In an abrupt change of course, President Joe Biden’s health advisers announced Wednesday that all Americans should expect to receive booster shots eight months after their last shot beginning in the fall.

The White House’s top health experts — including chief medical adviser Anthony Fauci, Centers for Disease Control and Prevention Director Rochelle Walensky and Food and Drug Administration Acting Administrator Janet Woodcock — said that they have seen the ability of the vaccines to protect people from getting sick diminish, and worry that could be an early warning sign that protection against hospitalization and death will wane over time.

They emphasized protection against severe disease and mortality from COVID-19 is still robust at the moment. Nearly all the cases of severe disease, hospitalization, and death are in unvaccinated people.

Booster shots for all Americans would begin the week of Sept. 20, with those vaccinated earliest in the vaccination rollout, including health care providers, nursing home residents, and other seniors first in line.

“Based on our latest assessment, the current protection against severe disease, hospitalization, and death could diminish in the months ahead, especially among those who are at higher risk or were vaccinated during the earlier phases of the vaccination rollout,” reads a statement by Biden’s top health experts. “For that reason, we conclude that a booster shot will be needed to maximize vaccine-induced protection and prolong its durability.”

Or, as Biden said in an address later Wednesday, “It will make you safer and for longer.”

The booster plan is still subject to an independent FDA evaluation and recommendation by the CDC’s vaccine advisers. Biden plans to speak about the plan later on Wednesday.

Third doses are likely to offer an added layer of protection to people vulnerable to a breakthrough infection from the highly infectious and more deadly delta variant, and could help communities cope with surging cases without pricey lockdowns.

But the move could have devastating consequences for global supply, consuming hundreds of millions of vaccines while 99 percent of people in low income nations have not gotten their first shot.

Biden dismissed the concerns of the World Health Organization that dealmaking between drugmakers and the U.S. for booster shots has deprived such nations of those first doses.

“I know there are world leaders who say Americans shouldn’t get a third shot until other countries got their first shot. I disagree,” he said, citing a pledge to donate 500 million vaccine doses to other nations by mid-2022.

While the Biden administration predicts the extra dose will better protect against severe disease and death in the months ahead, so far those benefits are hypothetical.

“In the first six months where we saw high rates of vaccination in high income places and nearly nothing in low income places, that is the unfortunate global health paradigm,” said Aaron Richterman, a global health expert and an infectious disease fellow at the Hospital of the University of Pennsylvania. “This is something even slightly different than that, where we’re getting additional vaccinations based on very little evidence when we know these are life saving interventions in low income settings. … It may be a new low bar.”

The administration’s move also comes ahead of the FDA analyzing the pharmaceutical companies’ clinical trial data on third doses and the CDC analyzing its own real-world studies. Many experts called the announcement premature.

“It may be the right decision — let’s see the data — but if it were the Trump administration getting this far out ahead of FDA and CDC on something this significant, there’d be outrage. And appropriately so,” said Jason Schwartz, a Yale public health professor, in a tweet Tuesday.

Pfizer submitted phase 1 data on a third booster shot earlier this week.

Walensky previously said studies of cohorts of health care workers and other essential workers tested weekly would serve as an early alarm bell if immunity was shown to wane. Those studies are not expected to produce results until the fall, according to CDC presentation slides released last week.

The CDC’s independent advisers on vaccines, the Advisory Committee on Immunization Practices, will meet on Aug. 24 to discuss next steps on booster shots.

Justification studies

In a press briefing Wednesday, Fauci and Walensky outlined the observational and lab studies underpinning the decision to recommend boosters for all.

In a CDC study published Wednesday, vaccine effectiveness in more than 14,000 nursing homes declined on average from 75 percent to 53 percent through Aug. 1. However, the study authors stated that the findings are “not generalizable” outside of nursing homes.

Meanwhile, researchers in New York found vaccines remained about 92 to 95 percent effective at preventing hospitalizations among the vaccinated from May to late July, but found effectiveness at preventing symptomatic disease fell from 92 percent to 80 percent as delta spread.

A third study showed that vaccine effectiveness against hospitalization remained strong for at least six months, but Walensky cautioned few of the cases sequenced were of the delta variant. “Taken together, these data confirm that while protection against infection may decrease over time, protection against severe disease and hospitalization is currently holding up pretty well,” Walensky said. “As we make decisions about boosters though, we also have to look at vaccine effectiveness in the specific context of the delta variant.”

Walensky went on to cite preliminary data from one of the agency’s cohort studies that showed vaccine effectiveness against infection declining from 92 percent to 64 percent. The report is not published yet.

David Holtgrave, a coauthor of the New York study and dean of the University at Albany School of Public Health, has criticized the CDC for not collecting and publishing more surveillance data on breakthrough cases to inform decisions on boosters. CDC stopped tracking mild and moderate breakthrough cases in May.

Holtgrave said the recommendation around boosters, in addition to ramped up masking and social distancing, is consistent with the results of his study. “I was pleased that federal officials were looking at data for today but also thinking through where the pandemic might be in the weeks ahead, and trying to come up with strategies to stave off even worse trends,” he said in an email.

But there are drawbacks to changing policy before a more robust clinical trial, and relying too much on observational studies like the ones CDC cited or the lab studies Fauci cited.

Part of the challenge is that the drugmakers have yet to land on a reliable “correlate of protection” — a biological signal that someone is protected from infection or not — so policymakers and clinicians are making their best guesses as to whether someone is protected based on limited data.

Neutralizing antibodies are the easiest to measure in a lab, and Pfizer and Moderna executives have cited these lab studies in order to stress the urgency of booster doses. But waning antibodies is natural, experts say, while other immune cells that rev up when an infection occurs are likely to last for years.

“Neutralizing antibodies are a good correlate of protection but they are not the only one,” said Christian Bréchot, president of the Global Virus Network.

“Our memory B cells are primed to produce antibodies adapted or evolved towards the variants if they encounter a variant. The complexity and in-breadth response of antibodies generated by our memory B cells will cover future variants,” said Monica Gandhi, a professor of medicine at the University of California, San Francisco, in an email.

Concerns about variables

Some have raised concerns about “confounding variables” — biases controlled for in the sort of clinical trial that FDA would analyze, but which could bias observational studies like those the CDC cited.

For example, older adults vaccinated early on may see declining immunity not because eight months have passed, but because immune systems become more vulnerable with age. They also wonder whether a third dose of a vaccine trained to home in on the original virus will be highly effective against delta.

“Those antibodies will cover the ancestral strain because that is what the mRNA in the vaccines code for,” said Gandhi. “The majority of the symptomatic breakthroughs among the vaccinated are mild, which can be prevented by fit and filtered masks.”

As a result, some critics remained unmoved by the new CDC data.

“There is nothing here to directly support use of boosters generally,” Richterman said. “A small drop in protection against largely mild disease with delta does not justify this, because it’s not at all clear that using a booster of the same vaccine, which is similarly off-target from delta, will be beneficial.”

Fauci acknowledged that they were moving ahead of the data, but cautioned against risking lives by moving too slowly. “If you wait for something bad to happen before you respond to it, you find yourself considerably behind your real full capability to respond,” he said.