Enhanced Immunogenicity and Protective Effects against SARS-CoV-2 Following Immunization with a Recombinant RBD-IgG Chimeric Protein
Mariângela de Oliveira Silva,
Maria Fernanda Castro-Amarante,
Alexia Adrianne Venceslau-Carvalho,
Bianca da Silva Almeida,
Isabela Pazotti Daher,
Guilherme Antonio de Souza-Silva,
Marcio Massao Yamamoto,
Gabriela Koike,
Edmarcia Elisa de Souza,
Carsten Wrenger,
Luís Carlos de Souza Ferreira,
Silvia Beatriz Boscardin
Affiliations
Mariângela de Oliveira Silva
Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Maria Fernanda Castro-Amarante
Laboratory of Vaccine Development, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Alexia Adrianne Venceslau-Carvalho
Laboratory of Vaccine Development, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Bianca da Silva Almeida
Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Isabela Pazotti Daher
Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo 05403-000, Brazil
Guilherme Antonio de Souza-Silva
Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Marcio Massao Yamamoto
Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Gabriela Koike
Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Edmarcia Elisa de Souza
Unit for Drug Discovery, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Carsten Wrenger
Unit for Drug Discovery, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Luís Carlos de Souza Ferreira
Laboratory of Vaccine Development, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Silvia Beatriz Boscardin
Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
The unprecedented global impact caused by SARS-CoV-2 imposed huge health and economic challenges, highlighting the urgent need for safe and effective vaccines. The receptor-binding domain (RBD) of SARS-CoV-2 is the major target for neutralizing antibodies and for vaccine formulations. Nonetheless, the low immunogenicity of the RBD requires the use of alternative strategies to enhance its immunological properties. Here, we evaluated the use of a subunit vaccine antigen generated after the genetic fusing of the RBD with a mouse IgG antibody. Subcutaneous administration of RBD-IgG led to the extended presence of the protein in the blood of immunized animals and enhanced RBD-specific IgG titers. Furthermore, RBD-IgG immunized mice elicited increased virus neutralizing antibody titers, measured both with pseudoviruses and with live original (Wuhan) SARS-CoV-2. Immunized K18-hACE2 mice were fully resistant to the lethal challenge of the Wuhan SARS-CoV-2, demonstrated by the control of body-weight loss and virus loads in their lungs and brains. Thus, we conclude that the genetic fusion of the RBD with an IgG molecule enhanced the immunogenicity of the antigen and the generation of virus-neutralizing antibodies, supporting the use of IgG chimeric antigens as an approach to improve the performance of SARS-CoV-2 subunit vaccines.
