Smaller COVID-19 vaccine booster doses match full-dose protection for up to two years

Reducing the size of COVID-19 vaccine boosters doses still produces strong immune responses that remain over time, a new multi-year research project run across several countries has found.

CEPI-funded clinical trials involving over 2000 people in Australia, Indonesia and Mongolia who received fraction of a standard sized shot of a licensed COVID-19 vaccine, like those produced by Pfizer-BioNTech and AstraZeneca, showed long-lasting antibody and cellular immune responses comparable to full-dose boosters for up to two years.

Findings from the research programme, led by Australia’s Murdoch Children’s Research Institute, could play help vaccine doses reach more people, while also potentially reducing the costs of running future COVID-19 vaccination programmes. 

“While COVID infections have significantly reduced over the past few years, these dose-sparing insights could be majorly beneficial in guiding national health policies around booster shots” explains Dr Amol Chaudhari, Clinical Development Science Lead at CEPI.

Should COVID-19 cases spike again in the future, this evidence could also inform future dosing strategies – showing that we can extend the vaccine supply and protect more people from the vaccine resources available.

“The findings remain relevant because they show there may be opportunities to use vaccines more efficiently without compromising immune responses” said MCRI’s Dr Nadia Mazarakis.

“Essentially it shows 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”, added Chaudhari.

Administering reduced vaccine shots - also known as fractionation - has previously been used to maximise global vaccine supply during outbreaks of Yellow fever and Polio. 

Recognising the unexplored potential of fractional dose strategies specifically for COVID-19 vaccines, CEPI announced funding to support MCRI’s research as part of efforts to increase access to shots worldwide in 2022 when there was restricted supply.

The investment supported three randomised controlled trials across diverse populations where there had been variable COVID-19 infection rates and people had received different authorised COVID-19 vaccines as their first and follow-up doses. 

The research in Indonesia, which recruited more than 1200 adults, found immune responses generated following receiving a fractional dose of a Pfizer of AstraZeneca vaccine was slightly lower to a full booster dose on initial vaccination but then produced comparable levels over time which remained in a subset of the participants for two years.

Another trial in Mongolia found a half-sized dose of the Pfizer booster produced long-lasting antibody responses similar to a full dose for two years. Equally, research in Australia showed comparable immune responses for standard-dose boosters for an mRNA and protein-based vaccines which remained over 12 months. Australia’s National Health and Medical Research Council has now provided further funding to the trial to follow the group of study volunteers for 30 months to look at the longer-terms effects of mRNA COVID-19 booster vaccination. 

“What’s remarkable is that similar findings in terms of the level of immune response from fractional dosing were consistently produced across different countries – including in middle-income nations - with different vaccines and in people who had received different first COVID vaccine doses” says Chaudhari. 

CEPI invested a total of USD 12.3 million in the research.