June 9, 2023 – After nearly 60 years of effort, vaccine protection against the potentially lethal respiratory infection respiratory syncytial virus, or RSV, is finally a reality.
The FDA approved two new RSV vaccines: GSK’s Arexvy on May 3, and Pfizer’s Abrysvo on May 31. Both approvals are for adults ages 60 and above, who are among the most vulnerable to the infection.
If the CDC recommends the vaccines – a decision that's expected after its Advisory Committee on Immunization Practices meets June 21 and gives its recommendation – both vaccines could be available by fall, ahead of the RSV season.
The new vaccines are “a wonderful advance,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University Medical Center in Nashville, and medical director of the National Foundation for Infectious Diseases.
Yet he and other experts wonder if Americans have so much “vaccine fatigue” that they will pass up the shot – especially since it is expected to be offered at the same time as the annual influenza vaccine and an updated COVID-19 booster.
Awareness about the disease itself is another issue that may thwart the vaccine effort, as even some doctors mistakenly think of RSV as solely a pediatric danger, other experts said.
RSV Danger for Older Adults, Children
RSV is a contagious virus, spread via virus droplets, direct contact with the virus, or touching a surface with the virus on it, causing lower respiratory infections. It can occur in all age groups but can be especially dangerous in older adults and children younger than 5. Symptoms may include a runny nose, coughing, sneezing, a decreased appetite, a fever, and wheezing.
The virus circulates seasonally, usually beginning in the fall and peaking in winter.
Often, the infection is mild and clears up, but it can turn serious, leading to more severe infections such as pneumonia.
Each year, 60,000 to 160,000 adults 65 and older are hospitalized for RSV, according to the CDC, and 6,000 to 10,000 deaths in that age group are blamed on the virus. Among children younger than 5 years, 58,000 to 80,000 are hospitalized each year with RSV; 100 to 300 die from it. What's more, 2.1 million outpatient visits among children younger than 5 involve RSV annually.
No specific treatment exists for RSV, but hospitalized patients may receive IV fluids and oxygen.
Effectiveness
The FDA’s approval of Arexvy, the vaccine from GSK (formerly GlaxoSmithKline), is based on clinical trial research studying a single dose given to people ages 60 and older. In the main phase III clinical trial, 12,500 people received Arexvy and 12,500 received a placebo.
The vaccine reduced the risk of getting RSV-associated lower respiratory tract disease by 82.6% and the risk of having a severe disease by 94.1%.
Leonard Friedland, MD, GSK’s vice president and director of scientific affairs and public health, vaccines, termed those results “exceptional” in an emailed response to questions.
Side effects reported by some patients most commonly involved pain where they got the shot, fatigue, muscle pain, a headache, and joint pain or stiffness. Atrial fibrillation, an abnormal heart rhythm, was reported in 10 people who got the vaccine and four who received the placebo.
Two other studies evaluated about 2,500 people receiving the vaccine. In a group receiving the RSV vaccine with an influenza vaccine, two people had a kind of inflammation affecting the brain and spinal cord, acute disseminated encephalomyelitis (ADEM). One died.
In another study, one person developed Guillain-Barre syndrome, a disorder that occurs when the immune system damages nerve cells, leading to muscle weakness and sometimes paralysis. The FDA is requiring the company to do a post-marketing study to investigate further the risks for Guillain-Barre syndrome and ADEM. GSK said it will also assess atrial fibrillation risks in a post-marketing study, voluntarily.
The FDA approved Pfizer’s Abrysvo based on the results of an ongoing clinical trial in which about 17,000 people got the vaccine and another 17,000 got a placebo, analyzing data from the first RSV season of the study.
The vaccine reduced the risk of RSV-related lower respiratory tract disease with two or more symptoms by 66.7% and three or more symptoms by 85.7%. It was 62% effective against RSV-associated acute respiratory illness, which can lead to hospitalization.
Some people in the study reported fatigue, a headache, pain where they got the shot, and muscle pain as the most common side effects. One person got Guillain-Barre syndrome; another got a variant form of it. Atrial fibrillation was reported by 10 people who got the vaccine and four who got a placebo.
The FDA is requiring Pfizer to do a post-marketing study on the risks of Guillain-Barre; the company said it will assess voluntarily the atrial fibrillation risk further as well.
Experts interviewed for this story said the vaccines are comparable in effectiveness and declined to recommend one over the other. No head-to-head studies of the two approved vaccines have been done.
How the Vaccines Work
The Pfizer and GSK vaccines target a protein, known as the F protein, on the surface of the virus. The protein changes shape; when it does so, it helps the virus fuse to cells in people, letting it infect the cell. But researchers have found a way to keep this protein in its pre-fusion state, so an immune response is triggered.
With this immune response, “the antibodies produced against the F protein interfere with the virus’ ability to fuse and infect cells, enabling the immune system to fight off the virus better,” said Ann Falsey, MD, a professor of medicine at the University of Rochester School of Medicine and co-director of the University of Rochester Medical Center’s Vaccine and Treatment Evaluation Unit.
“The Pfizer vaccine contains two versions of the F protein to cover both subtypes of the virus, known as RSV-A and RSV-B,” said Aaron Glatt, MD, chief of infectious diseases at Mount Sinai South Nassau, in New York, and a spokesperson for the Infectious Diseases Society of America.
“The GSK vaccine is based solely on the version of the protein found in RSV-A, but also contains an adjuvant, or a substance that is designed to boost the immune response to the virus,” he said.
