The Centers for Disease Control and Prevention (CDC) recently endorsed COVID-19 booster shots for adults age 65 and older, those ages 50 to 64 with underlying medical conditions, and people age 18 and older who live in long-term care settings, at least six months after receiving their second dose of the Pfizer-BioNTech vaccine. Two other groups that may also receive the booster according to the CDC are those ages 18 to 49 with underlying medical conditions and those 18 to 64 who are at increased risk due to their occupation. Currently, only people who are fully vaccinated with the Pfizer-BioNTech vaccine are eligible for the Pfizer booster shot.

According to NBC News, that leaves millions of people who received either the Moderna or the Johnson & Johnson vaccines without access to a booster. The Food and Drug Administration (FDA) said that mixing and matching vaccines could not be approved because of inadequate data on the efficacy and safety of such a move.

Dr. Dorian Fink, of the FDA’s Division of Vaccines said, “Consequently, the Pfizer-BioNTech vaccine is authorized for use as a booster dose among certain individuals who completed a primary series of the Pfizer-BioNTech vaccine.”

Surgeon General Vivek Murthy added that the FDA is working closely with Moderna and Johnson & Johnson to gather their data as quickly as possible so that the agency can formulate recommendations for COVID-19 booster shots from these pharmaceutical companies. Moderna asked for emergency use application for its booster earlier this month.

Experts predict that since both the Pfizer-BioNTech and Moderna vaccines use similar mRNA technology, approval should not be far behind for Moderna. Johnson & Johnson provided data from a recent Phase 3 clinical trial that showed positive results for its booster shot, says NBC, but has not yet applied for emergency use authorization.

Dr. Christina Rostad, a pediatric infectious disease expert at Emory University School of Medicine, said the reason the FDA nixed mixing and matching vaccines, is that there is very little scientific evidence of the efficacy of this procedure and “no evidence on mixing and matching delayed booster vaccines.”

The National Institutes of Health is currently conducting a clinical trial to see how people respond to boosters from different manufacturers, but is only in the first of two phases, according to NBC. Experts predict that people who receive a booster from a sister mRNA vaccine will be fine.

“What I think is a more interesting combination is the Johnson & Johnson vaccine followed by an mRNA booster,” said Dr. William Moss, a professor of epidemiology and an executive director of the International Vaccine Access Center at the Johns Hopkins Bloomberg School of Public Health.

The Johnson & Johnson COVID-19 vaccine uses an adenovirus to teach the immune system to protect itself.  Experts note that the mix-and-match approach is not new. The procedure is called heterologous prime-boost vaccination and the goal is to see if the combo increases immune response to the virus. According to The Wall Street Journal, mixing and matching vaccine doses isn’t a novel strategy. Heterologous prime-boost vaccination has been successful against other infectious diseases such as malaria, Ebola, and tuberculosis.

According to MIT Technology Review, studies have shown that mixing some vaccines did improve immune response. Top vaccine researcher Dr. Shan Lu, at the University of Massachusetts Medical School, who was one of the pioneers of the vaccine mixing strategy, says researchers do not fully understand how this mechanism works, but adds that the strategy might also make immunity last longer.

However, until the FDA sees scientific data on the safety and efficacy of getting a different COVID-19 booster shot, it is unlikely that the agency will give its blessings to the practice.

“This is how science should work,” said Dr. Steven Carsons, director of the Vaccine Center at NYU Langone Hospital in Long Island. “If the panel making these recommendations don’t feel the data is robust enough to make a firm recommendation, then they will modify the recommendation. This ensures that the benefit outweighs the risks.”