It used to be relatively easy and straightforward to navigate the fall and winter respiratory disease season in the U.S.—get a flu shot. Then came COVID-19, and another vaccine was added to the mix.

Now, for the first time, there will be a third shot for some groups: a vaccine for respiratory syncytial virus (RSV), which causes respiratory disease that can be especially dangerous for infants and older people.

Here’s what experts say about who should be receiving which shots, and when.

Flu (the easy one)

The advice here is straightforward and the same as it’s always been: “Everybody should be getting a flu shot,” says Dr. Paul Offit, professor of pediatrics and director of the Vaccine Education Center at Children’s Hospital of Philadelphia, and a member of the U.S. Food and Drug Administration’s (FDA) expert vaccine committee.

Everybody, that is, who is eligible, which the Centers for Disease Control and Prevention (CDC) defines as anyone six months or older.

The flu vaccine’s efficacy varies widely from year to year, since health officials have to make their best guess about which strains of influenza will be circulating months ahead of time, in order to give the vaccine makers enough time to produce the shot. Historically, the seasonal flu shot has been40% to 60% effective in protecting people from getting sick with the flu, according to the CDC. Each year, about half of people who are eligible in the U.S. get vaccinated, although rates arelower among some groups, including among Black and Hispanic adults, for a variety of reasons, including inequitable access to health services, cultural barriers and skepticism about vaccines.

Even though most people feel they can shake off flu symptoms in a few days, it’s worth remembering that the viral infection can be dangerous and even deadly for those with chronic health conditions. According to the CDC, from 2010 to 2020, flu sent140,000 to 710,000 people to the hospital annually, most of whom were 65 years or older, and contributed to12,000 to 79,000 deaths each year.

The latest COVID-19 variants and vaccines

There will be an updated COVID-19 vaccine in mid-September, but U.S. health officials have not yet decided which specific SARS-CoV-2 strain the shot will target. InJune, the FDA’s independent panel of vaccine experts decided that the vaccine should be updated from its current version, which targets Omicron variants BA.4 and BA.5. The committee recommended moving to a new variant, from the XBB family, which was causing the majority of infections at the time—and, following guidance from the World Health Organization, the panel also advised that the updated vaccine target only one XBB strain, rather than two as the BA.4/5 shot did. The committee members suggested that vaccine manufacturers should focus on XBB.1.5, so Moderna, Pfizer and Novavax began developing and manufacturing those doses in time for fall.

Since then, newer variants have emerged, including EG.5, FL.1.5.1, and BA.2.86. But Moderna, Novavax, and Pfizer all say that early tests show their XBB shots can alsoneutralize the latest variants. In Moderna’s case, the data comes from early tests in people, while Novavax and Pfizer have so far only reported results in animal studies.

Once the FDA decides which strain the updated vaccine will contain, the CDC’s Advisory Committee for Immunization Practices will issue guidance on who should get it, and when. Not all experts believe everyone should receive the updated shot. Offit, for example, says most healthy people who have already had their primary series of the original vaccine and at least one booster dose, and likely also gotten infected at some point over the past few years, probably won’t need another booster. That’s based on data showing that the original vaccine combined with the first booster provided nearly as much protection as the updated booster targeting BA.4 and BA.5—and which Offit and others believe will continue to protect people from getting severely ill from the newest COVID-19 variants

The reason for that has to do with the T-cell immune response built up from those earlier versions of the shots. T-cells produce a long-lasting form of protection that’s designed to remember previous infections and mount stronger and quicker responses against things like viruses when people are exposed to them again. That’s because these cells focus on parts of the virus that are more conserved, or shared among different variants. And the recent variants are about 80% similar to the original strains, says Offit.

However, if scientists begin to see the virus mutating in a way that makes it harder for the T-cells of previously vaccinated people to recognize—or if data start to show that people who are hospitalized are more likely to be those who have not received the BA.4/5 booster, then that would make a case for giving the updated vaccine to more people.

For now, it’s likely that the updated vaccine will provide the most benefit to people who are most vulnerable to COVID-19 complications, such as the elderly, and those with chronic health conditions that weaken their immune systems.

