Federal officials are hatching a three-pronged defense against another “triple pandemic.”

To prevent a repeat of last winter’s “triple epidemic” of respiratory illness, Americans will be encouraged to roll up their sleeves for not just the flu shot but two more vaccines, one of which is brand new.

Federal health officials have already required manufacturers to produce reformulated Covid vaccines to be distributed later this year. Recently, the Centers for Disease Control and Prevention went one step further, endorsing two new respiratory syncytial virus (RSV) vaccines for older Americans.

The three vaccines — influenza, Covid virus, and RSV — may help reduce hospitalizations and deaths later this year. But there are uncertainties about how the vaccines are best given, who is most likely to benefit, and what the risks might be.

For older and immunocompromised Americans, the three vaccines are a “godsend,” said Dr. Ofer Levy, director of the Precision Vaccine Program at Boston Children’s Hospital and an advisor to the Food and Drug Administration.

“The number of elderly people who die from viral infections each winter in our intensive care units, and sometimes in the summer as well, is significant — tens of thousands of individuals,” said Dr. Levy. “Each of these vaccines is a huge win.”

However, it is unclear how many Americans will pick the shots. About 71 percent of adults 65 and older got a flu shot last winter, but only about 43 percent chose to get a Covid booster.

The misery of last winter may help change minds. The flu might have caused it Up to 58,000 deathspeaking in December, and according to the CDC, Covid claimed nearly 50,000 lives between November and March.

RSV kills up to 10,000 people each year, most of them older. Infections peaked this year in November and resulted in About twice as many hospital admissionsincluding children, as in the pre-pandemic years.

The Covid and flu vaccine was only made available last fall. RSV vaccines for adults are new, and in clinical trials have shown to be highly effective against infections of the lower respiratory tract, which includes the lungs.

In May, the Food and Drug Administration approved the first two versions, made by Pfizer and GSK, for seniors. Advisers for the Centers for Disease Control and Prevention (CDC) recommend that Americans 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 newborns.)

Combining the three vaccinations into one visit to a clinic or pharmacy is likely to encourage more people to get immunized, Dr. Levy said. “In addition, you want to get these shots in the arms before the winter respiratory viral season,” he added.

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

Sometimes, vaccines work against each other when taken simultaneously. According to data provided to advisors for the Centers for Disease Control and Prevention, the RSV and influenza vaccines produced lower antibody levels when given at the same time than when either was given alone.

“I would say, when possible, it might be a good idea to make them public,” said Dr. Camille Cotton, a physician at Massachusetts General Hospital and a member of the Centers for Disease Control and Prevention’s Scientific Advisory Committee.

“I still worry clinically, especially when the flu vaccine doesn’t generate as much protection as we might like,” she said.

The vast majority of people at risk of illness and death after infection with these viruses are 75 years of age or older. Clearly, the benefit of each vaccine outweighs any safety concerns, said Dr. Cotton and other experts in that group.

up to 85 percent of Influenza related deaths In recent years they were among those 65 and older. According to the CDC, the agency recommends that older adults get a high-dose flu shot or a vaccine containing an adjuvant, an ingredient that can produce a stronger immune response.

Covid hospitalizations and deaths occur primarily in older Americans, and Covid boosters are now thought to be primarily beneficial for the elderly and people with compromised immune systems.

In June, the US Food and Drug Administration advised Pfizer-BioNTech, Moderna and Novavax to manufacture Covid shots designed to target XBB.1.5, the Omicron variant that represents approximately 27 percent of cases. However, this variant appears to be declining, and the most recent variant, XBB.1.16, is on an upward trend.

RSV is the main cause of Infants in the hospital In the United States, and Among the great killers of young children in low- and middle-income countries. The virus was not appreciated as a respiratory threat to adults until recently.

The virus may lead to up to 160,000 hospitalizations and 10,000 deaths among the elderly each year, according to CDC – These numbers are likely to be an underestimate. For every 1 million adults age 65 and over who get the vaccine, 25,000 outpatient visits, 2,500 hospitalizations and 130 deaths will be prevented, according to one analysis provided to the agency’s advisers.

For decades, vaccines against respiratory syncytial virus have proven difficult to design. The 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 effectiveness in the second yearand its effectiveness is under study for a longer period.

Pfizer is still assessing the viability of its vaccine, which will be marketed as Abrysvo. If the vaccines remain effective over a long period, the RSV shot may not be needed every year.

The companies’ trials did not enroll enough people who are immunocompromised, medically vulnerable, live in long-term care facilities, or are 75 or older to measure effectiveness in those groups. These are also the Americans most likely to be infected with RSV

Although influenza and other vaccines carry a small risk of the autoimmune disease Guillain-Barré syndrome, generally these numbers are in the order of one or two cases per million. In evaluating the new RSV vaccines, manufacturers reported three neurological conditions, 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. “This information can only really be obtained after authorization and after recommendation and enforcement,” said Dr. Helen Zhou, a physician and immunologist at the University of Washington.

Influenza, coronavirus and respiratory syncytial virus infections themselves pose a risk of Guillain-Barre syndrome and other neurological problems, said Dr. Chu, so the balance between risks and benefits still strongly favors vaccination.

However, reports of adverse events related to RSV vaccines have made some CDC advisors reluctant to support them for people who do not face a high risk of infection.

This is partly why the scientific panel said anyone 60 or older “may” choose to get the vaccine in consultation with a doctor, rather than issuing a blanket recommendation for all adults over 60 or even 65.

Some experts said the decision risks deepening racial inequality with regard to vaccination. Many people of color, who are often at disproportionate risk of severe illness or death, do not have easy access to a healthcare provider who might help them assess the risks and benefits of RSV vaccination.

Dr Chu noted that the recommendation also places the onus on general practitioners and other healthcare providers to assess the risks and benefits.

“It’s hard for the commissionAndshe said, referring to the CDC’s expert panel. “It would certainly be much more difficult for a general practitioner.”

The Centers for Disease Control and Prevention’s recommendations ensure that most Americans will not have to pay out of pocket for vaccines. This fall marks the first time the federal government will not manage distribution of Covid vaccines, but insurance companies will continue to cover the costs.

How much Pfizer and GSK will charge for the new RSV vaccines remains unclear. Pfizer said the price of its vaccine is still being negotiated, but it could fall between $180 and $270.

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

Allison Hunt, a spokeswoman for the company, said GSK raised its price because of new data showing its effectiveness in the second season.

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

Pfizer is investigating whether a second dose of its vaccine, given one year after the first, would boost immunity. These results are expected early next year. The companies are also looking into whether people who are immunocompromised should get one or two doses one month apart.

“We never have all the information we want,” said Dr. Levy, an advisor to the Food and Drug Administration.

“But the one thing we know for sure is that every winter people lose loved ones, grandparents, and grandparents to viruses, and now we have better tools. And we want to spread it.”