Some pending issues on the Oxford and AstraZeneca anti-Covid vaccine

For the moment it is not clear why a reduced dose of vaccine should be more effective: statistical "error" or "strange" immune responses?

(photo: Getty Images) A ​​70% efficacy, from 62 % of full dose at 90% of administration ½ + 1. Preliminary estimates of the efficacy of the Oxford-AstraZeneca anti-Covid vaccine, just released in a press release, are a headache. As with Pfizer-Biontech and Moderna vaccines, in fact, there are still no scientific publications available and more than one expert has expressed doubts at the announcement. Here's what's odd.

What does average efficacy mean?

The first thing that catches your eye is that the AstraZeneca release talks about an average efficacy of its vaccine against coronavirus by about 70% - a figure that arises by taking into consideration the total number of volunteers who have contracted Covid-19 (131) involved in the various trials. Yes, because the trial was not homogeneous: not all volunteers were treated equally.

A branch of the study instead of using a full dose of vaccine on the first administration gave half of it to its 2,741 participants . A mistake - defined Mene Pangalos, executive vice president of research and development of biopharmaceuticals at AstraZeneca, at the Guardian - to whose recognition, however, the researchers decided not to interrupt the trial, to proceed with a full dose booster four weeks later , and to note the effects of the different dosage. A lucky mistake, we could say in hindsight: at these doses the effectiveness of the vaccine seems in fact to reach 90%, against the uninspiring 62% of the whole dosage (a percentage which is in line with the estimated efficacy of vaccines against annual flu).

Do these data make sense? And if so, how are they explained?

Statistical doubts

Given that the data are not yet available and that it has not been said how the 131 cases of Covid-19 diagnosed were distributed among the different branches of the trial, there is who argue that the reason why a lower dose is more effective than the full dose depends on the disproportion between the two populations: the most effective arm involved 2,741 volunteers, while the less effective one 8,895. By expanding the studies, the discrepancy could vanish and the efficacy could equalize on a value close to 66%, speculates the epidemiologist of the London School of Hygiene and Tropical Medicine Stephen Evans in Nature.

Hypothesis in comparison

If the differences were confirmed, the question would be quite intriguing, at least from a scientific point of view. Although Oxford researchers admit in some interviews that they are still unable to explain why the initial half dose appears to provide better protection against coronavirus, the hypotheses on the plate are different.

According to immunologist Katie Ewer , who is working on the vaccine, for example, it is possible that a lower starting dose is more effective in stimulating a subset of immune cells (the T cells) that support the production of antibodies.

Another explanation Possible lies in the immune response to the viral vector used in the Oxford-AstraZeneca vaccine: some components of the modified chimpanzee adenovirus, used to induce immune cells to arm themselves against the coronavirus spike protein, could in turn induce a collateral immune reaction. A lower initial dose of the vaccine may have blunted this effect resulting in better protection from the coronavirus two weeks after the full-dose booster. This hypothesis, among other things, would also be supported by some tests on mice, which would also indicate a faster creation of memory immune cells.

We need more data

In short, the conclusion is that beyond the announcements it is not really known what the efficacy of the Oxford-AstraZeneca vaccine is nor the protection it could confer in the long term or on the younger and older sections of the population - data that is also lacking for the rest vaccine candidates who have completed phase 3 of testing.

For the scientific community to express itself, data is needed, and many more than those obtained so far. These will come in time.

Meanwhile, AstraZeneca will ask the relevant authorities to modify ongoing studies to include the dosing regimen that appears most effective. After all - the company says - it would be madness to use more vaccine than necessary, and moreover, to obtain a lower efficacy.