Covid-19: the reasons for the failure of the CureVac vaccine candidate

The candidate vaccine has been put away in the closet. The German laboratory CureVac announced on Tuesday the abandonment of the development of its first serum against the coronavirus, initially a source of hope, but whose effectiveness has been disappointing. But the company on the other side of the Rhine has not had its last word and wants to focus on a more promising new vaccine. “The global fight against Covid-19 continues and we are determined to make a decisive contribution to it with a safe and effective vaccine,” but “the requirements for an effective fight against the virus and the variants that appear have changed,” explained Franz. . Werner Haas, head of CureVac, in a statement. Behind this statement, the admission of a failure that can be explained by several factors.

Before the summer, Europe is still betting on the Curevac vaccine. Until the disappointing final results of its large-scale clinical study, released in early June, showing an efficacy of only 48%, a much lower rate than other mRNA vaccines from the Pfizer / BioNTech and Moderna alliance. At that time, the head of CureVac tries to justify himself by stating that the effectiveness of the serum varies according to the age group and the viral strains and that, therefore, it is “difficult to obtain a high effectiveness. With this unprecedented range of variants.” . Despite this result, CureVac said at the time that it was convinced that its vaccine candidate “makes a valuable contribution to public health by fully protecting study participants between the ages of 18 and 60 against hospitalization or death.” , according to its CEO Franz-Werner Haas.

But the problem seems deeper since the failures of this serum against Covid-19 are due more to its structure. This is because CureVac’s candidate vaccine differs from its rivals Pfizer and Moderna in several respects. First difference, the type of RNA used is not the same. The German firm has chosen to work with a more natural RNA unlike BioNTech and Moderna who have decided to chemically modify the constituent elements (called nucleotides) of their RNA. Consequences: the RNA used by CureVac presents more difficulties to enter the cells, “which implies a lower production of peak proteins and, ultimately, a lower production of antibodies against the coronavirus”, underlines the specialized medium Sciences et Avenir .

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An underdosed vaccine

Another difference between CureVac and its American counterparts: the RNA dose is not the same either. Compared to other sera, the CureVac candidate vaccine is too low a dose. In the weekly Die Zeit, Peter Kremsner, director of the Tübingen Institute of Tropical Medicine, which is involved in the CureVac study, agrees. In German serum, the active substance is 12 micrograms per vaccine dose. By comparison, it’s 30 micrograms in BioNTech and 100 in Moderna. However, the scientist points out that it is impossible to increase the dose of the CureVac vaccine at the risk of seeing side reactions that are too strong.

CureVac’s Covid-19 vaccine is now the seventh to be phased out after clinical trials. Last month, Sanofi announced that it was giving up its mRNA vaccine. Founded in 2000 by researcher Ingmar Hoerr, a pioneer in messenger RNA research, CureVac was one of the first biotech companies to embark on the vaccine race. The abandonment of CureVac’s candidate vaccine “puts an end” to the pre-order agreement of 405 million doses with the European Union, specifies the laboratory, which nevertheless continues discussions with Brussels on the second generation of vaccine.

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The company specializing in messenger RNA will “focus on the development of a second-generation vaccine against Covid-19” in which it is working with the British GSK and will therefore “withdraw” the current candidate from the continuous review procedure by the European Medicines Agency (EMA). CureVac and GSK want to launch “in the coming months” the clinical study on the second-generation vaccine, which takes more into account the variants, for approval “in the course of 2022”. An authorization for the first vaccine would also have been likely “at the earliest in the second quarter” of next year, according to the statement.

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