10:45 p.m., January 23, 2021
Former CEO of Inserm, doctor Yves Lévy, director of the Vaccine Research Institute (VRI) at CHU Henri-Mondor in Créteil (Val-de-Marne), is an immune system specialist. For a year, he has been in the race for the vaccine against the Covid-19. Like other immunologists around the world, he fears that the virus will take hold.
Read also – Covid-19: we take stock of the new variants and their presence in France
Is the appearance of the English, South African or Brazilian variants surprising?
On the contrary, random mutations are common phenomena. A virus is a photocopier that multiplies billions of times in the body. In doing so, he makes mistakes. Either they are unfavorable to it and the variant virus declines. Either they are favorable to it, and its contagiousness – and / or its dangerousness – increases. The purpose of a virus is simply to survive; to survive at best. It’s a relentless Darwinian mechanism: the most efficient mutants end up gaining the upper hand. The Sars-CoV-2 that hit us in March was already a more contagious strain than the one detected in China.
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The immune system, which defends us, allows the virus to escape
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But why are so many more contagious mutants popping up today?
The more the virus circulates during an epidemic, the more the number of affected people increases, the more the risk of mutations increases. Our body tries to control the virus by developing an immune response. For its part, the virus is trying to escape him. By spreading very widely and very quickly on the planet, Sars-CoV-2 faces millions of antibodies, these small missiles that try to prevent it from entering the body. If he succeeds in breaking through this first defense, he still has to face a second line of killer cells directed against the infected cells. It is in this hostile environment for him, and because of these multiple interactions between him and us, that selection pressure is exerted. To force the lock and succeed in crossing these obstacles, Sars-CoV-2 has most often mutated, until now, at the level of the Spike protein, that is to say right at the place that allows it to enter our cells. If, for example, the variants identified in the UK and South Africa have mutations in common, it is because the immune response common to all individuals is directed against this region of the virus. There is a paradox here: the immune system, which defends us, allows the virus to escape. This exhaust is its survival. The goal of a vaccine is to induce an early, stronger and more lasting response to counter this phenomenon.
Read also – Virologist Bruno Lina on variants: “Nobody knows when Covid-19 will stop mutating”
So many changes, is it unprecedented?
On the contrary, it is very banal and reminds all those who fought against AIDS in the 1980s and 1990s of the confusion and despair that reigned then. When the first antiretrovirals arrived, drugs that could not completely block the replication of the virus, mutants appeared in the patients. Sometimes in just eight days! The search for new drugs was aimed at countering these mutants: it was necessary to develop dual therapies and then triple therapies, which are fortunately effective today.
Do variants make vaccines ineffective?
The absolute urgency is to vaccinate the most vulnerable with the vaccines available to protect them against the disease. As the antibodies induced by these products are directed against different regions of the virus, one can think that they will remain partly effective. An article has just shown that the antibodies induced by the Pfizer-BioNTech vaccine could neutralize the English mutant in the laboratory. It might be less true with the South African variant. However, this poses the long-term question of the need to adapt vaccines to mutations that have already appeared or are to come. We must therefore be prepared for the possibility of having to revaccinate on a regular basis. And so, no doubt, to develop new vaccines, as we do every year for influenza. At VRI, we are working on second-generation vaccines that already include mutations of current variants in order to induce, at the same time, antibodies and killer cells, the body’s second line of defense. We hope for a protective effect in the long term.
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It is urgent to open production lines and develop new vaccines to revaccinate if necessary and counter the variants.
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In Provence, virologist Jean-Michel Claverie says that slow, non-massive vaccination can promote the emergence of variants. Does that worry you?
The demonstrated effect of the vaccines in use today is to prevent severe forms of infection. We do not yet have scientific proof that they decrease the transmission of the virus, although it is likely. Today, the main problem facing states is that of global production, insufficient to cover 7 billion people. Some complain about the delays in vaccination in our country; this required logistical efforts which must be welcomed. It could be recalled that the vaccine is a global public good and that in Africa less than 6,000 inhabitants have been vaccinated. However, the virus has no borders and will continue to circulate everywhere. It is urgent to open production lines and develop new vaccines to revaccinate if necessary and to counter the variants.
If the vaccine is not lastingly effective, how can group immunity be achieved?
The notion of “group immunity”, which would set in naturally after the virus has affected a large number of individuals and which would prevent its circulation, is illusory. This is what we can see today in Manaus in Brazil, where people are reinfecting themselves when 60% of the population had been previously infected. Group immunity has only been described after massive vaccination campaigns. And it often takes decades to achieve this with highly effective vaccines that induce long-term immunity. For lack of hindsight, we do not yet know, for Sars-CoV-2, how long the vaccines are effective.
Is Sars-CoV-2 a seasonal virus like the flu?
A year has passed and we have not seen it weaken, except during confinements. In South Africa, it circulates despite the southern winter; it was also very present in Israel in August… We do not find the seasonal variations of the flu.
How to block the arrival of the English clone?
Darwin’s lessons suggest that it is mission impossible. The massive spread of the virus has encouraged the appearance of more contagious variants, which will become the majority. We will not win the speed race against them but we can slow down their progress by trying to circumscribe the clusters, by testing, tracing and isolating. Containment remains the most effective weapon. You cannot overcome a fire by letting it burn! To hope to break this infernal cycle, let’s use all the other weapons at our disposal: wearing a mask, barrier gestures and of course vaccination. While it is not certain that it can end the epidemic, it will protect the most vulnerable and lift the pressure on the health system.
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Like nuclear weapons, the vaccine is also an issue of sovereignty
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Could more massive sequencing help us fight against variants?
It is said that France is under-funded in this area. This is wrong: our fleet of sequencers is sufficient even if it remains to organize a monitoring network and centralization of data. But sequencing all the time is useless. Detecting all people with a variant would only be of interest if it changed the medical care. However, we have nothing to suggest other than the isolation of cases. The important thing is to carry out surveys in order to be able to model the progression of the epidemic. And above all to identify clusters and carefully isolate affected people.
When will we return to normal life?
Policymakers should consider all scenarios, from the most optimistic to the most pessimistic, hoping that the latter do not materialize. I am wary of the magical thought that the virus will tire itself out in the summer and the vaccine will necessarily block the transmission of the epidemic, even if we all hope so. However, one must also be prepared for the hypothesis of a more pessimistic scenario whereby the virus would still circulate for several years. If so, we should learn to coexist with it; and already adapt with new weapons. I really hope I’m wrong, but we have to think about it, as a country equips itself with a nuclear shield wishing it would never be used. And like nuclear weapons, the vaccine is also an issue of sovereignty.
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