The new vaccines that protect older adults against respiratory syncytial virus, or RSV, may be linked to a small increased risk of developing Guillain-Barré syndrome, new data from the Centers for Disease Control and Prevention and the Food and Drug Administration suggest.
At a meeting Thursday of the Advisory Committee on Immunization Practices, vaccine safety experts from the two agencies presented data that showed what appears to be an elevated rate of GBS, as the condition is called, among people who got the Pfizer vaccine, although there were also cases detected among people who got the GSK product.
But the experts cautioned that it is too early to determine if there is a true increased risk of developing GBS after RSV vaccination, or to quantify the size of that risk, if it exists.
“We’re still in the early uptake phase of these new RSV vaccines,” Tom Shimabukuro, the former director of the CDC’s immunization safety office, told STAT in an interview after the meeting. Shimabukuro, who recently took a job as deputy director of the CDC’s influenza division, presented the GBS data to the ACIP meeting.
“Some of these data and findings are based on small numbers of cases and relatively small numbers of doses administered,” he said in the interview. “And due to uncertainties and limitations, based on these early data we can’t establish if there is an increased risk for GBS after RSV vaccination in these individuals 60 and older.”
Shimabukuro said the CDC would begin a more in-depth analysis using a different vaccine safety database in March. “Better risk estimates will be forthcoming in the coming weeks and months,” he said.
GBS is a neurological condition involving muscle weakness and sometimes paralysis. Most people fully recover over time, but some sustain permanent nerve damage. About two-thirds of people who are diagnosed with GBS develop the condition shortly after infection with a virus or a bacterium that causes diarrhea or a respiratory illness. GBS is more common in people aged 50 and older.
Some vaccines appear to increase the risk that a recipient will develop GBS. But teasing out whether there is a true link between a vaccine and GBS can be tricky. And in some cases, even if there is an increased risk of GBS following vaccination, that information has to be assessed in a broader context. For example, while it is thought that there is a small increased risk of developing GBS after flu vaccination — among 1 million people who get vaccinated, there may be one or two more cases than one would normally see in a similarly sized group of unvaccinated people — it’s known that contracting flu also increases the risk of developing GBS.
There have been concerns the new RSV vaccines, which were first brought to market last fall, might carry an increased risk of GBS after three cases were detected among people in the vaccine arms of the clinical trials Pfizer and GSK conducted to persuade the FDA to license the products.
The Pfizer vaccine is sold under the brand name Abrysvo while the GSK vaccine is sold as Arexvy.
Vaccine safety analysts at both the CDC and the FDA have been monitoring vaccine safety databases — primarily one known as the Vaccine Adverse Events Reporting System, or VAERS — looking for safety signals following the initial rollout of the RSV vaccines.
The VAERS database is where doctors and the pharmaceutical companies are supposed to report health events that happen in the hours or days after a person receives a vaccine. The data there cannot establish a cause-and-effect relationship between a vaccination and a health problem, but they can serve as an early warning signal.
By mid-February, CDC analysts had identified and verified 23 cases of GBS among the roughly 9.5 million people who have been vaccinated with one of the two vaccines. Fifteen of those were among people who got the Pfizer vaccine and eight were among people who received the GSK jab. Complicating the issue: 14 of the cases involved people who had received the RSV vaccine at the same time as another vaccine — a range of vaccines that included a variety of brands of flu shots and Covid-19 vaccines, as well as shingles vaccine, tetanus-diphtheria and pertussis vaccine, and a rabies shot.
In the 21 days after vaccination, the rate of GBS cases among recipients of the Pfizer vaccine was 4.6 per 1 million doses of vaccine administered. Among GSK recipients, the rate was 1.1 per 1 million. The expected background rate — the rate at which GBS occurs among people who get vaccinated with vaccines that don’t elevate one’s risk of developing GBS — is 2.0 cases per 1 million doses in the 21 days after a vaccination, Shimabukuro told the committee.
Reema Mehta, Pfizer’s vice president and head of risk assessment and management for worldwide safety, told the ACIP the company believes its vaccine is safe, but is conducting four post-marketing safety studies looking for GBS among recipients. “We will continue to share our findings with CDC, FDA, and other stakeholders as they become available,” she said.
In an email, GSK spokeswoman Alison Hunt noted that the CDC analysis did not suggest there was an elevated rate of GBS among people who had received the company’s RSV vaccine. Hunt said GSK is in the process of designing a study to evaluate the risk of GBS after receipt of Arexvy.
CDC vaccine experts told the ACIP that a risk-benefit analysis the agency conducted continues to support use of the vaccines in people aged 60 and older, because of the burden of RSV disease in that population. For every 1 million doses of RSV vaccine given, between 2,400 and 2,700 RSV hospitalizations, 450 to 520 intensive care unit admissions, and 120 to 140 deaths are averted, the agency estimated.
This signal comes at a time when GSK has indicated it hopes to persuade the FDA to expand the license for its RSV vaccine by lowering the age of people eligible to receive the shot to include people aged 50 to 59 who have health conditions that put them at risk of becoming severely ill if they contract RSV.
It also comes as ACIP’s RSV work group — a subcommittee of members, CDC staff, and outside experts — is mulling whether the CDC’s recommendation on who should get an RSV vaccine should change. The current policy, approved last fall, recommends the vaccine for people 60 and older if a health care provider believes vaccination would be beneficial. That recommendation — called shared decision-making — has confused physicians and some would-be recipients, and has probably depressed uptake of the vaccine, survey data suggest.
Amadea Britton, a CDC expert who is one of the leads of the RSV work group, said the group is considering changing that recommendation so that there would be a universal recommendation for some adults, perhaps people aged 75 and older. That would be the equivalent of CDC declaring, “These people should all get vaccinated.” In that scenario, the recommendation for people younger than that group would be based on individual risk, so would still require a recommendation from a health care provider.
Correction: An earlier version of this story misstated the risk of developing GBS after flu vaccination.