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Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells

INTRODUCTION: In the present study we evaluated the features of different recombinant forms of Zika virus (ZIKV) proteins produced in either bacterial (Eschericha coli) or insect cells (Drosophila melanogaster). The ZIKV-envelope glycoprotein (E(ZIKV)) is responsible for virus entry into host cells,...

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Autores principales: Lunardelli, Victória Alves Santos, Almeida, Bianca da Silva, Apostolico, Juliana de Souza, Rezende, Thais, Yamamoto, Marcio Massao, Pereira, Samuel Santos, Bueno, Maria Fernanda Campagnari, Pereira, Lennon Ramos, Carvalho, Karina Inacio, Slhessarenko, Renata Dezengrini, de Souza Ferreira, Luis Carlos, Boscardin, Silvia Beatriz, Rosa, Daniela Santoro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060818/
https://www.ncbi.nlm.nih.gov/pubmed/37006270
http://dx.doi.org/10.3389/fimmu.2023.1071041
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author Lunardelli, Victória Alves Santos
Almeida, Bianca da Silva
Apostolico, Juliana de Souza
Rezende, Thais
Yamamoto, Marcio Massao
Pereira, Samuel Santos
Bueno, Maria Fernanda Campagnari
Pereira, Lennon Ramos
Carvalho, Karina Inacio
Slhessarenko, Renata Dezengrini
de Souza Ferreira, Luis Carlos
Boscardin, Silvia Beatriz
Rosa, Daniela Santoro
author_facet Lunardelli, Victória Alves Santos
Almeida, Bianca da Silva
Apostolico, Juliana de Souza
Rezende, Thais
Yamamoto, Marcio Massao
Pereira, Samuel Santos
Bueno, Maria Fernanda Campagnari
Pereira, Lennon Ramos
Carvalho, Karina Inacio
Slhessarenko, Renata Dezengrini
de Souza Ferreira, Luis Carlos
Boscardin, Silvia Beatriz
Rosa, Daniela Santoro
author_sort Lunardelli, Victória Alves Santos
collection PubMed
description INTRODUCTION: In the present study we evaluated the features of different recombinant forms of Zika virus (ZIKV) proteins produced in either bacterial (Eschericha coli) or insect cells (Drosophila melanogaster). The ZIKV-envelope glycoprotein (E(ZIKV)) is responsible for virus entry into host cells, is the main target of neutralizing antibodies and has been used as a target antigen either for serological tests or for the development of subunit vaccines. The E(ZIKV) is composed of three structural and functional domains (EDI, EDII, and EDIII), which share extensive sequence conservation with the corresponding counterparts expressed by other flaviviruses, particularly the different dengue virus (DENV) subtypes. METHODS: In this study, we carried out a systematic comparison of the antigenicity and immunogenicity of recombinant EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells. For the antigenicity analysis we collected 88 serum samples from ZIKV-infected participants and 57 serum samples from DENV-infected. For immunogenicity, C57BL/6 mice were immunized with two doses of EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells to evaluate humoral and cellular immune response. In addition, AG129 mice were immunized with EZIKV and then challenge with ZIKV. RESULTS: Testing of samples collected from ZIKV-infected and DENV-infected participants demonstrated that the EZIKV and EDIIIZIKV produced in BL21 cells presented better sensitivity and specificity compared to proteins produced in S2 cells. In vivo analyses were carried out with C57BL/6 mice and the results indicated that, despite similar immunogenicity, antigens produced in S2 cells, particularly EZIKV and EDIIIZIKV, induced higher ZIKV-neutralizing antibody levels in vaccinated mice. In addition, immunization with EZIKV expressed in S2 cells delayed the onset of symptoms and increased survival rates in immunocompromised mice. All recombinant antigens, either produced in bacteria or insect cells, induced antigen-specific CD4+ and CD8+ T cell responses. CONCLUSION: In conclusion, the present study highlights the differences in antigenicity and immunogenicity of recombinant ZIKV antigens produced in two heterologous protein expression systems.
