How do boosters work and how can we celebrate Eid safely this year?
During an outbreak of Yellow Fever in Brazil in 2018, there was a global shortage of vaccines.
In the face of those limitations and the virus’s rapid spread, health officials in Brazil decided to administer fractional dosing. They gave people one-fifth of the normal dose.
More people got protection in less time and the outbreak was contained.
Fractional or lower dosing has been used around the world for years as a means to overcome vaccine shortages.
In 2016, it was used in Angola and the Democratic Republic of Congo during Yellow Fever outbreaks there. Now, evidence suggests that it could be done with some COVID-19 vaccines.
While 3.79 billion vaccine doses have been administered worldwide, 73.1 percent of the global population has yet to receive one, according to Our World in Data.
As many rich countries reopen after vaccinating most of their citizens, in lower-income countries only 1.1 percent of people have received at least one dose.
“A fractional dose is a better dose than no dose at all and it’s better than many vaccines currently in use,” said Alex Tabarrok, professor of economics at George Mason University.
‘Immunity lower but comparable’
In a new preprint study, scientists have looked at data from Moderna’s early trials.
During those stages, trial participants were given a variety of dose sizes.
In the end, it was the 100 microgram dose that was taken to phase three and beyond. But the data showed that seven months after receiving two quarter doses of 25 micrograms each, participants had a similar immune response to a full dose.
According to this and another study, the T-cells and neutralising antibodies in quarter and half doses were comparable to the full dose.
“The immunity is lower but comparable,” said Alex Sette, professor of immunology at La Jolla Institute for Immunology and co-author of the new study on quarter dosing of the Moderna vaccine.
“It may be just as effective as 100 [micrograms].” But he thinks that more studies need to be done.
‘Save a lot of lives’
As early as January 2021, Moncef Slaoui, head of the United States’ vaccine development programme, Operation Warp Speed, suggested lower dosing.
He said that a half dose of Moderna would have the same effect as a full dose. But many worried about the lack of data.
The concern is that with a lower dose there will be a lower overall efficacy.
But a small drop in a vaccine with 95 percent efficacy would still be considered a highly effective jab and would be a better option than many people have currently.
“Coming down from 95 to maybe eighty-something, that’s still going to most likely have a very high efficacy against severe disease, close to 100 percent. That can save an awful lot of lives given the limited supplies of vaccines,” said Ben Cowling, professor of infectious disease epidemiology at the University of Hong Kong.
Modelling in one study on lower dosing suggests that a 70 percent effective vaccine available now versus a 95 percent effective vaccine in two months, would reduce deaths by 20 to 37 percent. As variants emerge and almost three-quarters of the world remains unvaccinated, the race to vaccinate as many people as possible continues to be urgent.
“There’s no reason to think they initially settled on the right dose,” said Michael Kremer, an author of the modelling study and professor in economics and public policy at the University of Chicago. “I don’t even think we should presume that [lower dosing] is less efficacious.”
The study looked at lower dose data from several vaccines and suggests, though the data is still limited, that a half-dose of AstraZeneca could be more effective than a full dose.
Scientists have also found that lower doses reduce side effects, a major cause of vaccine hesitancy. In Brazil, some trial participants were accidentally given a half-dose of AstraZeneca. They reported fewer side effects and scientists found they had a good immune reaction.
The young, who have stronger immune systems and as a result tend to have stronger side effects, could benefit. Moderna is already considering half doses for children, and lower doses could play an important role in booster shots.
Rolling out lower dosing
The lower dosing trials have been small and more study needs to be done to definitively say how effective they will be.
There are some ongoing studies including one for Pfizer in Belgium. But some scientists say we do not need to wait to roll it out.
“The studies that have already been done are sufficient to seriously consider fractionation,” said Cowling.
Countries like the United Kingdom tried a ‘first-dose first’ rollout, in which the four-week window between doses was lengthened to eight-to-twelve weeks.
“They took an educated bet which over time has seemed to be the right one to have taken and other countries followed suit,” said Amrita Ahuja, co-author of the modelling study and director at the Douglas B. Marshall, Jr. Family Foundation.
The UK had about the same evidence for ‘first-dose first’ as there is now for lower dosing. She said a similar thing might occur instead of, or in parallel to, the time-consuming phase three trials for lower doses.
In developing the vaccines, a process that normally takes years was done in months.
“When you’re rushing, you’re looking for anything that works well,” said Kremer.
“Now it makes sense to go back and say, ‘Can we get something that’s effective with a lower dose?’ and thereby both reduce side-effects and be able to vaccinate many more people.”
It could be, he added, that once we go over the data, we would find that a half dose could have been considered a full dose all along.
“I think,” said Cowling, “we should probably be getting away from the idea of maximising the effectiveness in one person and get towards the idea of choosing the vaccine dosing so that we can save the most lives.”
If lower doses are used, the global vaccine supply increases. If the dose is effective in preventing death and severe disease, it would play a significant part in helping bring the pandemic to an end.