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Coronavirus: France starts vaccine trials

France's first trials of a potential Covid-19 vaccine start this month at the Institut Pasteur in Paris. Connexion spoke to its scientific director Christophe d’Enfert.

France leads the way in the development of a Covid-19 vaccine

The Institut Pasteur, world-renowned for its work on infectious diseases since founder Louis Pasteur developed vaccines against illnesses including rabies in the 19th century, is now leading the way in France on a Covid-19 vaccine. France is also teaming up with three other EU countries to form an “inclusive vaccine alliance” to source vaccines for EU nations and placing an order for up to 400million doses of one particular vaccine being tested by Oxford University.

UK-based pharmaceutical giant AstraZeneca has pledged to supply that vaccine at cost price. It is already in human trials and may be available before the end of the year.

Is it correct you are ready to start human clinical trials this month (July)?

That’s right. This concerns one of our vaccine projects that is based on a measles vaccine that we have engineered to be used against the Covid-19 virus. We have been running animal experiments and are launching phase 1 clinical trials [with people] in France and Belgium in July. We know our vaccine is inducing production of antibodies, especially “neutralising” ones that can block the entry of the virus into cells, so this is encouraging and it suggests the vaccine is going to protect against infection. However, this needs to be demonstrated. We are now evaluating whether the vaccine is protecting against infection in mice.

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Where will trials be done in France?

They will be in Paris. There will be 45 people in France and 45 in Belgium. The goal of phase 1 is mostly to evaluate whether it is safe – whether there are side- effects – and we can increase the number of volunteers and proceed to phase 2. We will also use this phase to evaluate if there is an antibody response in humans. 

We expect to obtain the outcomes in October, then we will go to phase 2 and 3 trials with way more people. The aim of phase 2 is to evaluate the vaccine’s ability to produce an immune response and the aim of phase 3 is to test its efficacy. Phase 2 and 3 will be under the responsibility of MSD [a multinational US pharma company], especially Themis Bioscience [an Austrian firm acquired by MSD this year], who will commercialise the vaccine.

When might it be available?

We expect results of phase 2-3 in the first half of 2021. Then it’s a question of production capabilities. I understand Astra­Zeneca is organising production of its vaccine as soon as they have positive results and authorisation to commercialise, so I assume MSD is going along the same lines. We also have two other vaccine candidates for which we are discussing possibilities of launching a phase 1 trial.

Why is the measles one promising?

Firstly, the measles vaccine has been widely used without safety issues and with high efficacy against measles, and there is a great knowledge about how to produce it. There is also evidence it can work because there is a measles-derived vaccine for chikungunya in phase 3, developed by Themis, and they have one for the MERS coronavirus [identified in 2012 and which, WHO says, could cause a future pandemic].

There was also a measles-derived vaccine for the SARS virus that worked efficiently in animal tests. So there is evidence it can lead to new vaccines against a number of viruses, and we are optimistic it will be effective against Covid-19.

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How do you feel about France and other countries placing a large order for the Oxford vaccine?

The key thing is to eventually have one or several vaccines that can help us fight Covid-19. It could be several and you cannot in any case predict the outcome of all of the vaccine projects. There are around a dozen entering trials. The Oxford one may not work, so it makes sense to continue different projects in parallel.

AstraZeneca said it would supply it at cost price so it could be widely distributed. Will you do the same? 

Our vaccine was launched with support of the CEPI, a global coalition for vaccine development and response to epidemics. Different governments put money into it to support projects. France did not, even though CEPI is supporting us. One idea behind that is that if the vaccine is produced, it should be equitable and affordable for low-income countries. Even though phase 2-3 will be under MSD’s responsibility, they have agreed to continue with that.

You say the project is a collaboration, but did the Pasteur Institute originate it?

Dr Frédéric Tangy started developing this measles platform [vaccine available as a base for modification] here maybe 20 years ago and it has had different applications. Discussions with big vaccine companies can eventually end up with partnerships and one was signed with Thémis eight years ago, which has grown up for different applications, especially this one now for Covid-19.

Are you well prepared in case of new pandemic viruses emerging?

Yes, because we have this platform, and we know how it works. The first warning of the Covid-19 epidemic was at the end of December. The genome of the coronavirus was sequenced in January and the first genetic construct that we made to produce this new vaccine was obtained by mid-February.

Because you have this platform, as long as you know the antigen to use to produce a vaccine, you can be very fast and reactive in case of a new epidemic. The other reason we could react fast was SARS-CoV-2 [virus which causes Covid-19] was very similar to the SARS and MERS viruses, so we know it pretty well. If we were exposed to a totally unknown virus, it would change things. You would have to figure out the function of the different proteins encoded by the virus and which ones could be useful in developing a vaccine. This would take more time. However, now we know coronaviruses well and can go very fast.

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The impact in 2020 has been extraordinary. What was special about Covid-19 and might this happen again?

It’s hard to predict but there have been an increasing number of new epidemics in recent years, with emerging viruses every two to three years. The likelihood of another one in around three years is high. Whether it will be a pandemic, you cannot say.

With SARS [which mostly affected the Far East], it was fairly easy to isolate people. The difference then was that people would become contagious only if they had symptoms, and you could easily identify and confine them and limit the epidemic. It dropped very fast. In the case of SARS-CoV-2, unusually for this kind of illness, those without symptoms are already contagious, which is probably the reason it spread so fast across the globe.

Some people at Pasteur have done genome sequencing of isolates [samples of strains of the virus] collected in France and you see the virus was circulating here at the beginning of the year when nobody knew about it. It was spreading silently, then started blooming. Today, globalisation also has an impact on the way disease spreads. When you follow the isolates that have been collected, you clearly see the spread from China to Europe and the US. The fact people travel more is a reason why these viruses can spread so fast, but this is true for a number of other diseases as well.

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