RBD and Spike DNA-Based Immunization in Rabbits Elicited IgG Avidity Maturation and High Neutralizing Antibody Responses against SARS-CoV-2

Hernan H M da Costa; Diego J B Orts; Andrew D Moura; Amaro N Duarte-Neto; Cinthya S Cirqueira; Rodrigo A Réssio; Cristina T Kanamura; Karen Miguita; Jerenice E Ferreira; Raimunda T M Santos; Patricia P Adriani; Jair P Cunha-Junior; Renato M Astray; Regina M Catarino; Marcelo Lancelotti; Carlos R Prudencio

doi:10.3390/v15020555

RBD and Spike DNA-Based Immunization in Rabbits Elicited IgG Avidity Maturation and High Neutralizing Antibody Responses against SARS-CoV-2

Viruses. 2023 Feb 17;15(2):555. doi: 10.3390/v15020555.

Authors

Hernan H M da Costa^{1

2}, Diego J B Orts¹, Andrew D Moura¹, Amaro N Duarte-Neto³, Cinthya S Cirqueira³, Rodrigo A Réssio³, Cristina T Kanamura³, Karen Miguita³, Jerenice E Ferreira³, Raimunda T M Santos³, Patricia P Adriani^{4

5}, Jair P Cunha-Junior⁶, Renato M Astray⁷, Regina M Catarino³, Marcelo Lancelotti⁸, Carlos R Prudencio^{1

2}

Affiliations

¹ Immunology Center, Institute Adolfo Lutz, São Paulo 01246-902, Brazil.
² Graduate Program Interunits in Biotechnology, University of São Paulo, São Paulo 05508-000, Brazil.
³ Pathology Center, Institute Adolfo Lutz, São Paulo 01246-902, Brazil.
⁴ Skinzymes Biotechnology Ltd., São Paulo 05441-040, Brazil.
⁵ Laboratory of Nanopharmaceuticals and Delivery Systems, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.
⁶ Laboratory of Immunochemistry and Immunotechnology, Department of Immunology, Federal University of Uberlândia, Uberlândia 38405-317, Brazil.
⁷ Multi-Purpose Laboratory, Butantan Institute, São Paulo 05503-900, Brazil.
⁸ Faculty of Pharmaceutical Sciences, Campinas State University, Campinas 13083-871, Brazil.

Abstract

Neutralizing antibodies (nAbs) are a critical part of coronavirus disease 2019 (COVID-19) research as they are used to gain insight into the immune response to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infections. Among the technologies available for generating nAbs, DNA-based immunization methods are an alternative to conventional protocols. In this pilot study, we investigated whether DNA-based immunization by needle injection in rabbits was a viable approach to produce a functional antibody response. We demonstrated that three doses of DNA plasmid carrying the gene encoding the full-length spike protein (S) or the receptor binding domain (RBD) of SARS-CoV-2 induced a time-dependent increase in IgG antibody avidity maturation. Moreover, the IgG antibodies displayed high cross neutralization by live SARS-CoV-2 and pseudoviruses neutralization assays. Thus, we established a simple, low cost and feasible DNA-based immunization protocol in rabbits that elicited high IgG avidity maturation and nAbs production against SARS-CoV-2, highlighting the importance of DNA-based platforms for developing new immunization strategies against SARS-CoV-2 and future emerging epidemics.

Keywords: COVID-19; DNA immunization; SARS-CoV-2; antibody response; avidity; soroneutralization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing
COVID-19* / prevention & control
Immunization
Immunoglobulin G
Pilot Projects
Rabbits
SARS-CoV-2* / genetics

Substances

Antibodies, Neutralizing
Immunoglobulin G

Grants and funding

This work was supported by grants from the National Council for Scientific and Technological Development (CNPq Grant ID 130843/2020-2 to HHMC and 440812/2016-0 to CRP), Ministry of Health, Special Health Fund for Mass Immunization and Disease Control of the State Department of Health of the State of São Paulo (FESIMA), Coordination for the Improvement of Higher Education Personnel (CAPES Grant ID 88887.703323/2022-00 to HHMC, 88881.130804/2016–01 to CRP and 88887.506965/2020–0 to ML) and the São Paulo Research Foundation (FAPESP Grant ID 17/50333-7 to CRP).