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ZEBRAFISH STUDIES ON THE VACCINE CANDIDATE TO COVID-19, THE SPIKE PROTEIN: PRODUCTION OF ANTIBODY AND ADVERSE REACTION
Fernandes, Bianca H. Ventura et al. | Date Issued: 2020
Author
Fernandes, Bianca H. Ventura
Feitosa, Natália Martins
Barbosa, Ana Paula
Bomfim, Camila Gasque
Garnique, Anali M. B.
Gomes, Francisco I. F.
Nakajima, Rafael T.
Belo, Marco A. A.
Eto, Silas Fernandes
Fernandes, Dayanne Carla
Malafaia, Guilherme
Manrique, Wilson G.
Conde, Gabriel
Rosales, Roberta R. C.
Todeschini, Iris
Rivero, Ilo
Llontop, Edgar
G. Sgro, German
Oka, Gabriel Umaji
Bueno, Natalia F.
Ferraris, Fausto K.
Magalhaes, Mariana T. Q. de
Medeiros, Renata J.
Gomes, Juliana M. M.
Junqueira, Mara de Souza
Conceição, Katia
Pontes, Letícia G.
Condino-Neto, Antonio
Perez, Andrea C.
Barcellos, Leonardo J. G.
Correa Junior, Jose Dias
Dorlass, Erick G.
Camara, Niels O. S.
Durigon, Edison Luiz
Cunha, Fernando Q.
Nóbrega, Rafael H.
Machado-Santelli, Glaucia M.
Farah, Chuck
Veras, Flávio P.
Galindo-Villegas, Jorge
Costa-Lotufo, Leticia
Cunha, Thiago M.
Chammas, Roger
Guzzo, Cristiane R.
Carvalho, Luciani R.
Charlie-Silva, Ives
Affilliation
Universidade de São Paulo. Faculdade de Medicina. Laboratório de Controle Genético e Sanitário. Diretoria Técnica de Apoio ao Ensino e Pesquisa. Departamento de Clinica medica e Laboratório de Hormônios e Genética Molecular. São Paulo, SP, Brazil.
Federal University of Rio de Janeiro. Institute of Biodiversity and Sustainability. Integrated Laboratory of Translational Bioscience. Macaé, RJ, Brazil.
University of São Paulo. Institute of Biomedical Sciences. Department of Microbiology. São Paulo, SP, Brazil.
University of São Paulo. Institute of Biomedical Sciences. Department of Microbiology. São Paulo, SP, Brazil.
University of São Paulo. Institute of Biomedical Sciences. Department of Cell Biology. São Paulo, SP, Brazil.
University of São Paulo, Ribeirão Preto. Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School. São Paulo, SP, Brazil / University of São Paulo. Department of Pharmacology, Ribeirão Preto Medical School. Ribeirão Preto, SP, Brazil.
São Paulo State University. Institute of Biosciences. Department of Morphology. Reproductive and Molecular Biology Group. Botucatu, SP, Brazil.
São Paulo State University. Department of Preventive Veterinary Medicine. Jaboticabal, SP, Brazil / Brasil University. Laboratory of Animal Pharmacology and Toxicology. São Paulo, SP, Brazil.
Federal University of Roraima. Postgraduate Program in Health Sciences. Roraima, RR, Brazil.
Butantan Institute. Immunochemistry Laboratory. São Paulo, SP, Brazil.
Goiano Federal Institute. Urutaí Campus. Biological Research Laboratory. Goiânia, GO, Brazil.
Federal University of Rondônia. Rolim de Moura Campus. Aquaculture Health Research and Extension Group. Aquaculture Health Laboratory. Department of Veterinary Medicine. Rondônia, RO, Brazil.
São Paulo State University. Department of Preventive Veterinary Medicine.Jaboticabal. São Paulo, SP, Brazil.
University of São Paulo, Ribeirão Preto. Department of Cell and Molecular Biology. Ribeirão Preto Medical School. Ribeirão Preto, SP, Brazil.
Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brazil.
Pontificia Universidade Catolica de Minas Gerais. Belo Horizonte, MG, Brazil.
Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brazil.
Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brazil.
Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brazil.
Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brazil.
Oswaldo Cruz Foundation. The National Institute for Health Quality Control. Department of Pharmacology and Toxicology. Rio de Janeiro, RJ, Brazil.
Federal University of Minas Gerais. Institute of Biological Sciences. Department of Biochemistry and Immunology. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Laboratório de Fisiologia. Rio de Janeiro, RJ, Brasil.
Universidade de São Paulo. Institute of Biomedical Sciences. Transplantation Immunobiology Lab, Department of Immunology. São Paulo, SP, Brazil.
University of São Paulo. Faculty of Medicine. Institute of the State of São Paulo. Center for Translational Research in Oncology, Cancer. São Paulo, SP, Brazil.
