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); CARLOS PAVAN

Scientific Reports

Nature Research

Año: 2022

2045-2322

The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidateto develop effective COVID-19 vaccines since it can induce potent neutralizing antibodies. We havepreviously reported the highly efficient production of RBD in Pichia pastoris, which is structurallysimilar to the same protein produced in mammalian HEK-293T cells. In this work we designed anRBD multimer with the purpose of increasing its immunogenicity. We produced multimeric particlesby a transpeptidation reaction between RBD expressed in P. pastoris and Lumazine Synthase fromBrucella abortus (BLS), which is a highly immunogenic and very stable decameric 170 kDa protein.Such particles were used to vaccinate mice with two doses 30 days apart. When the particles ratio ofRBD to BLS units was high (6?7 RBD molecules per BLS decamer in average), the humoral immuneresponse was significantly higher than that elicited by RBD alone or by RBD-BLS particles with a lowerRBD to BLS ratio (1?2 RBD molecules per BLS decamer). Remarkably, multimeric particles with a highnumber of RBD copies elicited a high titer of neutralizing IgGs. These results indicate that multimericparticles composed of RBD covalent coupled to BLS possess an advantageous architecture for antigenpresentation to the immune system, and therefore enhancing RBD immunogenicity. Thus, multimericRBD-BLS particles are promising candidates for a protein-based vaccine.