When Dr. Nadia Mazarakis and her team started comparing half-dose COVID-19 boosters to full doses, they expected to find some trade-offs. Instead, they discovered something remarkable: the smaller shots worked just as well for up to two years.
The finding comes from a major research program led by the Murdoch Children's Research Institute in Melbourne, Australia. More than 2,000 people across three countries—Australia, Indonesia, and Mongolia—took part in clinical trials that tracked how their bodies responded to different vaccine doses over time.
"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," Dr. Mazarakis said.
The implications are significant. Half-dose boosters, sometimes called fractional dosing, could help stretched healthcare systems get more shots from the same amount of vaccine. That means lower costs, wider coverage, and better access for communities that have historically struggled to get vaccines.
In Indonesia, researchers followed more than 1,200 adults for two years after they received either half or full doses of Pfizer, AstraZeneca, or CoronaVac vaccines. The results, published in the journal Nature Communications, showed that while fractional doses produced slightly lower immune responses right after vaccination, those differences disappeared over time. By 24 months, both doses were providing comparable protection.
A companion study in Mongolia followed 601 adults who received a fractional Pfizer booster. That research, published in Frontiers in Immunology, found the half-dose produced long-lasting antibody responses similar to a full dose for the full two years. The same group also showed strong cellular immune responses—these are the cells that help protect against serious infections.
Meanwhile, an Australian study of 496 healthy adults compared mRNA vaccines (like Pfizer and Moderna) to protein-based boosters. Published in the Journal of Infection, it found mRNA vaccines generated higher antibody responses, though both vaccine types reduced infections and produced comparable protection over 12 months. The promising results recently earned the research team an additional $2 million in funding from Australia's National Health and Medical Research Council to continue following participants for 30 months.
Amol Chaudari, who leads clinical development science at CEPI (a global coalition working on pandemic vaccines), called the findings a way to get "more bang for your buck" with COVID boosters. If cases were to surge again and vaccine supplies tightened, these strategies could help countries expand coverage quickly and prevent future infections and deaths.
Perhaps surprisingly, the research also found that when you get vaccinated matters. A separate analysis published in the journal Vaccine showed that morning vaccinations produced better mRNA immune responses than afternoon shots—though the timing didn't affect protein-based vaccines. It suggests a simple scheduling change could offer meaningful benefits.
Dr. Mazarakis emphasized that while the acute phase of the pandemic has passed, COVID-19 still poses risks, and these findings will help public health officials around the world plan smarter, more equitable vaccination programs for years to come.