Outlook poses tough questions for next steps on COVID-19 vaccines

Vaccine modeling may not anticipate variants

Rochelle Walensky, director of the Centers for Disease Control and Prevention, has urged those with high-risk medical conditions and seniors over 65 to get a second booster. (Tom Williams/CQ Roll Call file photo)
Rochelle Walensky, director of the Centers for Disease Control and Prevention, has urged those with high-risk medical conditions and seniors over 65 to get a second booster. (Tom Williams/CQ Roll Call file photo)
Posted April 13, 2022 at 7:00am

Preparations for another potential round of COVID-19 vaccines are prompting more questions than answers as federal health officials contend with the threat of future variants amid waning public interest in additional shots.

The Food and Drug Administration and the Centers for Disease Control and Prevention last month OK'd a second round of boosters for anyone over 50 and certain people with compromised immune systems. CDC Director Rochelle Walensky has urged those with high-risk medical conditions and seniors over 65 to roll up their sleeves.

But the FDA's vaccine advisory committee last week debated whether more boosters for the broader public should be modeled off the original virus, or if scientists should create a unique vaccine series modeled off a newer variant. A similar CDC advisory committee will meet April 20 to continue the booster discussion, although the agenda has not been published.

The preparations will have potentially profound implications. Modeling vaccines on past variants may make them ineffective against a new variant. Complex recommendations on who should receive more shots may confuse the public message and add to booster fatigue. And officials must eventually decide what level of infection society can live with without continued boosting.

Vaccine effectiveness against omicron infection starts waning after roughly five months, and around half of people who previously had COVID-19 have been reinfected with omicron. The numbers have health officials pleading with the public to get a booster after their primary series, but so far only around half of eligible people have opted into the extra dose. 

“Everybody should go home and tell everybody you know, if you have not gotten the third shot, get it,” FDA Commissioner Robert Califf said at the AcademyHealth Datapalooza conference last week. “The next wave that comes through is going to pick off the people that haven’t gotten the third shot. The data is very clear.”

But a second booster for the broader public is posing more complicated questions. Health experts are grappling with the continued focus on antibody levels, rather than long-term memory B-cells and T-cells, which are harder to measure.

“We’re at risk of doubling down on a failed strategy,” Ofer Levy, director of the precision vaccines program at Boston Children’s Hospital, said at the FDA advisory committee meeting. “We’ve got to get into the immunology. Yes, there’s great labs out there doing amazing work, but where is the federal effort to coordinate all of that?”

Some experts question boosting with vaccines modeled on the original virus as new variants sweep the globe. The immune system responds most quickly to variants it has already encountered, and evidence has shown that people infected with a significantly different variant of a virus can potentially suffer worse reactions when a new wave hits. 

But it’s not yet clear if this is the case with COVID-19, or whether the current vaccines have broad enough protection to neutralize this phenomenon, known as “original antigenic sin.” 

“Theoretically, repeated exposure to an older variant formula may drive our immune system to concentrate too much on old features and not on new features,” Katelyn Jetelina, an assistant professor at University of Texas Health Science Center, wrote in her Substack newsletter. “But despite some truly surprising evolutionary leaps of the virus (like Omicron) we have not seen any convincing evidence of OAS among humans, which is great news.”

There's also disagreement in the medical community about whether more COVID-19 shots of any kind are necessary for the broader public beyond the elderly and high-risk. The debate has muddled the message on already confusing booster recommendations.

"The FDA and CDC have kind of come out with, like, a lukewarm, 'Yeah, you can do this,' as opposed to, 'Run and do it now.’ And you know, that's going to leave most people confused," said Jen Kates, Kaiser Family Foundation director of global health and HIV policy. 

Waning public interest

Health officials are also wrestling with what levels of infection and severe disease should be considered acceptable as the pandemic continues. Booster rates are trailing initial vaccination rates, and public interest in getting more shots will likely continue to decline. 

"What really keeps me up at night, it's the knowledge that we can't keep boosting, and we're going to have vaccine exhaustion," Peter Marks, director of the FDA Center for Biologics Evaluation and Research, said at last week's advisory meeting. "I'm not talking about immune exhaustion, I'm talking about physical exhaustion of people going to get boosted."

That dynamic is playing out in nursing homes and senior living centers around the country, where some of the nation’s most vulnerable individuals are cared for by some of the most vaccine-hesitant. 

John Knox Village, a retirement community in Pompano Beach, Fla., that includes nursing home facilities, has a 100 percent vaccination rate among its staff and 95 percent among its residents, according to Chief Operating Officer Bill Pickhardt. He said lower rates displayed by a federal regulatory site include short-term patients and inaccuracies.

But those numbers diverge when it comes to boosters. Among nursing home residents, 99 percent have been boosted compared to only 4 percent of the staff, according to federal data.

One reason is state law. Florida Gov. Ron DeSantis, a Republican who made a public appearance when John Knox Village received the state’s first vaccines in December 2020, signed a law last November barring Florida employers from imposing vaccine mandates. 

The state law is a roadblock for booster mandates at nursing homes like John Knox Village. An existing federal vaccine mandate for health care workers does not extend to boosters.

Pickhardt also attributed the vaccination gap among staff to skepticism in countries where many workers hail from, like Jamaica, Haiti and South Africa.

“There's just pushback because, culturally speaking, a lot of them come from countries where vaccines are frowned upon,” he said.

Roughly one-third of the community’s residents, meanwhile, are already registered to receive a second booster.

Better messaging

Marcus Plescia, chief medical officer at the Association of State and Territorial Health Officials, said states aren't running aggressive ad campaigns to encourage second boosters like they did for previous vaccinations.

Kates suggested the FDA and CDC should be more transparent about their methods and reasoning, beyond their appearances on the Sunday morning shows. As the country looks to additional boosters, much will depend on future variants and whether the U.S. stays in a COVID-19 lull or sees other variant spikes, she said. 

"What's difficult is, we are operating in a very strange world where this virus continues to change. We have to make the best decisions we can with limited data," she said, adding that "for the next stage of this, public meetings and deliberations are going to be essential."

The poor communication and slow uptake in the initial stages of the second booster rollout don’t necessarily bode poorly for future rounds of shots, Plescia said.

"I think there will be more uptake for a reformulated vaccine. Just anecdotally, what I hear from people is, 'Why do I have to get this again?’” he said. “With a reformulated vaccine, there's a clear answer. It's worth getting it again because it's different.”

That message will also run up against the same anti-vaccine forces that have plagued the federal vaccination campaign since its inception under former President Donald Trump. It’s a problem Califf acknowledged as one of the administration’s and the medical industry’s greatest challenges.

“We have to do something about misinformation, and hand in glove with that, improve our education about science at a very basic level,” Califf said. “It doesn’t help to have an understanding of data to action, if the facts don’t matter anymore.”