Covalent coupling of Spike's Receptor Binding Domain to a Multimeric Carrier produces a high immune response against SARS-CoV-2

CONSORCIOARGENTINO ANTICOVID; D'ALESSIO, CECILIA (CO-CORRESPONDING AUTHOR)

Scientific Reports

Nature Research

Año: 2022

2045-2322

The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2is a promising candidate to develop effective COVID-19 vaccines since it caninduce potent neutralizing antibodies. We have previously reported the highlyefficient production of RBD in Pichiapastoris, which is structurally similar to the same protein produced inmammalian HEK-293T cells. In this work we designed an RBD multimer with thepurpose of increasing its immunogenicity. We produced multimeric particles by atranspeptidation reaction between RBD expressed in P. pastoris and Lumazine Synthase from Brucella abortus (BLS), which is a highly immunogenic and verystable decameric 170 kDa protein. Such particles were used to vaccinate micewith two doses 30 days apart. When the particles ratio of RBD to BLS units washigh (6-7 RBD molecules per BLS decamer in average), the humoral immuneresponse was significantly higher than that elicited by RBD alone or by RBD-BLSparticles with a lower RBD to BLS ratio (1-2 RBD molecules per BLS decamer).Remarkably, multimeric particles with a high number of RBD copies elicited ahigh titer of neutralizing IgGs. These results indicate that  multimeric particles composed of RBD covalentcoupled to BLS possess an advantageous architecture for antigen presentation tothe immune system, and therefore enhancing RBD immunogenicity. Thus, multimeric RBD-BLS particles  are promising candidates for a protein-basedvaccine.