Federal University of São Paulo. Laboratory of Peptide Biochemistry, São Paulo, SP, Brazil.
University São Paulo. Institute Biomedical Sciences. Laboratory of Human Immunology. Department Immunology. São Paulo, SP, Brazil.
University São Paulo. Institute Biomedical Sciences. Laboratory of Human Immunology. Department Immunology. São Paulo, SP, Brazil.
Universidade Federal de Minas Gerais. Department of Pharmacology. Belo Horizonte, MG, Brazil.
Federal University of Santa Maria. Graduate Program of Pharmacology. Brasília, DF, Brazil / University of Passo Fundo. Laboratory of Fish Physiology. Graduate Program of Bioexperimentation and of Environmental Sciences. Passo Fundo, RS, Brazil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia Laboratório do Estudo da Interação Químico Biológica e da Reprodução Animal. Belo Horizonte, MG, Brazil.
University of São Paulo. Institute of Biomedical Sciences. Department of Microbiology. São Paulo, SP, Brazil.
University of São Paulo. Institute of Biomedical Sciences. Transplantation Immunobiology Laboratory. Department of Immunology. São Paulo, SP, Brazil.
University of São Paulo. Institute of Biomedical Sciences. Department of Microbiology. São Paulo, SP, Brazil.
University of São Paulo, Ribeirão Preto. Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School. São Paulo, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Pharmacology. Ribeirão Preto, SP, Brazil.
São Paulo State University. Institute of Biosciences. Reproductive and Molecular Biology Group. Department of Morphology. Botucatu, SP, Brazil.
University of São Paulo. Institute of Biomedical Sciences. Department of Cell Biology. São Paulo, SP, Brazil.
Universidade de São Paulo. Departamento de Bioquímica, Instituto de Química. São Paulo, SP, Brazil.
University of São Paulo. Ribeirão Preto Medical School. Center of Research in Inflammatory Diseases. Ribeirão Preto, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Pharmacology. Ribeirão Preto, SP, Brazil.
Nord University. Faculty of Biosciences and Aquaculture. Bodø, Norway.
University of São Paulo. Institute of Biomedical Sciences. Department of Pharmacology. São Paulo, SP, Brazil.
University of São Paulo. Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School. Ribeirão Preto, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Pharmacology. Ribeirão Preto, SP, Brazil.
Universidade de São Paulo. Faculdade de Medicina. Diretoria Técnica de Apoio ao Ensino e Pesquisa. Laboratório de Controle Genético e Sanitário. São Paulo, SP, Brazil / Universidade de São Paulo. Faculdade de Medicina. Instituto do Câncer do Estado de São Paulo. Centro de Investigação Translacional em Oncologia. São Paulo, SP, Brazil.
University of São Paulo. Institute of Biomedical Sciences. Department of Microbiology. São Paulo, SP, Brazil.
Universidade de São Paulo. Faculdade de Medicina. Diretoria Técnica de Apoio ao Ensino e Pesquisa. Laboratório de Controle Genético e Sanitário. Disciplina de endocrinologia do departamento de Clinica medica e Laboratório de Hormônios e Genética Molecular, LIM 42. São Paulo, SP, Brazil.
Universidade de São Paulo. Institute of Biomedical Sciences. Department of Pharmacology. São Paulo, SP, Brazil.
Abstract
Establishing new experimental animal models to assess the safety and immune response to the antigen used in the development of COVID-19 vaccine is an imperative issue. Based on the advantages of using zebrafish as a model in research, herein we suggest doing this to test the safety of the putative vaccine candidates and to study immune response against the virus. We produced a recombinant N-terminal fraction of the Spike SARS-CoV-2 protein and injected it into adult female zebrafish. The specimens generated humoral immunity and passed the antibodies to the eggs. However, they presented adverse reactions and inflammatory responses similar to severe cases of human COVID-19. The analysis of the structure and function of zebrafish and human Angiotensin-converting enzyme 2, the main human receptor for virus infection, presented remarkable sequence similarities. Moreover, bioinformatic analysis predicted protein-protein interaction of the Spike SARS-CoV-2 fragment and the Toll-like receptor pathway. It might help in the choice of future therapeutic pharmaceutical drugs to be studied. Based on the in vivo and in silico results presented here, we propose the zebrafish as a model for translational research into the safety of the vaccine and the immune response of the vertebrate organism to the SARS-CoV-2 virus.
Keywords in Portuguese
COVID-19
SARS-CoV-2
 
Keywords
Zebrafish
Immune Response
Vaccine
Antibody
Adverse Reaction
COVID-19
 
Citation
FERNANDES Bianca H. et al. Ventura etal. Zebrafish studies on the vaccine candidate to COVID-19, the Spike protein: Production of antibody and adverse reaction. bioRxiv preprint, p. 1-47, 2020. Inclui Material Suplementar.
DOI
10.1101/2020.10.20.346262