This F protein, which can rapidly change its structure, is also one of the reasons it took so long to come up with a vaccine for RSV.
Next Stop: CDC Weighs In
The CDC’s Advisory Committee on Immunization Practices, an independent panel, will meet June 21 and recommend who should get the new vaccines.
The expectation, Schaffner said, is that the panel will recommend the vaccine for those 60 and over or for those 65 and older. The CDC is not bound to follow the ACIP’s recommendations but typically does so.
Who Should Get the RSV Vaccine?
The CDC recommendation will more clearly spell out the starting age, experts expect. “I hope they recommend it for adults over 60, because that’s the population the trials were done in,” said Falsey, a longtime researcher of respiratory viruses and vaccines, including other RSV vaccines.
Older adults should discuss their situation with their doctor when making the decision, experts said. “Not every 60- or 65-year-old should be running out to get this,” Glatt said, suggesting it should be an individual decision.
Age is one risk factor for RSV, he said, but having other conditions – such as heart or lung disease or a weakened immune system – also increases the risk.
As an example, Glatt said, he would likely tell a healthy 62-year-old triathlete with no heart disease that he would “probably not get much bang” for his buck by getting the vaccine. But, he said, he would recommend that a 75-year-old patient who recently had cardiac transplant surgery or who has COPD (chronic obstructive pulmonary disease) and on nasal oxygen should get it.
How concerning is the risk of Guillain-Barre, pending results from the ongoing study? “It remains an unknown, which is why I would stress giving it to people at higher risk rather than [to] all over 60,” Glatt said.
Frequency, Insurance, and Supply
The frequency of this vaccination is yet to be decided. More data is needed. Researchers are continuing to follow people in the trials to find the best interval.
The recently enacted Inflation Reduction Act got rid of copays for recommended vaccines under Medicare Part D. About 51 million people of the more than 65 million on Medicare have Part D plans.
If the CDC does end up recommending the vaccine, then commercial insurance will likely pay for it.
Reuters reports that the standalone cost for GSK's Arexvy is expected to be $120.
Both companies said they expect their supplies will meet the demand for the vaccine.
Hard Sell or Acceptance?
In a commentary on Medscape (WebMD's sister site for medical professionals), family doctor Kenneth W. Lin, MD, MPH, said health care workers should educate patients about the disease and the need for protection.
He expects hesitancy, writing: “Many of our patients won't have heard about it, may feel that they don't need it, or may decline it because of concerns about side effects, real or imagined.”
On the other hand, acceptance of the new RSV vaccine may be higher than some predict, Schaffner said. He cited the increased willingness of those ages 65 and older to get the bivalent COVID booster, compared to younger people. As of May 11, 2023, 43.3% of U.S. adults 65 and over had received that booster, according to the CDC, compared to about 20.5% of those ages 18 to 64.
The Long Haul to a Vaccine — and Recognition of RSV
RSV has “flown under the radar as an adult disease for so many years,” Falsey said. The general population as well as some doctors think of RSV as only a children’s disease. She calls it “the worst disease no one has heard of.”
In the past, she said, patients in the hospital with a viral illness who tested negative for influenza may very well have had RSV, but they may have not been tested for it.
While awareness is growing, Falsey said the level of it varies among health care providers.
“The infectious disease doctors understand it to be a problem, and the pulmonary doctors do,” she said, but an internist might not see RSV as a problem in many older adults.
RSV was discovered in 1956, according to the CDC. Vaccine development began in the 1960s, according to the World Health Organization, but the first vaccine was scrapped after two children died and others had severe lung inflammation after being vaccinated and becoming infected.
Next Goals: Infants, Children via Mothers
RSV protection for infants and children is the next challenge. One possible avenue, experts know, is to vaccinate pregnant women. Pfizer is seeking approval for a maternal vaccine meant to prevent RSV in infants from birth to 6 months by immunizing pregnant women.
In a clinical trial, about 3,600 pregnant women received the vaccine, and 3,600 others got the placebo. The vaccine was nearly 82% effective at preventing infection in the infants.
An FDA panel recommended the vaccine in May. While the agency is not required to accept the recommendations of its advisory panels, it often does, but the process could still take months. The FDA has given Pfizer a date in August, though, as a probable deadline for its decision.
Another FDA panel on Thursday unanimously recommended a new RSV medication for infants called nirsevimab. The drug company AstraZeneca said in a news release after the meeting that it's "the first preventive option specifically designed to protect the broad infant population through its first RSV season."
It's not by definition a vaccine but instead a monoclonal antibody (an antibody developed in a lab) that's given by a single-dose shot into the muscle, preferably in the child's thigh.
The FDA is expected to make a final decision on the drug by this fall, which would make it available in the U.S. ahead of the 2023-24 RSV season.
Other RSV vaccines for adults are still in late-stage clinical trials, one an mRNA vaccine (similar to some COVID vaccines) from Moderna, and another from Bavarian Nordic, the maker of the mpox vaccine.
RSV, Flu, COVID Shots at Same Time?
Could older adults get vaccines for the flu, RSV, and COVID all at once?
Spokespersons for GSK and Pfizer said based on their research, giving the RSV vaccine with the influenza vaccine is safe.
“There is currently no data on co-administration of Arexvy with other vaccines [besides the flu vaccine],” according to GSK’s Friedland.
As for getting two shots in one arm, “Health care professionals typically, when giving more than one vaccine at the same time, will do so with one vaccine in one arm, and the other vaccine in the other arm,” Friedland said.