What’s the Right Dose for COVID Boosters?

The Biden administration says booster shots are coming, but the FDA hasn’t decided on the dose. Moderna wants a half-shot booster. Pfizer a full shot. But could the best dose for Americans and for the world be even less?

COVID-19 vaccines are the first successful use of mRNA vaccine technology, so a lot remains unknown. But identifying the smallest dose needed to provide effective boosting is critical to protect Americans from adverse effects, increase confidence in vaccines, and mitigate global vaccine inequity.

We’ve known since earlier this year that a half-dose of the Moderna vaccine produces antibody levels similar to the standard-dose and newer information suggests that even a quarter-dose vaccine may do the same. If a half or quarter dose is nearly as effective as a standard dose for first and second shots then a full dose booster may well be an overdose. The essential task of a booster is to “jog” the immune system’s memory of what it’s supposed to fight. Data from the world of hepatitis B suggest that the “reminder” need not be as intense as the initial “lesson.” And in the cases of tuberculosis, meningitis, and yellow fever vaccines, lower doses have been as good or better than the originals.

Lower doses could also reduce risks of adverse effects. Concerns about vaccine-associated inflammation of heart muscle, called myocarditis, in adolescents and young adults were validated in a large observational study out of Israel. Compared to lower doses of vaccine, boosting with the full dose may increase the risk of myocarditis. Presumably, this is why the FDA mandated Pfizer to study lower vaccine doses as a condition of granting full approval to the two-shot series.

The FDA demanding a similarly thorough process from boosters may bring added benefits. The majority of unvaccinated people cite side effects and safety concerns as major reasons for remaining unprotected. Reducing the booster dose to the smallest amount needed to generate an immune response might even help restore confidence in the regulatory process among the mildly skeptical unvaccinated.

The chosen booster dose also has profound implications for global vaccine equity. Producing boosters for developed countries will reduce the supply of first and second doses available to countries where most people haven’t received a first dose. A slower vaccine rollout in the developing world isn’t just unfair — it increases the death toll and likely facilitates the emergence of more variants. After all, it was from unvaccinated populations beyond America’s shores that the Delta variant first emerged.

The Biden administration says it wants 100 million boosters in 2021 alone. If we can boost 100 million Americans with the equivalent of only 25 million “full doses,” then the remaining 75 million doses that were budgeted for can be donated abroad to low-income countries who need the protection of first and second shots, potentially saving tens of thousands of lives while simultaneously enhancing our own safety. Vaccinating the world ought to remain a top priority both scientifically and diplomatically.

Both Moderna and Pfizer/BioNTech have ongoing trials with low-dose boosters using antibodies as their key endpoint. Consistent with the backbone the FDA has thus far shown in the booster debate, the agency should demand this data before approving a booster shot, or at the very least make full approval conditional upon its emergence. Preventing booster “over-dosing” is a straightforward but critical step to ensure that Americans are protected from adverse effects and also that the precious global vaccine supply is used optimally.

There is still time to avoid conspicuous vaccine consumption and reduce potential risks of rare adverse side effects by demanding that lower dose boosters be appropriately vetted and considered. Many lives and America’s global image depend on it.

The views expressed in this op-ed do not represent the views of the U.S. federal government or the authors’ employers.

Garth W. Strohbehn, MD, MPhil, is an assistant professor of medicine at the University of Michigan and a member of the Veterans Affairs Center for Clinical Management and Research, based in Ann Arbor, Michigan. William F. Parker, MD, PhD, is an assistant professor of pulmonary and critical care medicine at the University of Chicago and assistant director of the MacLean Center for Clinical Medical Ethics, based in Chicago, Illinois. Alex Tabarrok, PhD, is the Bartley J. Madden chair in economics at the Mercatus Center and a professor of economics at George Mason University, based in Arlington, Virginia.