Fractional COVID booster doses provide strong long-lasting immunity

Smaller doses of COVID-19 booster vaccines can provide long-lasting immunity, helping to reduce costs and improve access to vaccination, according to new research. And the findings could also inform vaccine dosing and options during future pandemics.

An international research program led by Murdoch Children's Research Institute (MCRI) and involving more than 2,000 participants across Australia, Indonesia and Mongolia has provided new evidence that will help shape future COVID-19 booster strategies. 

The $17.6 million program, funded by the Coalition for Epidemic Preparedness Innovations (CEPI), evaluated different COVID-19 booster approaches through three randomized clinical trials, tracking participants for up to two years. 

The trials found fractional doses, where people receive half the standard vaccine amount given as boosters, produced strong immune responses that remained comparable to full-dose boosters.

MCRI Dr Nadia Mazarakis said fractional dosing could help extend vaccine supplies, widen coverage and improve equity in future vaccination programs, particularly in low-income countries. 

This research provides valuable evidence showing that smaller vaccine doses can still provide strong, long-lasting immunity, which is encouraging for countries looking for practical and affordable ways to deliver booster programs.

Fractional dosing attracted global interest during the COVID-19 pandemic when vaccine supplies were limited. While circumstances have changed, the findings remain relevant because they show there may be opportunities to use vaccines more efficiently without compromising immune responses.

Importantly, these vaccine strategies will reduce costs, extend supplies and support broader and more equitable access to booster programs, especially in resource constrained countries across Southeast Asia and Africa." 

Dr. Nadia Mazarakis, MCRI

CEPI Clinical Development Science Lead Amol Chaudari said, "These pivotal insights - produced across different countries, with different vaccines and people who had received different first COVID vaccine doses - essentially show that public health officials can get 'more bang for their buck' with COVID vaccine boosters. If COVID cases were to ramp up again and there be strain on the vaccine supply, these findings could be key to expanding vaccination coverage quickly and preventing future infections and deaths. The findings could also prove helpful for future vaccines against other coronaviruses manufactured using similar technologies."

Results from the Indonesian study, published in Nature Communications, followed more than 1,200 adults for up to two years after receiving either fractional or standard doses of Pfizer or AstraZeneca vaccines, or a standard CoronaVac vaccine.

The researchers found that while fractional doses produced slightly lower immune responses shortly after vaccination, those differences narrowed over time and remained comparable to full doses at 24 months. 

A companion study of 601 Mongolian adults, published in Frontiers in Immunology, discovered a fractional Pfizer booster produced long-lasting antibody responses similar to a full dose for two years. A further analysis of the same cohort reported that key cellular immune responses, which help protect against serious infections, also remained strong.

In Australia, researchers compared mRNA and protein-based booster vaccines as a fourth full dose. Published in the Journal of Infection, the study involving 496 healthy adults found mRNA vaccines generated higher antibody responses. Both vaccine types reduced infections and produced comparable immune responses over 12 months. The study recently received a further $2 million from the National Health and Medical Research Council (NHMRC) to follow the cohort for 30 months to examine the effects of repeated mRNA COVID-19 vaccination.

Additional research from the team published in Vaccine, found vaccination in the morning, rather than afternoon, improved responses to the mRNA vaccine, but not the protein-based vaccine. The findings suggest simple changes to vaccination timing may offer meaningful benefits.

MCRI Associate Professor Paul Licciardi said while the acute phase of the pandemic had passed, COVID-19 remained a significant cause of respiratory illness and death globally. 

"Understanding how long vaccine-induced immunity lasts remains important for future vaccination planning," he said. "As countries move towards long-term management of COVID-19, we need evidence about which booster strategies provide durable immunity while making the best use of healthcare resources.

"This knowledge can also help future public health strategies to combat emerging pathogens like hantavirus, Ebola and mpox."

Australia spends about 10 per cent of its gross domestic product (GDP) on healthcare, compared with 4.4 per cent in Mongolia and 2.7 per cent in Indonesia, highlighting the importance of identifying vaccination strategies that maximize the impact of available resources. 

MCRI Associate Professor Claire von Mollendorf said, "These trial results demonstrate that shaping effective public health policy requires monitoring long-term immune responses across diverse settings with variable infection rates and different primary vaccine schedules."