Lower doses of COVID-19 booster vaccines may provide longer-lasting immunity, reducing costs and improving access to vaccination, according to a new study. The findings could also inform vaccine doses and options during future pandemics.
An international research program led by the Murdoch Children’s Research Institute (MCRI) and involving more than 2,000 participants from Australia, Indonesia and Mongolia has provided new evidence to help shape future strategies to prevent the spread of COVID-19.
The $17.6 million program, funded by the Coalition for Epidemic Preparedness Innovations (CEPI), evaluated various COVID-19 booster approaches through three randomized clinical trials that followed participants for up to two years.
Trials found that split-dose booster doses of half the standard vaccine dose produced as strong an immune response as a full-dose booster.
MCRI’s Dr. Nadia Mazarakis said split doses could help expand vaccine supply, expand coverage and improve equity in future vaccination programs, especially in low-income countries.
This study provides valuable evidence that lower vaccine doses can provide strong, long-lasting immunity, which is reassuring for countries looking for practical and affordable ways to deliver booster immunization programs.
Split dosing gained global interest during the COVID-19 pandemic, when vaccine supplies were limited. Although the situation has changed, the results of this study remain important because they show that vaccines may be used more efficiently without compromising the immune response.
Importantly, these vaccine strategies will reduce costs, expand supply, and support broader and more equitable access to booster vaccination programs, particularly in resource-constrained countries in Southeast Asia and Africa. ”
Dr. Nadia Mazarakis, MCRI
Amol Chaudhary, CEPI Clinical Development Scientific Leader, said: “These vital insights were obtained in different countries, with different vaccines, and in people who received different initial COVID-19 vaccinations, essentially allowing public health officials to ‘get more benefit’ with COVID-19 vaccine boosters.” “If coronavirus cases rise again and vaccine supplies become strained, these findings could be key to rapidly expanding vaccination coverage and preventing future infections and deaths.” Coronaviruses manufactured using similar technology. ”
Research results in Indonesia have been announced. nature communicationsfollowed more than 1,200 adults for up to two years after receiving either the Pfizer or AstraZeneca vaccine, or a split-dose or standard dose of the standard CoronaVac vaccine.
The researchers found that while the split dose produced a slightly lower immune response immediately after vaccination, the difference narrowed over time and remained similar to the full dose at 24 months.
A joint study of 601 Mongolian adults revealed that Frontiers of immunologyfound that Pfizer’s fractional booster produced similar long-lasting antibody responses for two years as the full dose. Further analysis of the same cohort reported that the important cell-mediated immune response that helps protect against serious infections also remained strong.
In Australia, researchers compared mRNA and protein-based booster vaccines as a fourth full dose. Published in infection journala study of 496 healthy adults found that mRNA vaccines generated higher antibody responses. Both types of vaccines reduced infections and produced comparable immune responses over 12 months. The study, which recently received an additional $2 million in funding from the National Health and Medical Research Council (NHMRC), followed the cohort for 30 months and investigated the effects of repeated mRNA COVID-19 vaccinations.
Additional research by the team has been published. vaccinefound that vaccinating in the morning rather than in the afternoon improved responses to mRNA vaccines, but not protein-based vaccines. The findings suggest that simply changing the timing of vaccination may yield meaningful benefits.
MCRI Associate Professor Paul Ricciardi said that although the acute phase of the pandemic has passed, COVID-19 remains a significant cause of respiratory illness and death globally.
“Understanding how long vaccine-induced immunity lasts remains important for future vaccination plans,” he said. “As countries move towards long-term control of COVID-19, evidence is needed on booster strategies that provide sustained immunity while maximizing health care resources.
“This knowledge will also inform future public health strategies to combat emerging pathogens such as hantavirus, Ebola, and mpox.”
Australia spends approximately 10% of its gross domestic product (GDP) on health care, compared with 4.4% in Mongolia and 2.7% in Indonesia, highlighting the importance of identifying vaccination strategies that maximize the effectiveness of available resources.
MCRI Associate Professor Claire von Mollendorf said: “These trial results demonstrate that developing effective public health policies requires monitoring long-term immune responses in diverse settings with fluctuating infection rates and different primary vaccination schedules.”
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Murdoch Children’s Research Institute
References:
- Hart, J.D.; others. (2025) Immunogenicity of split-dose and standard-dose COVID-19 vaccine boosters in healthy Indonesian adults: 24-month follow-up from a randomized controlled trial; Nature Communications. DOI: 10.1038/s41467-025-63598-6. https://www.nature.com/articles/s41467-025-63598-6
- Tsetsegusaihan Batmunk, T. others. (2026) Fractional BNT162b2 booster after non-mRNA priming induces durable immune responses in Mongolia: a randomized controlled trial. Frontiers of immunology. DOI: 10.3389/fimmu.2026.1789248. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1789248/full
- Mazarakis, N. others. (2026) Immunogenicity and efficacy over 12 months after the fourth dose of bivalent mRNA- or protein-based COVID-19 vaccines: a randomized controlled trial in Australia. infection journal. DOI: 10.1016/j.jinf.2026.106727. https://www.journalofinfection.com/article/S0163-4453(26)00052-6/fulltext
