To avoid a repeat of last winter’s “triple epidemic” of respiratory disease, Americans will be encouraged to roll up their sleeves not just for flu shots, but for two other vaccines, one of which is entirely new.
Federal health officials have already asked manufacturers to produce reformulated Covid vaccines for distribution later this year. Recently, the Centers for Disease Control and Prevention took it a step further by approving two new respiratory syncytial virus vaccines for older Americans.
All three vaccines – flu, Covid and RSV – could help reduce hospitalizations and deaths later this year. But there are uncertainties about how best to administer vaccines, who is most likely to benefit, and what the risks may be.
For older, immunocompromised Americans, the three vaccines are a “godsend,” said Dr. Ofer Levy, director of the precision vaccine program at Boston Children’s Hospital and adviser to the Food and Drug Administration.
“The number of seniors who die from viral infection every winter in our intensive care units, and also sometimes in the summer, is significant – it’s in the tens of thousands of individuals,” Dr. Levy said. “Each of these vaccines is a huge win.”
Still, it’s unclear how many Americans will opt for the shots. Some 71% of adults aged 65 and over got their flu shot last winter, but only around 43% chose to get the Covid shot.
The misery of the past winter can help change mentalities. The flu may have killed as many as 58,000, peaking in December, according to the CDC Covid killed around 50,000 between November and March.
RSV kills up to 10,000 people each year, most of them elderly. This year, infections peaked in November and resulted in about twice as many hospitalizations, including children, as in pre-pandemic years.
Only Covid and flu vaccines were available last fall. RSV vaccines for adults are new and in clinical trials have been shown to be very effective against infection of the lower respiratory tract, which includes the lungs.
In May, the FDA approved the first two versions, made by Pfizer and GSK, for seniors. CDC advisers recommend that Americans 60 and older get vaccinated in consultation with their doctor. (The Pfizer vaccine is also being evaluated for use in pregnant women as a way to protect newborn babies.)
Bundling all three vaccinations into one visit to a clinic or pharmacy will likely encourage more people to get vaccinated, Dr. Levy said. “Also, you want to get those shots ahead of the viral respiratory season in the winter,” he added.
But other scientists have been hesitant to endorse the idea, citing lack of data on safety and effectiveness when all three are given at the same time.
Sometimes vaccines work against each other when given at the same time. According to data presented to CDC advisers, RSV and influenza vaccines produced lower levels of antibodies when given at the same time than when given alone.
“I would say that, if possible, it might be good to spread them out,” said Dr. Camille Kotton, a physician at Massachusetts General Hospital and a member of the CDC’s scientific advisory board.
“I remain clinically concerned, particularly where the flu vaccine is not providing as much protection as we would like,” she said.
The vast majority of people at risk of illness and death from infections with these viruses are aged 75 and over. In this group, the benefits of each of the vaccines clearly outweigh the safety concerns, said Dr. Kotton and other experts.
According to the CDC, up to 85% of flu-related deaths in recent years have been in people age 65 and older. The agency recommends older people get the flu shot in high doses or with an adjuvant, an ingredient that can produce an immune response.
Hospitalizations and deaths from Covid are also occurring primarily among older Americans, and Covid boosters are now seen as beneficial primarily for the elderly and people with weakened immune systems.
In June, the FDA advised Pfizer-BioNTech, Moderna and Novavax to make Covid vaccines designed to target XBB.1.5, the Omicron variant that accounts for about 27% of cases. This variant seems to be on the decline, however, and a newer variant, XBB.1.16, is on the rise.
RSV is the leading cause of infant hospitalizations in the United States and a leading cause of death among young children in low- and middle-income countries. The virus was underestimated as a respiratory threat for adults until recently.
The virus can lead to up to 160,000 hospitalizations and 10,000 deaths among the elderly each year, according to the CDC — and those numbers are likely understated. For every million adults aged 65 and over who receive the vaccine, 25,000 outpatient visits, 2,500 hospitalizations and 130 deaths would be averted, according to an analysis presented to agency advisers.
For decades, RSV vaccines have proven difficult to design. A breakthrough in 2013 galvanized the efforts of several companies. In a recent trial, the GSK vaccine, which will be sold as Arexvy, retained much of its potency in the second year, and its effectiveness is being studied over an even longer period.
Pfizer is still evaluating the durability of its vaccine, which will be marketed as Abrysvo. If the vaccines remain effective for a long time, an injection of RSV may not be necessary every year.
The companies’ trials did not recruit enough people who were immunocompromised, medically frail, living in long-term care facilities, or aged 75 and older to assess effectiveness in these groups. They are also the Americans most vulnerable to RSV
Although influenza and other vaccines carry a small risk of the autoimmune disease, Guillain-Barré syndrome, these numbers are usually in the order of one or two cases per million. In evaluating new RSV vaccines, manufacturers have each reported three neurological cases, including Guillain-Barré syndrome, within 42 days of vaccination in a population of approximately 40,000 people.
Still, the trials weren’t large enough to determine whether these cases happened by chance or were caused by the vaccines. “This information really can’t be obtained before licensing and after referral and deployment,” said Dr. Helen Chu, a physician and immunologist at the University of Washington.
Influenza, Covid and RSV infections themselves pose a risk for Guillain-Barré syndrome and other neurological problems, so the risk-benefit balance still strongly favors vaccination, Dr Chu said.
Still, reports of adverse events related to RSV vaccines have made some CDC advisers reluctant to back them for people who aren’t at high risk of infection.
That’s part of why the scientific panel said anyone aged 60 and over ‘can’ choose to get vaccinated in consultation with a doctor, rather than issuing a blanket recommendation for all adults over 60. or even 65 years old.
The move risks deepening racial inequities regarding vaccination, some experts have said. Many people of color, often at a disproportionate risk of serious illness or death, do not have easy access to a health care provider who could help them weigh the risks and benefits of RSV vaccination.
The recommendation also requires GPs and other healthcare providers to weigh the risks and benefits, Dr Chu noted.
“It’s hard for the committee,she said, referring to the CDC’s expert panel. “It’s definitely going to be much, much more difficult for a GP”
The CDC’s recommendations ensure that most Americans won’t have to pay out of pocket for vaccines. This fall marks the first time that the distribution of Covid vaccines will not be managed by the federal government, but insurance companies will continue to cover the costs.
How much Pfizer and GSK will charge for the new RSV vaccines is still unclear. Pfizer said the price of its vaccine is still being negotiated, but could be between $180 and $270.
GSK doubled its original price of $148 two weeks before the scheduled meeting of CDC advisers, leaving agency staff little time to redo its cost-effectiveness analysis, according to a CDC scientist with knowledge of the matter. GSK has now opted for a range of $200 to $295.
GSK raised its price due to new data showing efficacy in a second season, said company spokeswoman Alison Hunt.
Ongoing research will likely provide more information about new RSV vaccines. In preliminary data, a second dose of the GSK vaccine did not increase antibody levels, which puzzled scientific advisers at last week’s meeting.
Pfizer is studying whether a second dose of its vaccine, given a year after the first, will boost immunity. These results are expected early next year. The companies are also studying whether immunocompromised people should receive a single dose or two doses given a month apart.
“We never have all the information we want,” said FDA adviser Dr. Levy.
“But one thing we know for sure is that every winter people lose loved ones, grandmothers, grandfathers to viruses, and now we have better tools. And we want to deploy them.