Federal officials hatch a 3-pronged defense against another ‘tripledemic’

To prevent a repeat of last winter’s “tripledemic” 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 entirely new.

Federal health officials have already asked manufacturers to produce reformulated COVID-19 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 to 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 elders who die of viral infection every winter in our intensive care units, and also sometimes in the summer, is large — it’s in the tens of thousands of individuals,” Levy said. “Each of these vaccines is a huge win.”

Yet it’s unclear how many Americans will opt for the shots. Some 71% of adults ages 65 and older got a flu shot this past winter, but only about 43% chose to get the COVID booster.

The misery of the past winter may help change minds. The flu may have led to as many as 58,000 deaths, peaking in December, according to the CDC. COVID claimed roughly 50,000 lives between November and March.

RSV kills up to 10,000 people each year, most of them older. Infections this year peaked in November and resulted in about twice as many hospitalizations, including children, as in prepandemic years.

Only the COVID and flu vaccines were available last fall. The RSV vaccines for adults are new, and in clinical trials proved to be highly 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. The CDC’s advisers 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 infants.)

Bundling all three inoculations into a single visit to a clinic or pharmacy is likely to encourage more people to get immunized, Levy said. “Plus, you want to get these shots in arms before the viral respiratory season in the winter,” he added.

But other scientists hesitated to endorse the idea, citing the paucity of data on safety and effectiveness when all three are given at the same time.

Sometimes, vaccines work against one another when administered simultaneously. According to data presented to the CDC’s advisers, the RSV and flu vaccines produced lower levels of antibodies when given at the same time than when either was 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 scientific advisory panel.

“I remain clinically concerned, especially where influenza vaccine doesn’t engender as much protection as we might like,” she said.

The vast majority of people at risk for illness and death following infections with these viruses are those 75 and older. In that group, the benefit from each of the vaccines clearly outweighs any safety concerns, Kotton and other experts said.

Up to 85% of flu-related deaths in recent years were 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 primarily in the oldest Americans, and COVID boosters are now thought to be beneficial primarily 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 accounts for roughly 27% of cases. That variant seems to be receding, however, and a newer variant, XBB.1.16, is on the upswing.

RSV is the leading cause of infant hospitalizations in the United States, and among the top killers of young children in low- and middle-income countries. The virus was underappreciated as a respiratory threat to adults until recently.

The virus may lead to as many as 160,000 hospitalizations and 10,000 deaths among older adults each year, according to the CDC — and those numbers are likely to be underestimates. For every one million adults age 65 and older who get the vaccine, 25,000 outpatient visits, 2,500 hospitalizations and 130 deaths would be prevented, according to one analysis presented to the agency’s advisers.

For decades, vaccines against RSV proved challenging to design. A breakthrough in 2013 galvanized efforts by several companies. In a recent trial, the GSK vaccine, to be sold as Arexvy, retained much of its potency into the second year, and its efficacy 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 over a long time, an RSV shot may be not be needed every year.

The CDC’s recommendations ensure that most Americans will not have to pay out of pocket for the 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 was still being negotiated, but might fall between $180 and $270.

GSK doubled its initial price of $148 two weeks before the CDC advisers were scheduled to meet, giving the agency staff little time to redo its cost-effectiveness analysis, according to one CDC scientist with knowledge of the matter. GSK now has settled on a range of $200 to $295.

GSK raised its price because of the new data showing effectiveness into a second season, said Alison Hunt, a spokesperson for the company.

Ongoing research is likely to provide more information on the new RSV vaccines. In preliminary data, a second dose of the GSK vaccine did not boost antibody levels, which puzzled the science advisers at last week’s meeting.

Pfizer is investigating whether a second dose of its vaccine, given one 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 get a single dose or two doses given one month apart.

“We never have all the information we want,” said 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.”