Second Covid-19 vaccine boosters, explained

You counted the days until your vaccine appointment, posted a selfie with a bandage on your arm, and diligently came back weeks later for the follow-up shot, already making plans to enjoy hot vax summer. But new Covid-19 variants stepped out of the shadows, and health officials recommended that everyone get a booster dose. You got yours and thought you were done. Then omicron spawned its own subvariants that started infecting people even if they already had Covid-19 and their boosters.

So, do you need another Covid-19 shot?

For many people, right now, the unsatisfactory answer is “it depends.”

Last week, the US government announced it was buying 66 million doses of Moderna’s variant-specific Covid-19 vaccine booster, adding to the 105 million doses of reformulated vaccines purchased from Pfizer earlier. The companies say they will likely be available in October and November.

“We must stay vigilant in our fight against COVID-19 and continue to expand Americans’ access to the best vaccines and treatments,” wrote Health and Human Services Secretary Xavier Becerra in a statement. “As we look to the fall and winter, we’re doing just that.”

But federal officials also said that they weren’t yet changing the eligibility guidelines for a fourth dose. Currently, they’re recommended only for people over the age of 50 and people who are immunocompromised. Everyone else will likely have to wait until the fall to get the go-ahead from regulators.

Some experts, though, think it might be worth getting a second booster now if you face a high risk of Covid-19 exposure or if your previous dose was ages ago. The rise of BA.5 has spooked many of them, despite evidence the virus causes less severe disease now than at any other point during the pandemic. And despite the surge in cases, death trends have hardly moved, indicating that the previous crop of vaccines is still doing its main job of preventing severe illness for most people.

Adding to the confusion is that public health measures like face mask mandates and social distancing requirements are disappearing, increasing the chances of exposure. So managing the risks and response to Covid-19 is almost entirely up to you, the individual, and that can be tricky when there are so many moving parts.

To add a little clarity, here are answers to some key questions about Covid-19 vaccine boosters.

Who needs to get boosted and when? Should I get the original now or wait for the remix?

The current Centers for Disease Control and Prevention guidelines recommend a first booster shot for everyone 5 years old and up to be administered at least five months out from the initial doses of mRNA Covid-19 vaccines — the vaccines made by Pfizer/BioNTech and Moderna. People who received the one-dose Johnson & Johnson vaccine should get an mRNA booster at least two months out from the initial dose.

As for second boosters, if you’re over 50 or immunocompromised and the timing from your first doses works out, you should get the shot right away, says Andrew Pekosz, a professor of microbiology and immunology at Johns Hopkins University. “A booster now is going to help you avoid the hospital, and it’s something you need to do,” he explained.

If you’re not in a high-risk group — under 50 and pretty healthy — there’s no need to rush, according to Pekosz. Severe disease rates in people without other preexisting health conditions are extremely low. “I don’t think, right now, there’s a good reason to have relatively healthy individuals get a booster,” said Pekosz.

US health officials were concerned that if someone in this lower-risk category gets boosted now, they may have to wait longer to get a newer vaccine, since the minimum interval between boosters is several months. Getting booster shots too close together may not lead to an effective immune response and could also raise the risk of rare complications like myocarditis.

Because they’re expecting a larger spike in cases later this year, health officials want to allocate more resources to a fall vaccination campaign rather than trying to get younger people boosted now.

However, other researchers said that depending on an individual’s risk and exposure to Covid-19, it might make sense to get topped up right away. “I think there should be flexibility and permissiveness,” Anthony Fauci, chief medical adviser to the president, told the New York Times.

One factor is that the revamped vaccines offer better protection against the newer variants than the original formulations (more on that below), but the improvement may not be worth waiting for.

“To people asking, ‘Should I take the fourth dose now or wait for the new one,’ it’s not so much better that I would wait, because we’re in the middle of a wave. You should take what you can get now,” said Tania Watts, a professor of immunology at the University of Toronto. But while the bivalent vaccine isn’t perfect, it offers enough advantages to make it a preferred choice when it does become available. “I’ll probably take the bivalent vaccine when it’s available, because even if it’s incremental, it’s what we have,” she said.

What makes the booster shots different? How effective are they?

The reformulated booster doses of the mRNA vaccines from Pfizer and Moderna that the government is preparing to distribute this fall are “bivalent.” That means they contain the tools to target the original version of SARS-CoV-2 and its omicron variant.

Rather than delivering a whole inert virus or a fragment of it as conventional vaccines do, mRNA vaccines give human cells the genetic instructions for making pieces of the virus. In the case of the Covid-19 vaccines, they serve as an assembly manual for the spike protein of the virus. The bivalent vaccines contain mRNA instructions for making the spike protein of the original version of SARS-CoV-2 and the spike protein common to the BA.4 and BA.5 subvariants.

After you get a vaccine, your immune system revs up and starts making antibodies, which are proteins that bind to the virus and can stop it from causing an infection. If you have high levels of antibodies that can neutralize a virus, this usually means you’re well protected against infection. Antibody production, however, tapers off over time, so a vaccinated individual may be vulnerable to an infection after a few months. A booster shot ramps antibody production back up.

But antibodies attach best to very particular sites on the virus. If those sites mutate, as they have with the recent SARS-CoV-2 variants, antibodies become less effective at blocking infection. The bivalent vaccines restore some of this protection.

In clinical trials, the bivalent vaccines from Moderna and Pfizer/BioNTech did increase the level of neutralizing antibodies to omicron subvariants by less than two-fold compared to the original versions of their boosters. But the first round of booster shots raised antibody levels 25-fold or more, a result that’s led some researchers to say the bivalent shots aren’t a big enough improvement over the existing formula. That’s part of why there is some debate over getting boosters now to protect against the rising BA.5 wave versus waiting for a more targeted shot later this year. (Researchers have also noted that the results arose from trials of several hundred individuals, whereas the initial vaccines were tested in tens of thousands of people.)

One issue with deploying bivalent Covid-19 vaccines in the fall is that by the time they’re widely available, another variant or subvariant will likely be in circulation. That could erode their advantage over the original shots.

Another is that antibodies are not the whole story. They do decline and can leave an opening for infection, but other parts of the immune system can readily switch back on and stop an infection from causing too much damage. So far, researchers have found that the immune system’s memory cells — B cells and T cells — are still holding strong against the new variants in most people, even though they were trained with an earlier version of the virus.

And from a public health standpoint, the biggest concern isn’t preventing infection but preventing severe disease, where the virus causes enough damage to send people to the hospital or kill them. The initial Covid-19 vaccines still do the job of preventing severe disease well. A second round of boosters could blunt another surge of infections, but it’s not clear if that alone would be worth the money and effort, especially when tactics like face masks and social distancing also prevent infection. The risks from disease are also declining. There are now multiple effective treatments for Covid-19, too, so…