A mRNA Vaccine Encoding for a RBD 60-mer Nanoparticle Elicits Neutralizing Antibodies and Protective Immunity Against the SARS-CoV-2 Delta Variant in Transgenic K18-hACE2 Mice

Pascal Brandys (1) , Xavier Montagutelli (2) , Irena Merenkova (1) , Güliz T Barut (3) , Volker Thiel (3) , Nicholas J Schork (4) , Bettina Trüeb (3) , Laurine Conquet (2) , Aihua Deng , Aleksandar Antanasijevic (5) , Hyun-Ku Lee (6) , Martine Valière (1) , Anoop Sindhu (7) , Gita Singh (6) , Jens Herold (1)

1 Phylex BioSciences
2 Génétique de la souris - Mouse Genetics
3 University of Bern
4 TGen - The Translational Genomics Research Institute
5 The Scripps Research Institute [La Jolla, San Diego]
6 Abeomic
7 Aldevron GmbH

Two years into the COVID-19 pandemic there is still a need for vaccines to effectively control the spread of novel SARS-CoV-2 variants and associated cases of severe disease. Here we report a messenger RNA vaccine directly encoding for a nanoparticle displaying 60 receptor binding domains (RBDs) of SARS-CoV-2 that acts as a highly effective antigen. A construct encoding the RBD of the Delta variant elicits robust neutralizing antibody response, and also provides protective immunity against the Delta variant in a widely used transgenic mouse model. We ultimately find that the proposed mRNA RBD nanoparticle-based vaccine provides a flexible platform for rapid development and will likely be of great value in combatting current and future SARS-CoV-2 variants of concern.

Keywords: SARS-CoV-2; delta variant; mRNA vaccine; nanoparticle; receptor-binding domain; neutralizing antibody; K18-hACE2

Domains: Life Sciences [q-bio]; Immunology; Vaccinology

Pascal Brandys, Xavier Montagutelli, Irena Merenkova, Güliz T Barut, Volker Thiel, et al.. A mRNA Vaccine Encoding for a RBD 60-mer Nanoparticle Elicits Neutralizing Antibodies and Protective Immunity Against the SARS-CoV-2 Delta Variant in Transgenic K18-hACE2 Mice. Frontiers in Immunology, 2022, 13, pp.912898. ⟨10.3389/fimmu.2022.912898⟩. ⟨pasteur-03854887⟩