The Covid-19 vaccine battle: which is the most effective? How to measure it?

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Efficiency of 94.5%, 95% or 70% "on average" with a paradoxically better result with a lower dose: the race for the vaccine against Covid-19 is also a battle of numbers, as spectacular as it is difficult to interpret For the general public.

How do we measure effectiveness?

Among the volunteers in each trial, some receive the vaccine and others a placebo, to be able to compare. Volunteers lead normal lives during the trial. Over time, some will naturally catch Covid-19. If the vaccine is effective, the number of sick people will be less in the participants who have been vaccinated than in those who have received the placebo.

In theory, a vaccine is 100% effective if no patient identified in the trial belongs to the group of vaccinated volunteers. The results recently announced by several competing teams concern the last stage of their clinical trial, phase 3, for which tens of thousands of volunteers have been recruited.

These results were released as soon as a predefined number of Covid patients was reached among the volunteers: 95 for the American laboratory Moderna (November 16), 170 for the American-German alliance Pfizer / BioNTech (November 18) and 131 for the European project AstraZeneca / University of Oxford this Monday 23.

What results?

Pfizer / BioNTech is 95% effective: of its 170 patients, 8 came from the vaccinated group and 162 from the placebo group. The same or almost the same for Moderna, with 94.5% efficacy (5 patients in the vaccinated group, 90 in the placebo group). Pfizer measured the effectiveness of its vaccine one week after the second and last injection, and Moderna two weeks later.

For their part, AstraZeneca and the University of Oxford announced this Monday an average efficiency of 70%, calculated from the results of two different protocols. Efficacy is 90% for volunteers who first received a half dose and then a full dose a month later. It drops to 62% for another group, which was nevertheless vaccinated with two full doses one month apart. A paradox that is only apparent, according to specialists.

"We all hoped that two full doses would give the best response. But apparently a lower starting dose is better for priming the immune system to give a better response later," explained one of the researchers responsible for the project, Andrew Pollard, in Press conference. This could be because a lower starting dose "better mimics what happens during a real infection," according to colleague Sarah Gilbert.

Another hypothesis: it could also come from the technology used by this vaccine. AstraZeneca and the University of Oxford have in fact relied on the "viral vector" technique: we use another virus (here, a chimpanzee adenovirus) that we modify to transport genetic material capable of fighting Covid-19 into our cells.

According to several experts who commented on these results, too strong a first dose of vaccine could in fact make the immune system fight against the virus used as a carrier, contrary to the desired effect. This point will have to be clarified in the rest of the tests. Finally, the Russians from the Gamaleia Institute assured on November 11 that their vaccine was 92% effective. But they are based on a very small number of patients (only 20).

What is the most effective?

It is impossible to say at the moment, especially since all these results were announced only by press releases, without a detailed scientific publication. However, despite the seemingly lower efficacy figures, experts believe that the AstraZeneca / Oxford vaccine could have an additional benefit.

"Unlike other trials, the Oxford / AstraZeneca team screened all participants weekly for asymptomatic infections," commented Professor Eleanor Riley (University of Edinburgh), quoted by the UK Science Media Center.

In fact, one of the main questions is whether these vaccines block the transmission of the virus, in addition to reducing the severity of the disease in those who have received them. "We have initial indications that this vaccine may reduce the transmission of the virus, as a decrease in asymptomatic infections has been observed," Oxford University said in a statement.

However, all these data are only preliminary. "The differences in efficacy are based on the analysis of 100 to 200 patients out of a total of 30,000 to 50,000 volunteers for each vaccine, so these numbers can vary greatly thereafter," warned another expert, Dr. Julian Tang (University of Leicester), cited by Science Media Center.

Effective, but in whom?

Many other questions that they did not answer. First, we do not know how long these vaccines protect. So, it is not known if its action is identical in the populations at higher risk, starting with the elderly. They are much more likely to have a severe form of Covid-19, so it is critical that a vaccine be effective in this population group.

Pfizer / BioNTech said that the efficacy of its vaccine was "greater than 94%" for those over 65 years of age. But due to lack of publication in a scientific journal, we do not know the details. AstraZeneca and the University of Oxford, on November 19, published results in the prestigious medical journal The Lancet: they show that their vaccine elicits an immune response in older subjects (over 56 years of age) identical to that which it triggers in younger subjects (18 to 55 years).

However, these published results do not refer to phase 3 but to the previous phase, phase 2: the total number of volunteers is much lower (560 versus 23,000) and they are not representative of the general population.

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