Why Covid-19 vaccine boosters may be more important than ever

Less than half of eligible Americans — only about a third of the total US population — have gotten a first booster dose, according to the US Centers for Disease Control and Prevention. Only about 10 million people have received a second booster, which is authorized for people 50 and older, along with those who are 12 and older who are moderately to severely immunocompromised.

Getting more Americans boosted against Covid-19 could make a big difference as far as case numbers go, according to Dr. Peter Marks, director of the Center for Biologics Evaluation and Research at the US Food and Drug Administration. He told the American Medical Association on Monday that he is “a little concerned” about where the Covid-19 pandemic is heading.

“It’s really important that we try to get the half — or a little bit more than a half — of Americans who have only received two doses to get that third dose,” Marks said. “That may make a difference moving forward here, and it may particularly make a difference now that we’re coming into yet another wave of Covid-19.”

Case rates are currently highest in the Northeast region of the US, where booster uptake is best. Nearly half of Vermont’s population is fully vaccinated and boosted, along with more than 40% of the population in Maine, Rhode Island, Connecticut and Massachusetts, according to CDC data.

But cases are also starting to tick up in the South, where less than a quarter of the population is fully vaccinated and boosted. In North Carolina, Alabama and Mississippi, less than 1 in 5 people have received their booster shot.

Who’s getting — and not getting — boosters

Adults who were initially vaccinated with the mRNA vaccine are eligible for a booster dose five months after the initial series. Those vaccinated with Johnson & Johnson are eligible for a booster dose two months after their first shot.

CDC data shows that booster uptake is higher in older age groups in the US, consistent with broader vaccination trends. But nearly 2 out of 5 seniors age 65 and older — and more than 3 out of 5 adults overall — do not have either of their booster shots.

Scientists are still trying to determine whether younger age groups would benefit from an additional vaccine dose. Pfizer and BioNTech have requested emergency use authorization for the 5-to-11 age range.

“That will hopefully be acted on in the not-too-distant future,” Marks said.

New research on fourth doses

The researchers gave study participants whose median age was 70.1 years a half dose of the Moderna vaccine or a full dose of the Pfizer vaccine in a random selection in January, about seven months after they received their first booster. The second booster didn’t seem to have any major side effects. The biggest complaints were arm pain and fatigue.

The booster also generated an immune response at day 14 that was higher than that at day 28 after the third dose of the Pfizer or Moderna Covid-19 vaccine.

When the researchers compared the mRNA vaccines, Moderna’s fourth dose seemed to do slightly better than Pfizer’s, but it’s unclear why. Both generated what scientists considered a “significant fold change” in protective antibodies. T-cell responses were also boosted after the fourth dose.

Antibodies are a first line of immune protection that can stop a virus from infecting cells. T-cells come in later and destroy infected cells. T-cells can’t protect against mild infections, but they can keep infections from progressing to severe disease.

“Fourth-dose Covid-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity,” the study says. “Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose.”

The study also showed that some people who had higher levels of antibodies before the fourth dose of the Covid-19 vaccine had only “limited” boosting. Those with a history of Covid-19 infection had a similar limited response. The authors say this suggests that there may be a ceiling or maximum response that can come with a fourth vaccine dose.

The study didn’t look specifically at neutralization of the Omicron variant.

New generation of vaccines and boosters

Marks hopes that the next generation of Covid-19 vaccines — which he predicts will come in the next year or two — will be even better at protecting people against the “whole variety” of Covid variants and provide a more robust immune response.

The FDA’s vaccine advisory committee will meet in late June to review the data on vaccines, including monovalent (which would target a single variant) and bivalent vaccines (which could target the original strain of the virus plus another).

“It’s a little bit of a challenge here because we don’t know how much further the virus will evolve over the next few months,” Marks said. “But we have no choice, because if we want to produce the hundreds of millions of doses that need to be available for a booster campaign, we have to start in the early July timeframe or even sooner to get those kinds of numbers.”

The FDA committee may also discuss whether an additional booster should be recommended in the fall for the general population or for target groups, Marks said.

Some doctors have said they’ve heard from patients who want to wait to get a booster to get better coverage for winter. Marks said that waiting to get a booster is a bad idea, especially if those people haven’t had Covid-19 recently.

“Why? Because it’s going to be four or five, six months before we get to when you get your next booster,” he said. “You’re talking about having several months there at risk.”

Even with a fall and winter surge predicted, cases are on the increase now, and those who have had only two mRNA shots are vulnerable.

“Rather than just being casual about it,” Marks said. “I would urge them to try to get that third dose to ramp up the immunity just because we do have plenty of circulating Covid-19.”