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spelling pubmed-100608182023-03-31 Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells Lunardelli, Victória Alves Santos Almeida, Bianca da Silva Apostolico, Juliana de Souza Rezende, Thais Yamamoto, Marcio Massao Pereira, Samuel Santos Bueno, Maria Fernanda Campagnari Pereira, Lennon Ramos Carvalho, Karina Inacio Slhessarenko, Renata Dezengrini de Souza Ferreira, Luis Carlos Boscardin, Silvia Beatriz Rosa, Daniela Santoro Front Immunol Immunology INTRODUCTION: In the present study we evaluated the features of different recombinant forms of Zika virus (ZIKV) proteins produced in either bacterial (Eschericha coli) or insect cells (Drosophila melanogaster). The ZIKV-envelope glycoprotein (E(ZIKV)) is responsible for virus entry into host cells, is the main target of neutralizing antibodies and has been used as a target antigen either for serological tests or for the development of subunit vaccines. The E(ZIKV) is composed of three structural and functional domains (EDI, EDII, and EDIII), which share extensive sequence conservation with the corresponding counterparts expressed by other flaviviruses, particularly the different dengue virus (DENV) subtypes. METHODS: In this study, we carried out a systematic comparison of the antigenicity and immunogenicity of recombinant EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells. For the antigenicity analysis we collected 88 serum samples from ZIKV-infected participants and 57 serum samples from DENV-infected. For immunogenicity, C57BL/6 mice were immunized with two doses of EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells to evaluate humoral and cellular immune response. In addition, AG129 mice were immunized with EZIKV and then challenge with ZIKV. RESULTS: Testing of samples collected from ZIKV-infected and DENV-infected participants demonstrated that the EZIKV and EDIIIZIKV produced in BL21 cells presented better sensitivity and specificity compared to proteins produced in S2 cells. In vivo analyses were carried out with C57BL/6 mice and the results indicated that, despite similar immunogenicity, antigens produced in S2 cells, particularly EZIKV and EDIIIZIKV, induced higher ZIKV-neutralizing antibody levels in vaccinated mice. In addition, immunization with EZIKV expressed in S2 cells delayed the onset of symptoms and increased survival rates in immunocompromised mice. All recombinant antigens, either produced in bacteria or insect cells, induced antigen-specific CD4+ and CD8+ T cell responses. CONCLUSION: In conclusion, the present study highlights the differences in antigenicity and immunogenicity of recombinant ZIKV antigens produced in two heterologous protein expression systems. Frontiers Media S.A. 2023-03-16 /pmc/articles/PMC10060818/ /pubmed/37006270 http://dx.doi.org/10.3389/fimmu.2023.1071041 Text en Copyright © 2023 Lunardelli, Almeida, Apostolico, Rezende, Yamamoto, Pereira, Bueno, Pereira, Carvalho, Slhessarenko, de Souza Ferreira, Boscardin and Rosa https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lunardelli, Victória Alves Santos
Almeida, Bianca da Silva
Apostolico, Juliana de Souza
Rezende, Thais
Yamamoto, Marcio Massao
Pereira, Samuel Santos
Bueno, Maria Fernanda Campagnari
Pereira, Lennon Ramos
Carvalho, Karina Inacio
Slhessarenko, Renata Dezengrini
de Souza Ferreira, Luis Carlos
Boscardin, Silvia Beatriz
Rosa, Daniela Santoro
Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells
title Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells
title_full Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells
title_fullStr Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells
title_full_unstemmed Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells
title_short Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells
title_sort diagnostic and vaccine potential of zika virus envelope protein (e) derivates produced in bacterial and insect cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060818/
https://www.ncbi.nlm.nih.gov/pubmed/37006270
http://dx.doi.org/10.3389/fimmu.2023.1071041
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