To prevent a repeat of last winter’s “triple epidemic” of respiratory illnesses, Americans will be encouraged to roll up their sleeves not just for flu shots but for two other vaccines, one of them brand new.
Federal health officials have already asked manufacturers to produce reformulated Covid vaccines to be distributed later this year. Recently, the Centers for Disease Control and Prevention took an additional step, endorsing two new vaccines against respiratory syncytial virus for older Americans.
The three shots — flu, Covid and RSV — may help reduce hospitalizations and deaths later this year. But there are uncertainties about how the vaccines are best administered, who is most likely to benefit, and what the risks may be.
For older and immunocompromised Americans, all three vaccines are “a godsend,” said Dr. Ofer Levy, director of the precision vaccines program at Boston Children’s Hospital and an adviser to the Food and Drug Administration.
“The number of elderly people who die from a viral infection every winter in our intensive care units, and also sometimes in the summer, is large – it is in the tens of thousands of individuals,” said Dr. Levy. “Each of these vaccines is a huge win.”
However, it is unclear how many Americans will be selected for the shots. About 71 percent of adults age 65 and older got a flu shot last winter, but only about 43 percent opted to get the Covid boost.
The misery of last winter can help change minds. The flu may have led to up to 58,000 deathspeaking in December, according to the CDC Covid claimed about 50,000 lives between November and March.
RSV kills up to 10,000 people each year, most of them elderly. Infections this year peaked in November and resulted approximately twice as many hospitalizationsincluding children, as in pre-pandemic years.
Only the Covid and flu vaccines were available last fall. The RSV vaccines for adults are new, and in clinical trials have proven 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 older adults. CDC advisors recommend that Americans age 60 and older get the shot in consultation with their doctors. (The Pfizer vaccine is also being evaluated for use in pregnant women as a way to protect newborn babies.)
Combining all three inoculations into a single visit to a clinic or pharmacy is likely to encourage more people to get immunized, Dr. Levy said. “Also, you want to get these shots in arms before the viral respiratory season in the winter,” he added.
But other scientists have been hesitant to endorse the idea, citing the lack of data on safety and efficacy when all three are given at the same time.
Sometimes, vaccines work against each other when administered at the same time. According to data presented to CDC consultants, the RSV and flu vaccines produced lower levels of antibodies when given at the same time than when both were given alone.
“I would say, when 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 panel.
“I remain clinically concerned, especially where influenza vaccine does not generate 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 those 75 and older. In that group, the benefit of each of the vaccines clearly outweighs any safety concerns, Dr. Kotton and other experts said.
Up to 85 percent of flu-related deaths in recent years have been among those age 65 and older, according to the CDC The agency recommends that older adults get a high-dose flu vaccine or one with an adjuvant, an ingredient that can produce a stronger immune response.
Hospitalizations and deaths from Covid also occur mainly in the oldest Americans, and Covid boosters are now thought to be useful mainly for older adults and people with weakened immune systems.
In June, the FDA advised Pfizer-BioNTech, Moderna and Novavax to manufacture Covid shots designed to target XBB.1.5, the Omicron variant that is responsible for approximately 27 percent of cases. That variant seems to be retiring, however, and a newer variant, XBB.1.16 is on the rise.
RSV is the main cause of children’s hospitals in the United States, and among the main murderers of young children in low and middle income countries. The virus was underestimated as a respiratory threat to adults until recently.
The virus can lead to up to 160,000 hospitalizations and 10,000 deaths among older adults each year, according to the CDC – and those numbers are likely to be underestimated. For every million adults age 65 and older who receive the vaccine, 25,000 outpatient visits, 2,500 hospitalizations and 130 deaths would be prevented, according to one analysis presented to the agency’s consultants.
For decades, RSV vaccines have proven difficult to design. Success in 2013 galvanized the efforts of several companies. In a recent test, the GSK vaccine, to be sold as Arexvy, retained much of its potency into the second yearand its effectiveness is being studied for 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 RSV shot may not be needed every year.
The companies’ trials did not enroll enough people who were immunocompromised, medically frail, live in long-term care facilities, or were 75 and older to evaluate effectiveness in those groups. These are also the Americans most vulnerable to RSV
Although influenza and other vaccines carry a small risk of the autoimmune disease Guillain-Barré syndrome, those numbers are generally on the order of one or two cases per million. When evaluating the new RSV vaccines, the manufacturers each reported three neurological cases, including Guillain-Barré syndrome, within 42 days of vaccination in a population of about 40,000 people.
However, the trials were not large enough to determine whether these cases occurred by chance or were caused by the vaccines. “That information can’t really be obtained until after licensure and after recommendation and launch,” said Dr. Helen Chu, a physician and immunologist at the University of Washington.
Influenza, Covid and RSV infections themselves pose a risk of Guillain-Barré syndrome and other neurological problems, so the risk-benefit balance still strongly favors vaccination, Dr. Chu said.
However, the reports of adverse events related to the RSV vaccines have made some CDC advisors reluctant to support them for people who do not face high risks of the infection.
That’s partly why the scientific panel said that anyone 60 or older “can” choose to get the vaccine in consultation with a doctor, rather than making a general recommendation for all adults over 60 or even 65.
That decision risks deepening racial disparities in vaccination coverage, some experts said. Many people of color, often at disproportionate risk of severe 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 puts the onus on general practitioners and other health care providers to weigh the risks and benefits, Dr. Chu noted.
“It’s difficult for the committee,” she said, referring to the CDC’s expert panel. “It will certainly be much, much more difficult for a doctor”
The CDC’s recommendations ensure that most Americans will not have to pay out-of-pocket for the vaccines. This fall is 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 pay for the new RSV vaccines is still unclear. Pfizer said the price of its vaccine is still being negotiated, but may fall between $180 and $270.
GSK doubled its initial price of $148 two weeks before the CDC advisers were scheduled to meet, giving agency staff little time to redo its cost-effectiveness analysis, according to one CDC scientist with knowledge of the matter. GSK has now settled on a range of $200 to $295.
GSK raised its price because of the new data showing performance going into the second season, said Alison Hunt, a spokeswoman for the company.
Ongoing research is likely to provide more information about the new RSV vaccines. In preliminary data, a second dose of the GSK vaccine did not increase antibody levels, which puzzled the scientific advisers at last week’s meeting.
Pfizer is investigating whether a second dose of its vaccine, given a year after the first, will boost immunity. Those results are expected some time early next year. The companies are also studying whether people who are immunocompromised should receive a single dose or two doses given one month apart.
“We never have all the information we want,” said Dr. Levy, the FDA adviser.
“But one thing we know for sure is that every winter people lose loved ones, grandmothers, grandfathers to the viruses, and now we have better tools. And we want to deploy them.”