RSV is the newest seasonal vaccine

For certain groups of people, there may be another shot in store for them this fall, since for the first time, there are FDA-approved ways to prevent RSV infections. RSV generally affects older people and infants, sending around 58,000 children under five to the hospital in the U.S. each year, and contributing to 14,000 deaths annually among those 65 or older.

The first of these shots is a vaccine, made by Pfizer, approved for people 60 years and older, and for pregnant people 32 to 36 weeks into their pregnancy. The second is a monoclonal antibody, called nirsevimab and made by Sanofi and AstraZeneca, which is approved for babies under eight months old. It’s not a vaccine, since it does not stimulate the babies’ immune systems to produce the antibodies like a vaccine does; instead, it simply injects these antibodies into their bloodstream in a single shot.

“We went from nothing to an abundance of riches,” says Dr. Cody Meissner, professor of pediatrics at Dartmouth Geisel School of Medicine and one of the FDA’s vaccine committee experts. “It’s really bringing us into a new era.” Meissner is also part of CDC’s vaccine group that is currently discussing how to guide physicians about using those new options.

That new world may come with quite a bit of confusion, however, at least at first. The question of whether to get vaccinated is pretty straightforward for people 60 or older—the shot can reduce the risk of hospitalization by around 80%.

The situation is more complicated for pregnant people and babies, however. The vaccine has been approved for pregnant people 32-36 weeks into the pregnancy, and the CDC is weighing whether to recommend it for all women in that group, or for certain women and their babies who might be more vulnerable to RSV when they are born, such as premature infants and those born with chronic lung conditions. The discussion was prompted by concerns about the potential risk of premature births associated with the shot that studies of the vaccine revealed.

In the Pfizer studies that led to FDA approval, among women who received the vaccine, there was a slightly higher percentage whogave birth early, before 37 weeks (5.7%), than among those who got a placebo, (4.7%). But the difference was not statistically significant. Still, that trend is potentially more concerning when coupled with the fact that another pharmaceutical company, GlaxoSmithKline, stopped developing a maternal RSV vaccine very similar to Pfizer’s after its studies found a statistically significant risk of preterm births associated with the shot. “One of two things could be true,” says Offit. “Either both have the same problem, and Pfizer hasn’t found it yet, or neither has a problem.” While there isn’t an obvious reason why the vaccine would contribute to premature delivery, the RSV protein targeted by the vaccine can trigger inflammatory reactions that could increase the risk for preterm birth.

The Pfizer study included women who were at least at 24 weeks of gestation. Because the risk of premature birth overall decreases the later into gestation, the FDA approved it for pregnant people beyond 32 weeks, when the risk of early delivery is lower.

The CDC’s working group is trying to figure out whether to recommend the vaccine for all expectant mothers, given this risk. “We are having more meetings about this than any other vaccine in my memory,” says Meissner. It’s unlikely, given the cost of the vaccine (up to $295) and the monoclonal antibody treatment, ($495 for the lowest dose for the smallest infants), that a pregnant woman would receive the vaccine and then have her baby get the antibody injection. “That’s duplicating responsibilities,” he says. “Like wearing suspenders and a belt. So we are in the process of sorting out, with weekly Zoom calls, how these would be used.”

Until then, Meissner says doctors need to discuss the potential risks with women, even if Pfizer’s data do not show a statistically significant danger of preterm births. “My personal opinion is a mother needs to be honestly told that this rate [of giving birth prematurely] is slightly higher with this vaccine,” he says. That conversation won’t be easy, especially for busy obstetricians who may not have the time to delve into the complicated nature of the data.

Over the next few months, health experts will be eager to see how effective the newest options are in curbing infections and, more importantly, reducing severe disease and keeping people out of the hospital. Pfizer says it plans to have adequate supply of its new RSV vaccine for both pregnant and older people in time for the fall (a spokesperson says vials labeled for older people can also be used for those who are pregnant until the new labeling is available).

But the updated and new vaccines, and the RSV antibody, will only have an impact if people have access to them. While the public health emergency for COVID-19 has ended, most insurers will continue to cover the updated COVID-19 vaccine, along with the flu shot. Certain Medicare plans will cover the RSV shot for older people, while the CDC has included both the maternal RSV vaccine and the antibody in its Vaccines for Children Program, which means that the government will provide these for families who are uninsured or cannot afford them.

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