COVID-19 | Halving the first dose of AstraZeneca improves its potency, study finds

A dosing error made during a vaccine trial against the COVID-19 of AstraZeneca and the University of Oxford (United Kingdom) has led to a new finding of the dosage in mice, according to a new study from Northwestern Medicine (United States).

During the AstraZeneca / Oxford trial, some human participants mistakenly received half a dose of their first injection, followed by Paradoxically, the trial showed that volunteers who received a lower dose of the first injection were better protected against COVID-19 than those who received two full doses.

However, it was not clear whether the improvement from the low-dose vaccine was due to the dose itself or the fact that people who received the lower dose as well and the second injection, which is known as an interval of expanded reinforcement.

Now these scientists have tested the effect of an initial dose of SARS-CoV-2 vaccine in mice and have found that a lower first dose, followed by a full booster dose,

The study, published in the journal Science Immunology, concluded that the booster injection produced more antibodies and T cells in the mice, allowing them to develop against SARS-CoV-2.

Vaccine clinical trials use a method known as dose escalation, in which a person receives a lower dose and is boosted with that same lower dose; a second person receives a higher dose and is reinforced with that same higher dose, and so on.

The idea is to make sure the vaccine is safe, so scientists use dose escalation to determine the minimum dose of vaccine that can be given to someone without

The Northwestern study did not use the AstraZeneca / Oxford vaccine, but a similar one: an adenovirus serotype 5 vaccine that is similar to the CanSino vaccines, developed in China, and Sputnik V, developed in Russia. Now new studies from this research group are looking at this dosing regimen in mRNA vaccines.

Why did the lower dose work better?

In the trial, participants who received the first full dose received a booster around three to four weeks after the first injection, while those who received the lower dose had a much longer booster interval. The Northwestern study reproduced this extended boost interval in mice, and also reported that the

“An extended interval between prime and boost allows the immune system to rest and mature so that the immune response can expand more robustly after the booster vaccination. The longer you wait before boosting, the better that secondary immune response will be ”, explains one of those responsible for the study, Pablo Penaloza-MacMaster.

However, this can be a tricky game, because waiting longer to boost the vaccine could “In the event of a pandemic, it is an ethical challenge to extend the booster interval because people need to be fully protected as soon as possible. But this approach may have its advantages in terms of improving the durability and magnitude of long-term immune responses, which can be useful not only for SARS-CoV-2 vaccines, but also for other vaccines. ” , the scientist points out.

The team also observed similar positive effects when reducing vaccine doses with an experimental adenovirus vector-based HIV vaccine, suggesting that these findings may be generalizable to other vaccines.

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