• The FDA and CDC OKed a second booster shot for people age 50 and older last week.
• The decision was based on data from Israel, which rolled out fourth doses months ago.
• Dr. Peter Marks, who heads the FDA office responsible for vaccine safety and efficacy, said shortly after the decision that another round of boosters will likely be needed in the fall.

Leading U.S. scientists and physicians worry that the FDA and CDC are moving too fast in approving a fourth round of Covid shots, with little public debate that gives the vaccine makers too big a role in setting the pace with which the doses are distributed across the nation.

The top U.S. public health agencies last week endorsed a fourth Covid shot for older adults without holding public meetings, drawing criticism from leading vaccine experts who believe federal health officials haven't provided enough transparency about the reasons for the decision.

The authorization of a fourth dose for adults age 50 and older comes as the scientific community is divided over whether the data is sufficient to support another round of boosters, and whether authorizing additional shots is a sustainable public health policy, especially since protection against infection simply wears off over time. There is a debate over whether the goal of the vaccines is to prevent severe illness, which they've largely achieved, or infection as well — a more challenging proposition.

The Food and Drug Administration authorized a second booster shot for people age 50 and older last week, and the Centers for Disease Control and Prevention quickly backed their distribution hours later based on data from Israel, which rolled out fourth doses months ago. Dr. Peter Marks, who heads the FDA office responsible for vaccine safety and efficacy, said shortly after the decision that another round of boosters will likely be needed in the fall.

Rapid approval

The rapid regulatory clearance of fourth shots for older adults came just weeks after Pfizer and Moderna asked the FDA to permit them. Several FDA and CDC committee members as well as other leading experts said Pfizer and Moderna are playing too large a role in setting the agenda around U.S. vaccine policy by announcing the need for fourth doses and possibly a variant-specific vaccine before the public health agencies have made any recommendations.

Moderna CEO Stephane Bancel said during a January interview with Goldman Sachs that fourth doses would be needed in the fall as the protective antibodies from the shots wane over time. Pfizer CEO Albert Bourla told CNBC in early March, before the company filed its request with the FDA, that there's a need for a fourth dose though he said the regulators would ultimately come to their own conclusion.

"I just think it's sort of booster mania. I think the companies are frankly acting like public health agencies," said Dr. Paul Offit, a member of the FDA committee and one of the nation's top vaccine experts. Offit said the CDC, which has the final say on vaccine recommendations, needs to develop a clear national strategy to reduce public confusion about what it means to be fully vaccinated at this stage in the pandemic.

Michael Osterholm, a leading epidemiologist, said repeated boosting is not a sustainable public health strategy due to the challenge posed by waning immunity against infection. "We're not gonna be able to boost our way out of this," said Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Call for more transparency

The FDA and CDC vaccine advisory panels weigh safety and efficacy data before making recommendations to top federal health officials on the best path forward. Though the recommendations are nonbinding, the meetings provide an open forum where the public can listen to the nation's top health experts debate the pros and cons of vaccine policy and often even participate by phoning in to voice their views.

The FDA's Vaccines and Related Biological Products Advisory Committee is meeting Wednesday to debate the future of boosters. However, they will not vote on any specific recommendations, according to the FDA. The CDC's Advisory Committee on Immunization Practices also did not meet before CDC Director Dr. Rochelle Walensky signed off on the fourth shots for older adults last week.

"It's just sort of fait accompli," Offit said. "I feel that we're in a time, this sort of Covid exceptionalism, where we don't do things the way we normally do it, which is that the science precedes the recommendation. Here, it's the other way around," Offit said.

Offit said that the FDA is effectively asking the public to believe that the data supports a fourth dose by providing sufficient protection against serious illness. He said the American public benefits from hearing an open discussion about vaccine decisions, particularly at a time when many people are not taking advantage of the third dose. Offit is an infectious disease expert at Children's Hospital Philadelphia and a co-inventor of a rotavirus vaccine.

Marks, during a call with reporters last week, said the FDA did not call a committee meeting because the decision was "relatively straightforward." He said data from Israel suggested a fourth dose can reduce the risk of hospitalization and death in older adults. The CDC, in a statement to CNBC, said the fourth dose was an incremental change that did not need to go before its committee.

Dr. William Schaffner, a non-voting member of ACIP, disagreed that the CDC recommendation was an incremental change. Schaffner said clearing fourth doses for older adults is a big decision that would have benefited from a meeting of outside advisors to provide the public with transparency.

"I think to have this decision made in house behind closed doors without having the transparency of a full debate that a regularly called ACIP meeting would have provided –I think that's unfortunate," said Schaffner, an infectious disease expert at Vanderbilt University Medical Center.

Dr. James Hildreth, who is attending the FDA committee's Wednesday meeting as a temporary member, noted that the drug regulator wasn't required to call a public meeting before authorizing the shots, and the agency has seasoned experts who can determine if there is evidence to support a new authorization. However, Hildreth said moving forward with out a recommendation from outside experts creates bad optics.

