A vaccine against Covid-19 for early 2021, it is possible

All over the world, public research teams and industry are working on the development of a vaccine against Covid-19. To take stock, we interview Marie-Paule Kieny, virologist, research director at Inserm, she is president of the Covid-19 Vaccine committee set up by the Ministries of Research and Health, to assess the candidates- vaccine.

The Conversation: What are the roles of the Covid-19 Vaccine Committee?

Marie-paule kieny : In the race against time to develop a vaccine against Covid-19, 198 candidates are in the running. Not all are at the same stage of development, most (154) are still at early stages of development. Some are in phase I clinical trials, corresponding to the first administration to humans and during which its safety is verified in a few dozen people, others in phase II, during which their ability to induce an immune response is tested in a few hundred volunteers. And finally, 10 are currently in phase III, to study their effectiveness and identify possible side effects with many more participants: generally around a few tens of thousands.

Monitoring the development of research is one of the committee's missions. Covid-19 vaccine that I chair. This group of 11 people aims to produce recommendations for the clinical assessment center network. COVIREIVAC to prioritize the clinical trials to be carried out in France, as well as to the government, which can take them into account when deciding which vaccine to pre-order or buy for the French population.

While our scientific opinion is of course very important, the political decision will also be based on the availability of doses, their price and on the confidence that buyers have in the producer.

TC: What are the most promising vaccine candidates?

M.-PK : Our follow-up of scientific publications and our meetings with industrialists focus in particular on the 10 most advanced candidates currently in phase III clinical trials. They are Chinese, American or European.

If the technologies - often called platforms - used in these different projects are not the same, which implies that the nature of the vaccine obtained will be different, the principle remains the same: it is a question of injecting all or part of the virus in order to generate a protective immune response. If the vaccine is effective, our immune system will recognize this foreign body and produce antibodies and "killer" T cells, which will allow it to react quickly if it comes into contact with the "real" virus, preventing its proliferation. and therefore disease.

Of the ten vaccine candidates tested in phase III, three are based on an inactivated virus, i.e. they contain the SARS-CoV-2 coronavirus, which has been treated with chemicals to cause it to lose its vitality. ability to reproduce. These vaccines are developed by Chinese industries and universities.

Two other of the most advanced candidates, developed in the United States and Europe, use the genetic material of SARS-CoV-2: RNA. This is used to produce proteins which will be used in particular to build new viral particles. The idea is to inject a fragment of the SARS-CoV-2 RNA into our cells. These will produce certain coronavirus proteins that our immune system will recognize, causing an immune response. Now "educated", the immune system will react when it encounters the whole virus.

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The last five vaccine candidates use adenoviruses, kinds of “non-replicating shuttle viruses” which, once administered to the vaccinated person, will produce certain SARS-CoV-2 proteins, which will be detected by our immune system.

It is still too early to decide on the best technology, and France intends to buy a portfolio of different vaccines in order to maximize the chances of having an effective vaccine.

With 10 candidates in phase III, I am reasonably confident that a vaccine will be available in early 2021, in low quantities to begin with. Indeed, the first results of phases III are expected before the end of 2020, and others could be announced in the months that follow.

TC: How effective will the vaccine be?

M.-PK : The perfect vaccine would be the one that would ensure a 100% effectiveness rate against infection with the SARS-CoV-2 virus: with such a vaccine, anyone vaccinated would be protected against Covid-19. She would not get sick from contact with the virus, nor could she pass it on.

In reality, it is much more likely that the efficacy rate does not approach 100%, and that some vaccinated people can transmit the SARS-CoV-2 virus without being sick. What to do in this case? The vaccination strategy will have to be adapted. The people in whom this rate will be particularly scrutinized are those over the age of 70, quite simply because they are most often victims of serious forms. They are therefore the ones to be protected.

One of the barriers that we encounter when vaccinating the older sections of the population results from a perfectly natural constraint called “immunosenescence”: as we age, our immune systems also age. In doing so, it becomes less responsive to vaccinations.

If the vaccine were to prove more effective in young people, one solution could be to vaccinate the relatives of the elderly.

The good news is that several vaccines have shown, in preliminary trials, a similar ability to induce an immune response, regardless of the age group considered. This parameter will have to be confirmed during trials on a larger scale.

TC: Are we naturally immune after coming into contact with the virus?

M.-PK : The very concept of a vaccine is based on our immune memory. Indeed, after a first exposure to a pathogen, our body keeps the memory of the infection, which makes it capable of reacting in the event of a second attack. Vaccination exploits this phenomenon: the injection of part of a given virus in anticipation of a subsequent encounter with this aggressor must allow our immune system to react effectively from the first contact with the real pathogen.

In our country, according to Public Health France, approximately 900 cases of infection with the SARS-CoV-000 coronavirus have been identified. Can we consider that these people are immune for life? Unfortunately it is not that simple.

SARS-CoV-2 appears to induce weak immune responses, that don't last very long. This is the case with other coronaviruses, such as those responsible for colds, which can infect us several times. The level of response also appears to correlate with the degree of severity of Covid-19 symptoms. An asymptomatic person usually has a weaker immune response than a person with mild symptoms, who in turn develops fewer antibodies than patients who had to be admitted to intensive care.

There are around ten scientifically documented cases of people having been infected twice. Some of these people did not develop symptoms during their second infection, but others had Covid-19. This figure is, for the moment, very low compared to the number of patients, but it is an indicator to follow.

TC: Will it be necessary to be vaccinated every year?

M.-PK : Certain pathologies, such as the flu or colds caused by mild coronaviruses, are seasonal. In this case, each year the virus circulates more in the population in winter. This may be related to the virus itself, which can survive longer under certain weather conditions, but especially our behavior. Indeed, in winter, we live more inside houses, in closed spaces, so close contact with other people is more frequent than in summer when we spend more time outside.

Is this the case for SARS-CoV-2? It's still too early to tell, as the latter only emerged last year.

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On the other hand, it is now well documented that SARS-CoV-2 mutates, and that its genetic heritage is not the same depending on the geographic region. Does this mean that it will also be necessary to develop the vaccine and renew the vaccination each year as for the flu? Not necessarily, because these mutations have not yet produced very different viral strains and the antibodies induced by the vaccine candidates seem to have the same efficacy in the laboratory with respect to the different strains.

TC: Does the speed of the search interfere with security?

M.-PK : If a question is essential in the development of a vaccine, it is the criterion of its harmlessness. This is first verified during phase I in a small number of individuals. Then, we move on to phase II to verify that the vaccine induces the type of immune response expected. Finally, we move on to phase III to verify that the vaccine is effective. To save time, these three phases are carried out in parallel for the candidate vaccines against Covid-19, but with the same rigor. All the classic criteria are met, and a vaccine with major side effects will not be marketed. This work is carried out by industrialists or public research teams, which is then verified by European and then French health authorities.

Marie-Paule Kieny, Research Director, Inserm

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