Is a quarter-dose of Moderna vaccine enough?

According to a preprint study, two shots of the Moderna COVID-19 vaccine, each containing only one-quarter of the standard dose, generated neutralising antibodies and T cells comparable to natural infection. 

The results open the door to the possibility of administering fractional doses of the mRNA vaccine to accelerate the global immunisation effort.

In the original trial of the Moderna COVID-19 vaccine, participants were randomised into three groups. Each received either 25, 100 or 250 micrograms of the vaccine. This kind of study helps scientists determine the dose that triggers the best immune response with the lowest side effects.

The highest dose was too toxic. The lowest dose elicited the weakest immune response. The middle dose offered the best balance. The 100 microgram dose, which several countries ultimately approved for mass use, triggered strong immunity and had a good safety profile. 

In a later study, Moderna scientists found that two half-dose jabs elicited an immune response as good as the standard dose.

In this most recent study, scientists analysed blood from 35 participants of the original trial who had received two 25 microgram injections of vaccine 28 days apart.

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Read more: What’s in a COVID vaccine?

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Six months after the second dose, nearly all of them had developed neutralising antibodies – which block the virus from infecting cells – and T cells, which destroy infected cells stopping the infection. Levels of both antibodies and T cells were comparable to those found in people who have recovered from COVID-19.

Reducing the vaccine dose means that more doses could be administered from each vial. This could mitigate supply shortages and allow low-income countries to access more vaccine doses.

Clinical trials aiming to confirm the efficacy of reduced vaccine doses are ongoing. But some scientists think fractional doses should be used before these lengthy trials are completed.

In a commentary published in Nature Medicine, infectious disease experts from the University of Chicago and the University of Hong Kong support such an approach to cope with the global vaccine shortage.

“Shortages in the supply of vaccines have been a particular problem for low-income countries, which have collectively received only 0.2% of all vaccines delivered worldwide for approximately 10% of the world’s population. 

“Fractionation of vaccine doses is a potential solution to this global shortage of vaccines that has not been given sufficient attention and consideration,” they wrote.

A vaccine dose-reduction approach was successfully adopted in 2016 when limited supplies of a vaccine that took a minimum of 6 months to manufacture left millions of people in Africa and South America vulnerable to an epidemic of yellow fever.

Then, the World Health Organization’s Strategic Advisory Group of Experts on Immunization recommended dose fractionation down to one-fifth of the standard dose after reviewing the evidence on the immunogenicity and safety of the yellow fever vaccine.

It is a difficult conundrum, says Associate Professor Hassan Vally, an epidemiologist at La Trobe University. “It is a trade-off that depends on the context of each country, what variant is circulating and how good immunity is provided against the variant that is circulating.”

“In some situations, waiting a much longer time to develop immunity that is not very strong may not achieve much,” he says. “But there may be situations in which there is no prospect of getting enough vaccines that one might say something is better than nothing.”