The Current COVID-19 Booster-Shot Strategy is Not Sustainable, Says FDA's Expert Panel
While the currently available COVID-19 vaccines remain effective in protecting people from serious disease, public health experts still face a handful of important questions about the shots and their ability to continue to protect against the virus in coming years. Will a new version of the vaccine be more effective? How long does protection last? Are boosters the only way to extend that protection? Is there a better, more coordinated way to give vaccines and boosters to maximize immunity in the face of an ever-changing virus?Those were the discussion topics that the U.S. Food and Drug Administration’s addressed in a day-long virtual meeting on April 6. The 28-member committee of independent experts reviewed the available data on vaccine effectiveness and tried to lay the foundation for maximizing the effect of vaccines in curbing COVID-19.
Because public health experts at the Centers for Disease Control and Prevention (CDC) and regulators at the FDA are still learning about how the virus works, and what type of immunity is needed to control it, the U.S.’s vaccination strategy has relied on a game of catch-up: chasing after waves of infections first with the primary vaccinations and then with booster doses to keep those waves from cresting and overwhelming the health care system with sick patients.
For now, the vaccination schedule is a complicated algorithm depending on which vaccine people get, as well as their age and health status.
The Pfizer-BioNTech mRNA vaccine, for example, is , meaning two doses, for adults 16 and over, and allowed under emergency use authorization for children five years to 15 years old. An dose is recommended for anyone over age 12, but for children 5 to 11, the booster is only advised for those with weakened immune systems. The Moderna mRNA vaccine is a, and for a third, booster dose for this age groups as well. The Johnson&Johnson-Janssen vaccine is with a second booster dose for adults 18 and older.
The FDA also a second booster dose (fourth shot) of both Pfizer-BioNTech’s and Moderna’s vaccines for people over age 50 and those with compromised immune systems.
The complex guidelines in part led the FDA to call its committee together in order to come up with a more systematic and effective vaccination strategy moving forward. Currently, 70% of the U.S. population that is eligible to get vaccinated has received their primary immunization—two doses of mRNA vaccines from Pfizer-BioNTech or Moderna, or one dose from Johson&Johnson-Janssen. Only about 50% of this group has received a booster dose.
In addition to the confusing recommendations, studies show that the immunity provided by the vaccines, including the boosters, wanes. The panel heard from CDC scientists, who reported that in studies in which blood serum from people who are fully vaccinated with their primary doses was mixed with the Omicron variant, there was a 25-fold drop in antibodies that could neutralize that variant; among those who were boosted, there was still a 6-fold drop in that neutralization activity.
That means the current booster strategy isn’t sustainable, so the committee discussed ways to establish a more structured plan for studying vaccine effectiveness and making decisions about whether, and when to change the shots or boosters.
One strategy they discussed was the influenza model: With the annual flu shot, an expert panel of scientists invited by the World Health Organization analyze data on the genetics of circulating influenza viruses as well as how much disease they cause. They then recommend which strains of influenza should be included in the annual shot, and health departments in various countries generally follow this advice when making their annual flu vaccines.
That model isn’t entirely applicable to SARS-CoV-2, since researchers don’t fully understand its genetic changes and what they might mean for causing human disease. The variants that have morphed from the original virus so far, including Alpha, Beta, Delta and Omicron, do not represent any pattern or predictable progression from one set of mutations to the next. That’s very different from the influenza virus, which generally does change in broadly predictable ways.
In addition, while most flu vaccines are built the same way, by growing the desired influenza strains in chicken eggs and then generating specific flu proteins to include in the shots, there’s a range of approaches used in COVID-19 vaccines, with some relying on mRNA, some on recombinant viral proteins, and still others on viral vectors to deliver viral messages to the immune system.
Further, with COVID-19, it isn’t clear that an annual vaccine like the influenza approach would make sense, But what would drive that change isn’t entirely obvious either. “The issue of how we decide when the vaccine needs to be modified, and what is going to be the threshold where we say so much escape from vaccine immunity requires a change—that’s such a difficult question to answer,” said Dr. Cody Meissner, director of pediatric infectious disease at Tufts Medical Center, and one of the FDA committee members.
Such decisions would have to be made using data that may not be the gold standard that the committee members would ideally like to see, for practical reasons. If new versions of the vaccines are needed that target different variants, those vaccines would still need to go through safety and clinical testing. Ideally, that would come from months-long studies of people who have been vaccinated and then exposed to the virus, to see if they get infected, and if they do, how sick they get.
But, for example, to have enough new shots ready for a wave of cases in the fall, they would have to be tested and manufactured by May or June. So the committee members discussed the possibility of using the sort of lab-based studies that have driven the authorizations and approvals to date, in which scientists test blood from people vaccinated and measure how well the antibodies the shots produced can neutralize the virus.
