COVID-19 vaccine: too fast, too high, too strong?

Paris | It’s a global competition, quick like no other: in the race for the COVID-19 vaccine, the main thing is not to participate, but to be the first because the financial stakes are enormous. But watch out for announcement effects, dashed hopes and security issues.

• Read also: All developments in the COVID-19 pandemic

How many vaccines?

In its last point dated October 2, the WHO lists 42 “vaccine candidates” evaluated in clinical trials on humans around the world (against 11 in mid-June).

Ten are at the most advanced stage, phase 3, where the effectiveness of the vaccine is measured on a large scale, on tens of thousands of volunteers spread over several continents.

Among them, that of the American company Moderna, the German-American alliance BioNTech / Pfizer, several Chinese laboratories, a European project led by the University of Oxford (in cooperation with the company AstraZeneca) or the Spoutnik vaccine. V, developed by Russia and its Gamaleïa research institute.

The others are still in phase 1 (which primarily aims to assess the safety of the product) or phase 2 (where the question of efficacy is already being explored).

In addition to the trials that have already started, the WHO counts 151 candidate vaccine projects in the pre-clinical development phase.

What techniques?

There are different approaches, based either on proven vaccine categories or on more innovative techniques.

Some teams are working on conventional types of vaccines that use a “killed” virus: these are “inactivated” vaccines (such as those from the Chinese Sinovac and Sinopharm).

There are also so-called “subunit” vaccines, based on proteins (antigens) that trigger an immune response, without viruses.

Other vaccines, known as “viral vector” vaccines, are more innovative: another virus is used as a support that is transformed and adapted to fight Covid-19.

This is the technique chosen by the University of Oxford and the Russians, which use adenoviruses (a family of very common viruses).

Finally, other innovative projects are based on “DNA” or “RNA” vaccines, experimental products using pieces of modified genetic material. This is the case for those of Moderna and BioNTech / Pfizer.

“The more candidates we have with different techniques, the more likely we are to end up with a vaccine that works and is well tolerated,” Daniel Floret, vice-president of the technical committee for vaccinations, told AFP. French High Authority for Health (HAS).

What results?

For the moment, only preliminary results (phases 1 and / or 2) have been published in scientific journals. The latest, published on September 4 in the journal The Lancet, are that of the Russian vaccine.

Others were released this summer, concerning vaccines from the University of Oxford, Chinese CanSino or Moderna.

Overall, these results are considered encouraging and show that the vaccines in question elicit a good immune response.

However, it is far too early to draw any conclusions.

To be fixed, “it is necessary that the phase 3 trials go to their end and that we not base the analysis on intermediate results, as well on the questions of safety as of efficacy”, told AFP immunologist Alain Fischer.

This is all the more true as many unknowns hover over the mechanisms of immunity against Covid-19, with a few cases of reinfection starting to be reported.

Always faster?

All over the world, procedures have been speeded up in unprecedented ways. And a distant battle between China, the United States of Donald Trump and the Russia of Vladimir Putin.

In early August, Vladimir Putin had trumpeted that his country had developed the first vaccine against Covid-19, even before the publication of preliminary results and the entry into phase 3.

Donald Trump, he hoped that a vaccine would be authorized before the US presidential election on November 3.

But in early October, the United States Medicines Agency (FDA) set criteria for the duration of the trials that make a conclusion materially improbable in the coming weeks. This pleasantly surprised the most critics of the experts, who thought the FDA would give up.

From an economic point of view, international fundraisers have been launched by states and large foundations. This allows companies to set up the industrial process of manufacturing their vaccine at the same time as they work on its development, usually two distinct stages.

“What is different with vaccines against Covid-19 is that the development and potential approval times are much faster because of the public health emergency,” explains the European Medicines Agency ( EMA) on its website.

Speed ​​versus security?

“The safety requirements for vaccines against Covid-19 are the same as for others and will not be lowered due to the pandemic”, assures the EMA.

Because going too fast in clinical trials “can pose a problem” in terms of safety, underlines Daniel Floret.

“Everyone wants a vaccine to be available in good conditions as quickly as possible, but we must not confuse speed and haste: we must give ourselves the time for a complete, rigorous and transparent analysis”, insists Prof. Fischer.

Two Phase 3 trials have been put on hold in recent weeks for safety reasons.

At the beginning of September, the one in Oxford / AstraZeneca was interrupted due to an unexplained illness in one participant. It picked up after a few days in the UK and other countries, but not in the US.

Monday, the pharmaceutical group Johnson & Johnson in turn announced the suspension of its trial, again “due to an unexplained illness”.

In both cases, the trial was suspended to see if these diseases were related to the vaccine or something else. This is why these interruptions should not be seen as bad news, but on the contrary as a reassuring point, according to the experts.

“This shows that the process of monitoring the safety of participants is working well, which is a reason for confidence”, judge Professor Stephen Evans (London School of Hygiene & Tropical Medicine), quoted by the British organization Science Media Center ( SMC).

To reconcile speed and safety, the EMA has set up an accelerated procedure: it allows it to examine the safety and efficacy data of vaccines as and when they are published, even before a formal request for it is made. authorization is filed by the manufacturer.

Two vaccine projects have been subject to this “continuous review” since early October, those of Oxford / AstraZeneca and BioNTech / Pfizer. Moderna hopes to become the third soon.

When will a vaccine be available?

“We do not know if vaccines against Covid-19 will be approved and how long it will take, because it is difficult to foresee a timetable”, advances the EMA cautiously.

But some pharmaceutical companies, who have an economic interest in saying it, swear it’s possible before the end of 2020.

“I think that there, yes, we are going a little too fast”, commented Monday on the LCI channel the epidemiologist Arnaud Fontanet, member of the Scientific Council which guides the French government.

“There are regulatory approvals, production, all that has to follow. So second half of 2021, for me at best, ”he said.

At the beginning of September, the WHO had indicated that it did not expect a general vaccination against Covid-19 before mid-2021.

“If we get there by this deadline, it will already be a sacred wonder”, while it usually takes several years, adds Daniel Floret.

And in the worst-case scenario, you may never be able to develop a vaccine.

What vaccine against mistrust?

Even if the research leads to a more or less long term, there will remain a final question, of size: will people accept to be vaccinated, in a context of growing distrust?

According to a study published Wednesday in the British journal Royal Society Open Science, a not insignificant part of the population of some countries believes in conspiracy theories on Covid-19, which increase mistrust of vaccination.

For example, the false claim that the pandemic “is part of a plan to impose global vaccination” is believed to be reliable by 22% of Mexicans polled for this study.

These false theories are propagated on social networks.

“Governments and tech companies should look for ways to improve digital media literacy among the population. Otherwise, developing a vaccine might not be enough ”, commented one of the authors of this study, Sander van der Linden, researcher in social psychology at the University of Cambridge (England).