RA-COVID-19 V6 - Recherche - Action Coronavirus disease 2019 - Vague 6

Development of SARS-CoV-2 vaccines – DC-CoVaC

Submission summary

Résumé: SARS-CoV-2 is a betacoronavirus that has recently emerged as a human pathogen in the city of Wuhan in China’s Hubei province. The disease caused by this newly identified virus has been named COVID-19 and symptoms include fever, severe respiratory illness and pneumonia. As of March 2020, the World Health Organization (WHO) has declared that SARS-CoV-2 is pandemic, and the number of confirmed cases is exponentially increasing. SARS-CoV-2 virus is closely related to SARS-CoV, which was responsible for the Severe Acute Respiratory Syndrome (SARS) in 2002. Similarly, to SARS-CoV, SARS-CoV-2 is of zoonotic origin and was demonstrated to cause life-threatening diseases in humans. So far, there is no vaccine or treatment for COVID-19. It is therefore critical to generate vaccines and drugs that will either prevent or treat COVID-19. At present, there are 8 candidate vaccines in clinical evaluation and more than 100 candidate vaccines in preclinical evaluation. Vaccine in clinical trials are represented by inactivated SARS-CoV-2 virus, non-replicating viral vectors, DNA and RNA vaccines (https://www.who.int). Surprisingly, no protein subunit vaccine are reported to be tested currently in clinical trial, as proposed in this project, which are generally safer and easier to produce. Moreover, all Human coronaviruses enter their host cells using the trimeric transmembrane spike (S) glycoprotein. The coronavirus’ S protein represents a major target for the human humoral immune response following SARS-CoV-2 infection. However, a large set of data from previous SARS-CoV-1 or CoV-2 infected individuals, or generated in preclinical models, pointed out the potential protective effect of cellular immunity. In this study, we propose to test the immunogenicity and the preventative effect of a combination of two vaccine platforms already in phase 1 to 3 clinical development; i.e the DNA-derived DREP platform and the anti-Dendritic cell (DC) targeting epitope-based vaccine. A series of DREP and DC-targeting constructs against SARS-CoV-2 are already available. A large set of data showed that these vaccines, either administered alone, or in a prime boost combination, elicited strong and durable T and B-cell immune responses against infectious agents. We develop here an original strategy aimed to induce a polyepitopic T and B cell responses. These vaccines are ready to be tested in two preclinical models, in humanized mice (mice reconstituted with a human immune system), allowing to study in depth human immune responses of different vaccine combinations, and in transgenic knock-in mice expressing the human CD40 and human ACE2, the receptor of SARS-CoV-2 to demonstrate the protective effect of these vaccines. The overreaching goal of this study is to identify within the 12-months time line of this project, vaccine (s) that will be moved forward to the clinical development.

Project coordination

Véronique GODOT (Institut Mondor de recherche biomédicale)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IMRB Institut Mondor de recherche biomédicale
Karolinska Institutet
CIPHE Centre d'immunophénomique

Help of the ANR 149,904 euros
Beginning and duration of the scientific project: September 2020 - 12 Months

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