The vaccine race is accelerating as the American biotechnology company Moderna announced after its phase 3 clinical trial that its vaccine against Covid-19 provided an efficacy of 94.5%. How does it work ? What are the differences with the Pfizer / BioNTech alliance vaccine candidate? Here is what you need to know.

How did the clinical trial go?

This phase 3 study, started in July and still ongoing, known as the COVE study recruited more than 30,000 participants across the United States and was conducted in collaboration with the National Institute of Allergy and Infectious Diseases, an organization belonging to the National Institutes of Health. The primary endpoint was the analysis of confirmed COVID-19 cases two weeks after a second dose of vaccine several weeks apart. This showed that out of 95 cases, 90 cases of COVID-19 were observed in the "placebo" group against 5 cases observed in the "vaccine" group, which established that the efficacy was 94 , 5% versus 90% for the Pfizer / BioNTech vaccine. The second criterion was to analyze the more serious cases of COVID-19: 11 cases occurred in the placebo group and none in the vaccinated group.

 A review of adverse events indicated that the vaccine was generally well tolerated and that the majority of adverse events were mild or moderate in intensity. Grade 3 (severe) events with a frequency of 2% or more after the first dose of vaccine included pain at the injection site and included, after the second dose, fatigue, muscle pain, arthralgia, headache and pain / redness around the injection site. The company said "as more cases accumulate before the final analysis, it expects the point estimate of vaccine effectiveness to change." She plans to submit all the study data to a peer-reviewed publication, knowing that the duration of protection conferred by the vaccine is not yet known.

The technology used: the RNA vaccine

Currently, there are several types of COVID-19 vaccines that are or will soon be the subject of large-scale clinical trials:

mRNA (nucleic acid) vaccines,
subunit vaccines (based on whole killed pathogens)
and vector vaccines (inject an inactivated virus).

For the three vaccine candidates from Pfizer / BioNTech, from the Sanofi laboratory, also in the running, and that from the American biotech Moderna (which bears the name mRNA-1273), the method chosen is the first. As the scientific journal The Conversation explains, "In the case of RNA vaccines, the principle is to produce fragments of infectious agents capable of stimulating the immune response directly by the patient's cells. (...) The idea is to inject the patient with RNA molecules corresponding to proteins of the pathogen against which it is desired to be immunized. "

Concretely, the principle consists in using a messenger RNA encoding the Spike protein of the SARS-CoV-2 coronavirus which causes COVID-19. Indeed, many studies have shown that the Spike protein, the "spikes" on the surface of the virus, is the key that allows SARS-CoV-2 to enter our cells, and is one of the targets of our system. immune to infection. Inserm specifies on this subject that following the complete sequencing of the virus genome, it was quickly possible to produce this key protein in the laboratory. With this type of vaccination, the body recognizes that the protein shouldn't be there and produces T lymphocytes and B lymphocytes, defensive white blood cells, which will remember how to fight the virus if infected. According to the Sanofi laboratory, this vaccination technique could allow the development of vaccines in indications for which vaccination was not a viable solution.

A method of conservation that is important

The conditions for long-term storage, shipping and distribution of a vaccine are very important from a logistical point of view to ensure its use worldwide. Thus, the potential vaccine from the Pfizer laboratory and its German partner BioNTech must be stored at -70 ° C, which in particular led France to obtain upstream 50 “super-freezers” to be able to store it, a very costly investment in terms of especially for poor countries. And this even if the vaccine in question can be stored at 2 ° C to 8 ° C in a conventional refrigerator for 24 hours before being administered. In the case of Moderna's vaccine, the company highlighted the fact that for shipping and storage, it must be stored at -20 ° C, which greatly facilitates these steps.

“Using standard freezing temperatures of -20 ° C is an easy method of distribution and storage, and most pharmaceutical distribution companies have the capacity to store and ship products at this temperature worldwide. », Says the company. It is after thawing, to facilitate storage at the administration points, that the vaccine can remain stable under standard refrigerated conditions of 2 ° to 8 ° C for up to 30 days, during its shelf life of 6 month. This allows “storage in most pharmacies, hospitals or doctors' offices. », Indicates Moderna, who specifies that once taken out of the refrigerator to be administered, the vaccine can be stored at room temperature for up to 12 hours. For its part, the Sanofi laboratory has announced that its vaccine against Covid-19 will not need to be stored in the freezer.
 What is the next step ?

 Based on these preliminary safety and efficacy data, Moderna has announced its intention to submit an emergency use authorization request to the Food and Drug Administration (FDA). in the coming weeks and expects its final safety and efficacy data to be expected in two months. It also wants to "submit authorization requests to global regulatory agencies." The company says it is "already working with the Centers for Disease Control and Prevention (CDC), a vaccine distributor hired by the US government as well as global stakeholders" to prepare for its vaccine distribution if it is approved.

By the end of 2020, the company plans to manufacture approximately 20 million doses that will be shipped across the United States and says it is ready to manufacture 500 million to 1 billion doses to ship worldwide as soon as possible. 2021. Finally, according to L'Express, the company has received $ 2.5 billion from the US government to develop the vaccine, and produce 100 million doses. It has also signed contracts with Canada, Switzerland, Japan, Israel and Qatar and is in negotiations with the European Union, the United Kingdom and the international Covax program. The market demand is expected, like its American competitor, within the next few weeks.