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The University of Oxford’s COVID-19 vaccine candidate, developed in partnership with the biotech AstraZeneca, is the third vaccine this week to publicize promising data from its clinical trials. And, in a surprising twist, it appears that a lower dose of the vaccine does a better job at protecting participants from COVID than a higher dose.
On Monday, Oxford announced that its adenovirus-based vaccine is on average 70% effective, according to preliminary phase III data, which might not seem that impressive at first glance. But a closer look reveals that this figure is actually an average of the vaccine’s performance in two arms of the of the study, which performed quite differently.
So what was the difference? Like the vaccines being developed by Pfizer and Moderna, the Oxford vaccine is administered in two doses given one month apart. Approximately one quarter of participants received a first dose that was only half of the regular dose, rather than two full doses. The group that received a reduced first dose were 90% less likely to contract COVID than the placebo group, while the two full dose regiment was only 62% effective. These numbers seem to run contrary to conventional wisdom about vaccine dosing.
It’s important to keep in mind that these results are drawn from preliminary data, and that this discrepancy could disappear when looking at larger groups of patients. But if the “half-dose, full-dose” approach is truly more effective, there are a couple of potential explanations. Researchers have suggested that it could be due to a lower first dose creating a better response among T cells, or more quickly establishing memory B cells. The later explanation is also consistent with adenovirus vaccine research done in mice.
If a lower first dose really is more effective, it might mean that the vaccine could be distributed more quicky to more patients within the same manufacturing confines. Even better, the Oxford vaccine is stable at refrigerator temperatures, meaning that it is be easier to transport and store than the Pfizer’s vaccine, which must be kept at -70 degrees Celsius. This could be especially important for smaller, rural hospitals with fewer resources.