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Preclinical study sheds light on a new vaccine candidate for Covid-19

A new international study, published in Cell, co-leaded by IDMIT (CEA-Jacob) and the Department of Medical Microbiology of the University of Amsterdam, presents the results of preclinical trials of a new protein vaccine candidate against Covid-19. This study shows that this vaccine candidate induces strong immune responses in the animal models used. Non-human primates (NHP) vaccinated and then experimentally infected with SARS-CoV-2 were preserved from the characteristic lung lesions of the disease and had a greatly reduced viral load in the upper respiratory tract and lungs.

Published on 8 March 2021

​For more than a year now, the Covid-19 pandemic has been raging, and vaccination is the best strategy for limiting the circulation of the virus and preventing severe forms of the disease. The vaccine race has begun, and more than 250 vaccine candidates1 are currently undergoing preclinical and clinical evaluation, including three currently approved in France.

Vaccination is based on the inoculation of the whole pathogen (the virus) in a harmless form into the host organism, or of a part of the pathogen: the host immune system will trigger an immune response allowing the production of specific antibodies that will be ready to neutralize the virus when it is actually in contact with the organism. It is not the pathogen as such that triggers the immune response, but specific proteins of the virus, the antigens. In particular, those on the surface of the virus are the key since they are essential for it to penetrate the cell. In coronaviruses and more specifically in the SARS-Cov-2 virus responsible for Covid-19, the "S" protein (for Spike) is the main antigen of interest: it is the main target of the neutralizing antibody response.

Current vaccine strategies exploit different "technological" platforms: live attenuated or inactivated vaccines, protein vaccines, DNA or mRNA vaccines, vectorized vaccines with replicative or non-replicative vectors, or pseudo-viruses.

In an international collaboration co-leaded by IDMIT and the Department of Medical Microbiology at the University of Amsterdam, a study published in Cell presents the synthesis and characterization of a novel protein vaccine candidate composed of nanoparticles carrying several Spike (S) proteins of the SARS-CoV-2 virus. Each vaccine particle is composed of twelve nanoparticles coupled to twenty Spike proteins, all stabilized by ionic polarizations. This assembly induces a stronger stimulation of the immune system.

Immunization studies have been performed in different animal models and have shown that this new vaccine candidate induces high levels of antibodies. The vaccine was then administered to non-human primates (NHPs) who were then infected with SARS-CoV-2. Different parameters were analyzed to report the efficacy of the vaccine. HNPs infected with SARS-CoV-2 and vaccinated had a strong and rapid reduction of viral load in the upper and lower respiratory tract. This protection is associated with the neutralizing antibody response, as well as the vaccine-induced cellular response. Vaccinated HNPs were preserved from lung damage in unvaccinated and infected control HNPs.

One year after the emergence of the virus, vaccination campaigns have started since a few weeks with vaccines, some of which present rather complex storage and logistic conditions. This first generation of vaccines allows us to fight against the progression of the pandemic, but questions remain open as to their effectiveness on secondary transmission between individuals, or the duration of the protection obtained. The need to develop new vaccines is therefore necessary to better control the reduction of the viral load, the contagiousness between individuals and also to satisfy an important demand in number of doses at the global level.

The results of this study present a new vaccine candidate using nanoparticle technology to more effectively solicit the body's response. This new approach holds promise in this time of health emergency and could be applied to other vaccine research, notably against HIV. 

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