Federal officials develop a three-pronged defense against another ‘triple disease’

To prevent a repeat of last winter’s “triple pandemic” of respiratory illnesses, Americans are being encouraged to roll up their sleeves not only for the flu shot but also for two other vaccines, one of which is entirely new.

Federal health officials have already urged manufacturers to produce reformulated Covid vaccines to be distributed later this year. Recently, the Centers for Disease Control and Prevention took another step, recommending two new respiratory syncytial virus vaccines for older Americans.

The three vaccines – flu, Covid and RSV – could help reduce hospitalizations and deaths later this year. However, there are uncertainties about how best to administer the vaccines, 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 consultant to the Food and Drug Administration.

“The number of elderly people dying from a viral infection in our intensive care units every winter and sometimes in the summer is large — in the tens of thousands,” said Dr. Levy. “Each of these vaccines is a huge asset.”

Still, it’s unclear how many Americans will choose to get vaccinated. About 71 percent of adults aged 65 and over received a flu shot last winter, but only about 43 percent opted for the Covid booster shot.

Last winter’s misery might help change minds. According to the CDC, the flu may have caused as many as 58,000 deaths and peaked in December. Between November and March, Covid claimed around 50,000 lives.

RSV kills up to 10,000 people each year, most of whom are elderly. Infections peaked in November this year, prompting about twice the number of hospitalizations, including children, as in the pre-pandemic years.

Last fall, only the Covid and flu vaccines were available. The adult RSV vaccines are new and clinical trials have shown them to be highly effective against infections of the lower respiratory tract, which includes the lungs.

In May, the FDA approved the first two versions of Pfizer and GSK for older adults. CDC advisers recommend Americans age 60 and older to get vaccinated in consultation with their doctors. (Pfizer’s vaccine is also being evaluated for use in pregnant women as a way to protect newborns.)

Bundling all three vaccines into a single visit to a clinic or pharmacy will likely encourage more people to get vaccinated, said Dr. Levy. “Also, you want to get those shots ahead of the winter viral respiratory season,” he added.

However, other scientists have been reluctant to support the idea, citing the lack of data on safety and effectiveness when all three are administered at the same time.

Sometimes vaccines work against each other when given together. According to the data provided to the CDC consultants, the RSV and influenza vaccines resulted in lower levels of antibodies when given together than when given alone.

“I would say if possible it would make sense to distribute them,” said Dr. Camille Kotton, a physician at Massachusetts General Hospital and a member of the CDC Scientific Advisory Board.

“I remain clinically concerned, especially since the flu vaccine is not providing the protection that we would like,” she said.

The vast majority of people who are at risk of becoming ill or dying from infection with these viruses are 75 years and older. In this group, the benefits of each individual vaccine clearly outweigh any safety concerns, said Drs. Kotton and other experts.

According to the CDC, up to 85 percent of flu-related deaths in recent years have been in people ages 65 and older. 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.

Also, hospitalizations and deaths from Covid are particularly prevalent among the oldest Americans, and it is now believed that Covid boosters are particularly beneficial for older adults and those with compromised immune systems.

In June, the FDA advised Pfizer-BioNTech, Moderna and Novavax to manufacture Covid vaccines targeting XBB.1.5, the Omicron variant that accounts for about 27 percent of cases. However, this variant seems to be on the decline and a newer variant, XBB.1.16, is on the rise.

RSV is the leading cause of infant hospitalizations in the United States and is a leading cause of death in young children in low- and middle-income countries. Until recently, the virus was underestimated as a respiratory hazard for adults.

According to the CDC, the virus can cause as many as 160,000 hospitalizations and 10,000 deaths in older adults each year — and those numbers are likely to be underestimated. For every million adults aged 65 and over who receive the vaccine, 25,000 outpatient visits, 2,500 hospitalizations and 130 deaths could be prevented, according to an analysis presented to the agency’s advisers.

For decades, developing vaccines against RSV has proved difficult. A breakthrough in 2013 sparked the efforts of several companies. In a recent trial, the GSK vaccine, to be sold as Arexvy, retained much of its effectiveness into year two, and its effectiveness is being studied over an even longer period.

Pfizer is still evaluating the shelf life of its vaccine, to be marketed under the Abrysvo name. If the vaccines remain effective over a long period of time, RSV vaccination may not be necessary every year.

The companies’ studies did not include enough people who were immunocompromised, medically compromised, living in long-term care facilities, or aged 75 and over to assess effectiveness in these groups. These are also the Americans most affected by RSV

Although influenza and other vaccines carry a low risk of the autoimmune disease Guillain-Barré syndrome, these numbers are generally on the order of one to 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.

Still, the studies weren’t large enough to determine whether these cases were accidental or caused by the vaccines. “This information can really only be obtained after approval, endorsement and implementation,” said Dr. Helen Chu, 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 benefit-risk balance still strongly supports vaccination, said Dr. Chu.

Still, the reports of adverse events associated with the RSV vaccines have caused some CDC advisors to be reluctant to endorse them for people who are not at high risk of infection.

That’s partly why the scientific panel said that anyone over the age of 60 “can choose to get vaccinated in consultation with a doctor,” rather than making a blanket recommendation for all adults over 60 or even 65.

This decision risks widening racial inequalities when it comes to vaccinations, some experts have said. Many people of color, who are often at disproportionate risk of serious illness or death, do not have easy access to a healthcare provider who could help them weigh the risks and benefits of RSV vaccination.

The recommendation also places a duty on general practitioners and other healthcare providers to weigh the risks and benefits, noted Dr. Chu.

“It is difficult for the committee,she said, referring to the CDC’s panel of experts. “It will certainly be much, much more difficult for a general practitioner”

The CDC’s recommendations ensure that most Americans won’t have to pay for the vaccines out of their own pocket. This autumn, for the first time, the distribution of Covid vaccines will not be managed by the federal government, but the costs will continue to be covered by insurance companies.

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 range anywhere from $180 to $270.

According to a CDC scientist familiar with the matter, GSK doubled its original price of $148 two weeks before CDC advisors were scheduled to meet, giving agency staff little time to revise their cost-effectiveness analysis. GSK has now settled on a range of $200 to $295.

GSK has increased its price because new data shows efficacy in a second season, said Alison Hunt, a company spokeswoman.

Ongoing research should provide more information on the new RSV vaccines. According to preliminary data, a second dose of the GSK vaccine did not raise antibody levels, which confused 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. Those results are expected sometime early next year. The companies are also investigating whether people with compromised immune systems should be given a single dose or two doses a month apart.

“We never have all the information we want,” said Dr. Levy, the FDA advisor.

“But one thing we do know for sure is that every winter people lose loved ones, grandmothers and grandfathers to the viruses, and now we have better tools. And we want to use them.”

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