ACIP Champions ‘Mix and Match’ Booster Strategy

The CDC’s Advisory Committee on Immunization Practices (ACIP) came out strongly in favor of heterologous, or “mix and match,” boosters in two unanimous votes on Thursday.

ACIP voted 15-0 that certain populations authorized to receive a booster dose of COVID-19 vaccine who received a Pfizer or Moderna primary series receive a booster at least 6 months later, including adults ages 65 and up, adults ages 18-64 with high-risk medical conditions, and adults ages 18-64 at high occupational or institutional risk for COVID exposure. They also voted 15-0 that adults who received a Johnson & Johnson single-dose primary regimen receive a booster dose of COVID-19 vaccine at least 2 months later.

This was a switch from the CDC staff’s initial presentation to ACIP this afternoon, which proposed recommending that individuals try to receive a homologous booster. In a media briefing last night, FDA officials said they had no preferential recommendation for heterologous or homologous boosters.

Amanda Cohn, MD, of the CDC, clarified that a preferential recommendation for heterologous boosters was “outside the intent of the FDA” emergency use authorization (EUA), “but allowing for it is acceptable,” she added.

Indeed, the committee appeared to heed the charge of CDC Director Rochelle Walensky, MD, who spoke at the beginning of the meeting. After thanking ACIP members for their time and dedication, she urged them to “never lose sight of our collective goals to protect as many people as possible from COVID.”

Following a presentation from CDC staff with language that favored homologous boosters, committee members spoke up about the need for the option for heterologous use.

In addition to emphasizing the “good data” that heterologous boosting appears to boost immune response, Helen Keipp Talbot, MD, of Vanderbilt University in Nashville, spoke about practical considerations, such as using up an available vial of mRNA vaccine rather than having to open a second vial and “throwing the rest away.”

Camille Kotton, MD, of Massachusetts General Hospital in Boston, noted that this mix-and-match approach would help with equity.

“We are seeing people who are quite savvy … and they seem to be advocating for some of the more robust approaches to booster vaccines,” she said, adding that heterologous boosters would “allow better flexibility so clinicians in the field can more easily adapt.”

Some on the committee feared that the broad swath of individuals covered by the “high risk of occupational or institutional exposure” would lead the “worried well” to get unnecessary boosters. Sarah Long, MD, of Drexel University in Philadelphia, characterized the lax definition of this group as “smoke and mirrors and underhanded and winks and nods,” saying it separated people into “haves and have nots.” She argued there was no evidence that any healthy person under age 50 needed a booster.

However, the majority of the committee felt that guidance about populations who may be at increased risk of rare adverse events, such as vaccine-associated myocarditis, thrombosis and thrombocytopenia syndrome (TTS), and Guillain-Barré, could be covered in the clinical considerations document from the CDC.

Matthew Daley, MD, of Kaiser Permanente Colorado in Aurora, suggested that the clinical considerations document might be a “reasonable risk mitigation strategy,” even though “the vote language is front-page news and the clinical considerations don’t receive much attention.”

And Beth Bell, MD, of the University of Washington in Seattle, emphasized the need for clear and simple language in the ACIP’s recommendations.

“An important aspect of all this is being clear and not dancing on the head of a pin so that we don’t confuse the American people,” she said. “We risk sacrificing what’s best overall for the purposes of purity.”

All recommendations from the ACIP are not considered final until they are published in the Morbidity and Mortality Weekly Report.