RSV, said Papenburg.

“Uniformly across Canada, what was seen was an early and very intense RSV season,” he said.

“This was a real challenge for the pediatric health-care system.”

RSV can also be serious in older people. In the U.S., between 6,000 and 10,000 adults age 65 and older die each year from RSV, and there are between 60,000 and 160,000 hospitalizations.

It took longer for the disease to be recognized as a threat in the older population, said Papenburg, because doctors once thought RSV was only a problem for young children.

GSK’s vaccine for RSV was submitted to Health Canada for review in November 2022. It did not receive priority review, which means the agency has 12 months to decide whether to approve it.

The vaccine targets a protein subunit found on the surface of the RSV virus, and also contains an ingredient called an adjuvant to stimulate a stronger immune response.

The decades of work behind the vaccine are a win for research, said Fiona Brinkman, an infectious disease researcher at Simon Fraser University.

“It’s really great to see this kind of structural biology, that knowing how proteins are structured and how they change was able to lead to this discovery which then resulted in this vaccine,” said Brinkman.

During the clinical trial, reactions to the vaccine were mild and typical of other vaccinations, including pain at the injection site, fatigue, joint stiffness and headaches.

There was one reported case of Guillain-Barré syndrome, a rare but serious condition that can cause paralysis that is usually temporary.

The U.S. Food and Drug Administration (FDA), which approved the vaccine, said it has required GSK to continue studying whether that case was linked to the vaccine.
In a process called passive immunity, the pregnant person develops antibodies against the vaccine and transfers them to the baby through the placenta.

“Young babies do not really have a robust immune system. It’s not mature enough to actually make protective antibodies themselves in response to a vaccine,” said Vohra-Miller.

The best way to protect young babies from RSV is to transfer those antibodies to them while they’re still in the womb, she said.

Pfizer’s clinical trials showed the vaccine to be 82 per cent effective in preventing severe RSV infections in the first three months of the baby’s life, and nearly 70 per cent effective for the first six months.

In April, Health Canada approved a monoclonal antibody RSV treatment for use in infants during their first RSV season, made by AstraZeneca and Sanofi.

Infants would receive this type of antibody treatment through injection, but unlike a vaccine, it is not an active immunization.

“These are antibodies that will neutralize the pathogen, hopefully, before they cause an infection, or certainly before it causes a severe infection,” said Papenburg.

It is still unknown whether the treatment, called nirsevimab, would be recommended for all infants, or only those at risk of severe illness.

Drug to help prevent serious RSV illness in babies approved by Health Canada
That decision may depend on the price, said Papenburg.

“There are going to have to be economic analyses to see whether or not giving it to all infants as opposed to targeting high-risk infants will make sense,” he said.

The Canadian Agency for Drugs and Technology in Health (CADTH) is currently reviewing its cost-effectiveness. Once that review is finished, it will be sent to the National Advisory Committee on Immunization for recommendations.

Health Canada said that pending CADTH’s recommendations, it expects nirsevimab to be available for limited use during next fall and winter’s respiratory season.

There are still a lot of questions about both the Pfizer vaccine and the monoclonal antibody treatment, said Papenburg.

But he said if nirsevimab becomes available to all infants, “it would be a notable difference in the field and on the hospital ward and in the ICUs. It would be really major.”

“I don’t think it’s hyperbole to say it would be a game changer in pediatrics.”

Those disastrous clinical trials in the 1960s used an inactivated virus vaccine, an approach that backfired.

“The antibodies were not binding strongly enough to the inactivated virus to produce a really good protective immune response,” said Vohra-Miller.

“Instead, the antibodies were sort of dragging the dead virus with them wherever they went and that ended up triggering this massive attack by the entire immune system.”

How new treatments could quiet the ‘perfect storm’ of respiratory viruses
Experts say the results of that trial set RSV vaccine research back. But it’s also taken a long time to figure out the basic biology of an effective vaccine, said Brinkman.

“One of the biggest barriers was really needing the basic research to appreciate the biology of what was going on,” she said, “then [to] be able to develop a vaccine that was more appropriate that reflected that biology.”

Brinkman has had a vested interest in the development of a vaccine for RSV since she was a student in the 1980s, working in a Toronto lab that was studying potential vaccines.

“To see this actually happening now, so many decades later, is just wonderful.”

Other vaccines and treatments to come
The GSK vaccine for older adults isn’t the only potential RSV treatment on the horizon — Pfizer, Moderna and others are also developing their own RSV vaccines.

Pfizer is seeking approval in the U.S. and Canada for its vaccine in both adults age 60 and over and in pregnant people to protect newborns from the virus.

On Thursday, an FDA advisory panel said it supported approving Pfizer’s maternal vaccine to prevent severe illness in infants up to three months of age. The U.S. regulator does not have to follow the committee’s advice, although it often does.

Health Canada accepted Pfizer’s vaccine for review in April. If it’s approved, Papenburg said he expects we’ll see the vaccine available for us in Canada during the 2024/25 RSV season.