Smaller “fractional” doses of COVID-19 booster vaccines may deliver long-lasting immunity while stretching limited supply—an approach that could lower costs and expand access during future waves, according to a new multinational study.
The research program, led by Murdoch Children’s Research Institute (MCRI) and supported by CEPI, enrolled more than 2,000 participants across Australia, Indonesia, and Mongolia. Participants were followed for up to two years, allowing investigators to track the durability of immune responses beyond the early post-vaccination window.
Across three randomized clinical trials, investigators compared fractional boosters—administering half the standard dose—with full-dose boosters. The key immunological measure was whether reduced dosing meaningfully weakened the quality or longevity of the response, rather than only how quickly antibodies rose after vaccination.
In Indonesia, a trial followed adults who received boosters based on either Pfizer or AstraZeneca schedules, including a comparator standard CoronaVac booster group. Fractional dosing produced somewhat lower immune responses soon after vaccination, but the gap narrowed over time and reached similar levels at 24 months.
A parallel study in Mongolia examined adults receiving fractional BNT162b2 boosters after non-mRNA priming. Researchers reported that antibody levels remained sustained for two years, and an additional analysis showed that cellular immunity—T cell responses associated with protection against severe disease—also persisted strongly.
The Australian work broadened the question of booster optimization by comparing a bivalent fourth dose using mRNA versus protein-based platforms. While mRNA boosters generated higher antibody responses, both vaccine types reduced infections and maintained broadly comparable immune profiles over a 12-month follow-up period.
Beyond booster dose itself, the team evaluated practical variables such as vaccination timing. Findings indicated that administering mRNA vaccine in the morning improved immunogenicity, while protein-based vaccines did not show the same time-of-day effect.
Together, these results suggest that future booster strategies could use dose-sparing regimens to improve “coverage per vial” without sacrificing immune durability—an especially relevant goal for resource-constrained settings.
Subject of Research: People
Article Title: Immunogenicity and efficacy over 12 months following a fourth dose of a bivalent mRNA or protein-based COVID-19 vaccine: A randomised controlled trial in Australia.
Web References: https://www.nature.com/articles/s41467-025-63598-6 ; https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1789248/full ; https://pubmed.ncbi.nlm.nih.gov/41833643/
References: 10.1038/s41467-025-63598-6; 10.3389/fimmu.2026.1789248; 10.1016/j.jinf.2026.106727; 10.3389/fimmu.2026.1779435
Keywords: COVID-19, fractional dosing, booster vaccines, immunogenicity, randomized controlled trial, mRNA vaccines, protein-based vaccines, antibody durability, cellular immunity
