Chimeric monoclonal antibodies as a strategy for activation of immune responses against SARS-CoV 2 infection

• Grant number: 21/11971-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): April 01, 2022
• Status: Discontinued
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Silvia Beatriz Boscardin
• Grantee: Mariângela de Oliveira Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 24/02538-2 - Generation of human monoclonal antibodies against the infective forms of Plasmodium vivax, BE.EP.PD

Abstract

SARS-CoV-2 virus, the etiologic agent of COVID-19 triggers a severe acute respiratory disease that leads to death in approximately 2% of the cases. In such a fragile scenario that involves the need to invest in vaccine strategies, it is necessary to prioritize versatile and safe vaccine strategies. Several studies have demonstrated the great potential of immunizations based on strategies aimed at targeting antigens to Dendritic Cells (DCs). To explore this approach, this research project aims to evaluate the efficacy of recombinant monoclonal antibodies fused to the receptor binding domain (RBD) of the Spike protein of SARS-CoV-2, which are able to target the protein to subpopulations of DCs. To achieve this goal, the recombinant antibodies will be constructed, produced in eukaryotic system and purified by G protein affinity chromatography. The antibodies will be administered subcutaneously in combination with Poly (I:C) adjuvant in C57BL/6 mice. The anti-RBD humoral immune response induced will be evaluated and monitored by the determination of total IgG and IgG subclasses by ELISA and the neutralizing capacity will be evaluated in vitro by PRNT and VTN assays. RBD-specific cell responses will also be measured using assays such as ICS (Intracellular Cytokine Staining) and ELISPOT (Enzyme-linked Immunosorbent Spot). The protective capacity will be evaluated through the infection of transgenic mice for expression of the human ACE-2 receptor. We expect to contribute for the development of an innovative vaccine strategy that can significantly contribute to the control of the SARS-CoV-2 pandemic as well as for future infections with pandemic potential.