More From Less: Optimizing Vaccine Doses

During COVID, I argued strongly that we should cut the Moderna dose in order to expand supply. In a paper co-authored with Witold Więcek, Michael Kremer and others, we showed that a half dose of Moderna was more effective than a full dose of AstraZenecs and that doubling the effective Moderna supply could have saved many lives.

It’s not just about COVID. My co-author on the COVID paper, Witold Więcek, has found other examples where a failure to run dose optimization trials cost lives:

Take the human papillomavirus (HPV) vaccine. For years after its introduction, countries administered it as a three-dose series. Then additional evidence emerged; eventually, a single dose proved to be non-inferior. This policy shift, driven by updated World Health Organization (WHO) guidance, has been a game-changer—massively reducing delivery costs while expanding coverage in low- and middle-income countries (LMICs). But it took 16 years from regulatory approval to WHO recommendation. Had this change been implemented just five years earlier, the paper estimates that 150,000 lives could have been saved.

Knowing the potential for dose optimization should encourage us to take a closer look at what we can do now. Więcek points to two high-opportunity projects:

• The pneumococcal conjugate vaccine (PCV) is already Gavi’s top cost driver, consuming $1 billion of its 2026–2030 budget. But new WHO SAGE guidance, from March 2025, suggests that in countries with consistently high coverage (≥80–90 percent over five years), either one of three shots could be dropped, or each of the three doses can be lowered to 40 percent of the standard dose. While implementation requires sufficient epidemiological surveillance, its cost would be offset by significant savings in vaccine costs: a retrospective analysis suggests that for the 2020–25 period this approach could have led to as much as $250 million in savings.
• New tuberculosis vaccines, currently in phase 2–3 trials, are another high-impact example. Given initial promising results, a future vaccine could prove highly effective, but may also become a significant cost driver for countries and/or Gavi—and optimization may prove highly beneficial both in terms of health and economic value.

Witold’s new paper is here and here is excellent summary blog post from which I have drawn.

Addendum: See also my paper on Bayesian Dose Optimization Trials and from Mike Doherty Particles that enhance mRNA delivery could reduce vaccine dosage and costs.