Get your booster shots already

by Faye Flam

Fewer than half of eligible Americans have received a third COVID vaccine shot despite clear evidence of its benefit. That booster shot improves your odds of avoiding even mild omicron. So why haven’t more people gotten it?

One reason may be that we’re all over map in our risk of getting infected. That variability could be causing confusion over who should get how many booster shots and when. “I’m confused, and I’m on the FDA advisory committee,” said Paul Offit, director of the vaccine education center at the Children’s Hospital of Philadelphia, on a recent video conference.

Another part of the problem is the term booster, he said. It might be clearer to redefine full vaccination to encompass two, three or four shots depending on various individual risk factors. But figuring that out won’t be easy, since there are factors besides age and being immune-compromised that matter. Some people’s antibodies hold up better than others and work better fighting the current variants.

That’s why some people are getting COVID two or three times and others have never gotten it at all. About one in four Americans still haven’t been infected with COVID-19, according to some estimates — and as far as I know, I’m one of them, though it’s also possible I had an asymptomatic case. I’ll find out soon, since I just gave a blood sample for a study that can decipher this and a lot more from the mix of antibodies I carry.

Though a third shot is obviously not 100% effective — nothing in medicine is — it vastly improves your odds of avoiding omicron, which is the family of variants that have dominated since the end of last year, said Duane Wesemann, an immunologist who is heading the study. He told me that earlier studies from his lab and others show that the third mRNA shot gives most of us more than a temporary increase in antibodies. It also improves the quality of our antibodies. The way he explains it, antibody-making cells, called B-cells, can grow to different levels of maturity. The most mature B-cells carry different mutations that allow them to produce antibodies with more diversity, improving the odds that some will be good at attacking the new variants that keep evolving.

The first two shots (or one shot of the J&J vaccine) still protect most of us against severe disease because our bodies retain virus-fighting T-cells, which are a sort of backup line of defense. They won’t stop you from getting sick, but they will kick in to prevent the disease from becoming severe. But without any further shots, the circulating antibodies that had provided an earlier line of defense do almost nothing to stop an infection with omicron and its sub-variants BA.2 and BA.2.12.1.

The first two mRNA shots might have been too close together to allow these B-cells to mature, he said, and so the longer interval to the third shot might explain why those who received it make antibodies that neutralize omicron 20 to 30 times better than the initial shots.

The long-term goal of Wesemann’s new study, the one I enrolled in, is to find a pan-coronavirus vaccine — one that could protect people from COVID variants that have yet to evolve as well as any new coronaviruses we might encounter in the future. It’s being conducted through the Ragon Institute, a collaboration of Harvard, MIT and Massachusetts General Hospital.

So far they have more than 200 volunteers and they’re still accepting more. Lab tests that will be done on the samples can detect past infection in vaccinated people by looking for antibodies to a protein called nucleocapsid, which isn’t elicited by the vaccine but is part of the full virus. They can also look at how my vaccine-induced antibodies are holding up.

Unfortunately, unless you’re enrolled in a study like this one you probably don’t know how good your current protection is. Vaccine protection wanes over time but not in a predictable or uniform way. Wesemann said some people are “sustainers” — they clear the virus easily when infected and retain a strong set of immune cells and antibodies. Understanding how could help scientists design a better vaccine.

It could also help doctors give better advice about who needs a fourth shot. Right now, the benefits of a second booster are far less clear. Offit, who is on the FDA advisory committee, said during that video conference in mid-May that he’s had his third shot, but not the fourth. He’s waiting for more evidence of a benefit.

There’s no reason to wait on that third, shot, though. In fact, Wesemann said my booster, received way back in December, may have protected me against getting BA.2.12.1, an omicron variant now surging in the Northeastern US. It’s supposed to be the latest in an ever-escalating series, about 25% more transmissible than BA.2, which has been estimated to be 30% more transmissible than the initial omicron, itself a whopping 50% more transmissible than the already wildly contagious delta, which had a 50% advantage over the highly transmissible alpha.

Some experts qualify these numbers by saying the variants might not be that much more inherently transmissible but instead are progressively better at evading immunity from past variants and the vaccines. Genes, past coronavirus infections and many other factors might also influence who getting infected despite a booster.

The message that everyone’s going to get COVID might not be true, and the message that everyone is at risk undersells the value of that first booster. It’s an odds game, so why not stack them in your favor by getting that extra shot?

Faye Flam is a Bloomberg Opinion columnist covering science. She is host of the “Follow the Science” podcast.