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COVID-19 and immunology – ways forward towards new vaccination strategies for novel viruses

Elsa Champion
04/23/2020
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Four questions for Nicolas Manel, Inserm Research Director at Institut Curie’s Immunity and Cancer unit
Nicolas Manel

Nicolas Manel

Could you give us an overview of the COVID-19 virus?

As with the viruses behind SARS (Severe Acute Respiratory Syndrome), which emerged in China in 2002/2003, and MERS (Middle East Respiratory Syndrome), which emerged in 2012/2013, SARS-CoV-2 (the virus strain behind COVID-19) is a novel virus that belongs to the coronavirus family. These viruses are spherical and feature ‘spike’ proteins on their surface, which look like crowns under the microscope – hence their name. Virologists are very familiar with coronaviruses, as they are widespread in the animal kingdom. Just as with SARS and MERS, SARS-CoV-2 originated in a natural host species: bats. SARS-CoV-2 then randomly ‘jumped over’ to an intermediate host species (pangolin), and then, as a result of a similarly random adaptation, contaminated humans. This is the root cause of the pandemic we are currently experiencing.

SARS-CoV-2 is transmitted via droplets or secretions and causes benign disease in most people. The latest figures show that 90% of people show no symptoms. Among the remaining 10% who do have symptoms, only a tiny percentage report very severe pulmonary symptoms (as the viruses destroy lung cells) that can then lead to respiratory insufficiencies and ultimately potentially even death.

The main distinguishing feature of SARS-CoV-2 lies in the manner in which it is transmitted. It is spread during its incubation phase, when people show no symptoms of the illness, and therefore have no idea they are infected. This is a big difference compared to SARS and MERS, where people only became contagious when they became ill. We can’t explain this new form of transmission, but this is the primary explanation for the scope and scale of this pandemic.

How close are we to finding a vaccine for COVID-19?

SARS-Cov-2 is an emerging virus: nobody has ever been exposed to it before, and so nobody has developed ‘memory’ immunity. This means we have no vaccine for COVID-19, and that is what is causing the global public health crisis.

The virus appeared in December of last year, and teams rushed to start developing a vaccine. Today, around fifty different vaccines around the world are currently being made and tested, and in some cases even undergoing clinical trials. But we know that the traditional routes to developing confirmed vaccines take around 18 months. The time needed to design, make and test vaccines is incompressible. The (relatively) good news with respect to this virus, is that it is very genetically stable (compared to HIV, for example) and the vaccines currently in development should remain effective for several months, and potentially even years. We can expect waves of this virus to follow, and for the waves to come, we will have a vaccine that should allow us to contain the epidemic.

You are currently working on ground-breaking vaccinology technologies. Might these apply to COVID-19?

My team and I are exploring new methodologies for designing new types of vaccines that will be faster and more effective than those developed using traditional tried-and-tested processes. Based on Institut Curie research, a few years ago we lodged a Curie-Inserm patent application for a new vaccinal platform. In a continuation of this, in 2015 we co-founded a start-up with Sylvain Carlioz, which works in collaboration with Institut Curie: Stimunity (www.stimunity.com), designed to develop cancer vaccine projects.

This platform is based on the fact that we succeeded in taking inactivated virus particles, and adding a natural immunomodulator (which plays an adjuvant role): cGAMP, a molecule that occurs in cells capable of powerfully triggering immune responses. It’s a bit like a Trojan horse: the virus is the horse, complete with all the proteins we’re trying to vaccinate against, and then inside, we’ve slipped the cGAMP, which will trigger immune responses.

For the time being, we’re focusing on cancerology projects, but we could deploy our technology to tackle infectious diseases, too. One of the biggest challenges in the years to come will be developing a full arsenal of different vaccines to combat novel viruses. With this in mind, we’re investigating the idea of extending our platform into a coronavirus project and validating use of our method for other related viruses.

How can your work on cancer help deepen understanding of COVID-19?

Along with my colleague Matthieu Piel, head of Institut Curie’s Systems Biology of Cell Polarity and Cell Division, we’ve been working on cancer for a long time now and we’re running basic research projects into understanding how the immune system ages. In effect, a huge number of cancers are age-related (lung cancer, breast cancer, etc.). Some risk factors such as genetic mutations are linked to age, but that’s not the only reason why cancer develops. A number of other mechanisms come into play with cancer, which we still don’t understand.

Consequently, we developed animal models to test different mechanisms linked to the immune system, and with respect to the lungs, some interesting findings emerged. When the COVID-19 epidemic started, age emerged as a crucial factor. The older a person is, the more severe their symptoms. In SARS-CoV-2 infections, there is a clear age-related risk factor that we don’t understand. Considering the nature of our work and our earlier findings, I and my colleague Olivier Schwartz from Institut Pasteur launched a project we are currently testing in the laboratory. This makes perfect sense from Institut Curie’s perspective: biologically speaking, SARS-CoV-2 infections and the development of cancer share common mechanisms. This means that understanding the coronavirus is important in the fight against cancer.