Fractional dosing of COVID-19 vaccines can provide durable, long-lasting immunity comparable to full-dose boosters, according to a multi-year international study led by the Murdoch Children’s Research Institute (MCRI). Findings published across Nature Communications, Frontiers in Immunology, and the Journal of Infection suggest that reducing vaccine volume could lower costs and expand access to immunization in resource-constrained regions.

Evidence for Fractional Dosing Efficiency

Research involving over 2,000 participants across Australia, Indonesia, and Mongolia indicates that half-dose boosters maintain strong immune responses over a two-year period. While initial antibody levels following a fractional dose may be slightly lower than those from a full dose, the gap narrows significantly over time. Data from the Indonesian trial, which followed 1,200 adults, confirmed that immune protection remained comparable between the two dosing strategies at the 24-month mark.

In Mongolia, a companion study of 601 adults found that a fractional Pfizer booster provided antibody responses similar to a full dose for two years. Researchers also observed that cellular immune responses—vital for preventing severe illness—remained robust in the fractional-dose cohort. According to MCRI’s Dr. Nadia Mazarakis, these results offer a practical path for countries to extend limited vaccine supplies while maintaining high standards of public health protection.

Optimizing Booster Strategies for Future Pandemics

The implications of this research extend beyond COVID-19. CEPI Clinical Development Science Lead Amol Chaudari noted that these findings provide public health officials with a way to maximize vaccine utility during supply shortages. By utilizing fractional doses, health systems can protect more people quickly without compromising the efficacy of the immune response.

This approach is particularly relevant for low-income nations where healthcare spending as a percentage of GDP is significantly lower than in countries like Australia. The ability to stretch inventory could facilitate more equitable distribution of vaccines for future coronaviruses or other emerging pathogens like mpox, Ebola, or hantavirus, according to Associate Professor Paul Licciardi of MCRI.

Timing and Vaccine Selection

Beyond dosage, the research team identified other variables that influence immune performance. A study published in the journal Vaccine revealed that administering mRNA vaccines in the morning, rather than the afternoon, yielded improved immune responses. This effect was not observed with protein-based vaccines, suggesting that simple scheduling adjustments could enhance the effectiveness of specific booster programs.

In Australia, researchers compared mRNA and protein-based vaccines as a fourth dose. Both platforms successfully reduced infections and maintained comparable immunity over 12 months, though mRNA vaccines generated higher antibody levels. The study has secured an additional $2 million in funding from the National Health and Medical Research Council (NHMRC) to track these participants for 30 months to observe the impacts of repeated vaccination.

Frequently Asked Questions

Can a half-dose of a vaccine really protect against COVID-19?

Yes. According to MCRI-led trials, fractional (half) doses produce immune responses that remain comparable to full-dose boosters over two years, providing long-lasting protection.

Does the time of day affect vaccine efficacy?

Research published in Vaccine suggests that receiving an mRNA booster in the morning can improve immune response compared to afternoon administration, though this does not apply to protein-based vaccines.

Why is this research important for low-income countries?

Fractional dosing allows health authorities to “stretch” existing vaccine supplies. This reduces costs and increases the number of people who can be vaccinated, which is critical for countries with limited healthcare budgets.

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