"When the FDA makes a decision like that without calling together an outside group of experts, it just adds to the optics of the pharmaceutical companies having an impact on decisions that are being made," said Hildreth, president of Meharry Medical College in Nashville, Tennessee. Meharry is a clinical trial site for Novavax's vaccine as well as Moderna's shots for younger children.

'Diminishing returns'

While some health experts believe the central purposes of the vaccines is to prevent severe illness, others think it is important to also stop infections from the virus. The protection provided by the Pfizer and Moderna vaccines against infection has declined substantially over time, particularly in the context of omicron, which has numerous mutations that give it an enhanced capability to cause breakthrough infections and mild illness. However, the vaccines are still providing substantial protection against severe illness.

"If you've gotten a mild illness after you've been vaccinated, you've won — that's it. You've been prevented from having serious illness, which is the stated goal of this vaccine," said Offit, who believes three doses were necessary for the elderly and four for the people with weak immune systems, but is skeptical of the need for additional shots right now.

But if the goal is also to prevent infection, that means, at least for now, booster shots are the only available tool to increase antibodies until a longer lasting vaccine is available. The problem is that the vaccines eventually run into diminishing returns, according John Moore,  a professor of microbiology and immunology at Weill Cornell Medical College. Moore said a three-dose regimen is fairly standard with vaccines to help boost the immune system to its peak response. The fourth shot, however, begins to hit a ceiling — at least in terms of protecting younger people against infection.

The Israeli Health Ministry and scientists at Sheba Medical Center found that a fourth dose does restores antibodies that waned off after a third dose among health-care workers ages 18 and older, but it provided little protection against infection. Pfizer cited that study, which has not undergone peer review, among others in its statement on the FDA authorization, focusing on the increased antibodies without highlighting the issues with breakthrough infections.

Different age, different needs

Dr. Peter Hotez, a vaccine expert at the Baylor College of Medicine in Houston, strongly supports a fourth dose for older adults, pointing to a CDC study from February that found the third shot's effectiveness against hospitalization dropped from 91% to 78% after four months.

Pfizer, in its public statements on the fourth dose, cited a separate Israeli study that found a fourth dose reduced mortality by 78% in people ages 60 and over. The study from Ben Gurion University and Clalit Health Services, which has not undergone peer review, analyzed the medical records of more than 500,000 people.

'We continue to collect and assess all available data and remain in open dialogue with regulators and health authorities to help inform a Covid-19 vaccine strategy as the virus evolves," Pfizer said in a statement to CNBC.

While the Ben Gurion study may point in the direction of benefit for older adults at the moment, the evidence for boosting younger adults again is scant as the U.S. considers lowering the eligibility for fourth doses sometime later in the year.

Dr. Gili Regev-Yochay and her team of scientists at Sheba said a fourth dose "may only have marginal benefits" for younger people, according to a letter published in the New England Journal of Medicine. While Pfizer originally filed for adults age 65 and older, Moderna asked the FDA authorize a fourth dose for ages 18 and older. Moore called Moderna's filing "aggressive," arguing that it didn't distinguish between the needs of the elderly, who may benefit from an additional dose, compared with younger adults where the data is less convincing.

Moderna CEO Stephane Bancel told CNBC last month that the company wanted to give the FDA flexibility to decide which age group would benefit most from a fourth shot right now. Moderna, in its public statements on its application for a fourth dose, pointed to data from Israel but didn't cite specific studies.

Though Hotez supports a fourth dose for older adults, he said the FDA and the CDC have not done an effective job at communicating whether the goal of the vaccines is to prevent severe illness, infection or both, and the vaccines makers have filled that void with statements on data from their clinical trials and lab studies. Hotez and a team of scientists in Texas developed a Covid vaccine, Corbevax, based on traditional protein-based technology that has received authorization in India.

Hotez also expressed frustration that the U.S. relies heavily on data from abroad, particularly Israel and the U.K. Offit also questioned why the U.S. is relying on data from countries that are smaller than the U.S. and have different demographic backgrounds.

Long-term strategy needed

Hildreth said the U.S. should put off additional booster doses as long as the public health situation allows so the nation can more clearly define how it measures protection against the virus and develop a long-term strategy to achieve that end. He said if the public is asked to get boosted every several months, many people will simply stop listening.

"We don't know a specific measure we can do to say whether or not a person is truly protected, and whether or that's the same with everybody," said Hildreth. For example, there's no clear measure of whether a certain level of antibodies is sufficient to protect people, Hildreth said.

Beyond vaccination with the current vaccines, Pfizer and Moderna are developing shots that target omicron as well as other variants. Dr. Arnold Monto, who is chairing the FDA's committee meeting on booster strategy Wednesday, said public health authorities need to develop a consensus about what goes into the vaccines moving forward. Monto said collaboration between the vaccine makers and the government is crucial, but industry has started playing larger public role in decisions about about what kind of vaccines should be developed to target specific Covid variants.

"Industry has a double-headed goal. They are trying to do public good like we all are. They also have stockholders, and we need to be sure that the public health good is kept mind," Monto said.