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

IntroductionIn 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 (EZIKV) is responsible for virus entry into host cells, is...

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Main Authors: Victória Alves Santos Lunardelli, Bianca da Silva Almeida, Juliana de Souza Apostolico, Thais Rezende, Marcio Massao Yamamoto, Samuel Santos Pereira, Maria Fernanda Campagnari Bueno, Lennon Ramos Pereira, Karina Inacio Carvalho, Renata Dezengrini Slhessarenko, Luis Carlos de Souza Ferreira, Silvia Beatriz Boscardin, Daniela Santoro Rosa
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1071041/full
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author Victória Alves Santos Lunardelli
Bianca da Silva Almeida
Juliana de Souza Apostolico
Thais Rezende
Marcio Massao Yamamoto
Samuel Santos Pereira
Maria Fernanda Campagnari Bueno
Lennon Ramos Pereira
Karina Inacio Carvalho
Karina Inacio Carvalho
Renata Dezengrini Slhessarenko
Luis Carlos de Souza Ferreira
Luis Carlos de Souza Ferreira
Silvia Beatriz Boscardin
Silvia Beatriz Boscardin
Daniela Santoro Rosa
Daniela Santoro Rosa
author_facet Victória Alves Santos Lunardelli
Bianca da Silva Almeida
Juliana de Souza Apostolico
Thais Rezende
Marcio Massao Yamamoto
Samuel Santos Pereira
Maria Fernanda Campagnari Bueno
Lennon Ramos Pereira
Karina Inacio Carvalho
Karina Inacio Carvalho
Renata Dezengrini Slhessarenko
Luis Carlos de Souza Ferreira
Luis Carlos de Souza Ferreira
Silvia Beatriz Boscardin
Silvia Beatriz Boscardin
Daniela Santoro Rosa
Daniela Santoro Rosa
author_sort Victória Alves Santos Lunardelli
collection DOAJ
description IntroductionIn 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 (EZIKV) 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 EZIKV 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.MethodsIn 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.ResultsTesting 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.ConclusionIn 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 doaj.art-521b2f86681b4cbb8137b632607af9292023-03-16T05:34:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.10710411071041Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cellsVictória Alves Santos Lunardelli0Bianca da Silva Almeida1Juliana de Souza Apostolico2Thais Rezende3Marcio Massao Yamamoto4Samuel Santos Pereira5Maria Fernanda Campagnari Bueno6Lennon Ramos Pereira7Karina Inacio Carvalho8Karina Inacio Carvalho9Renata Dezengrini Slhessarenko10Luis Carlos de Souza Ferreira11Luis Carlos de Souza Ferreira12Silvia Beatriz Boscardin13Silvia Beatriz Boscardin14Daniela Santoro Rosa15Daniela Santoro Rosa16Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo- Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, BrazilDepartmento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, BrazilDepartmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo- Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, BrazilDepartmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo- Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, BrazilDepartmento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, BrazilDepartmento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, BrazilDepartmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo- Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, BrazilDepartmento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, BrazilHospital Israelita Albert Einstein, São Paulo, BrazilCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, United StatesLaboratório de Virologia, Universidade Federal do Mato Grosso, Cuiabá, BrazilDepartmento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, BrazilPlataforma Científica Pasteur- Universidade de São Paulo, São Paulo, BrazilDepartmento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, BrazilInstituto Nacional de Ciência e Tecnologia (INCT) de Investigação em Imunologia (iii), São Paulo, BrazilDepartmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo- Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, BrazilInstituto Nacional de Ciência e Tecnologia (INCT) de Investigação em Imunologia (iii), São Paulo, BrazilIntroductionIn 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 (EZIKV) 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 EZIKV 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.MethodsIn 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.ResultsTesting 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.ConclusionIn conclusion, the present study highlights the differences in antigenicity and immunogenicity of recombinant ZIKV antigens produced in two heterologous protein expression systems.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1071041/fullsubunit vaccinesZika virusenvelope protein (E)recombinant proteinenvelope domain
spellingShingle Victória Alves Santos Lunardelli
Bianca da Silva Almeida
Juliana de Souza Apostolico
Thais Rezende
Marcio Massao Yamamoto
Samuel Santos Pereira
Maria Fernanda Campagnari Bueno
Lennon Ramos Pereira
Karina Inacio Carvalho
Karina Inacio Carvalho
Renata Dezengrini Slhessarenko
Luis Carlos de Souza Ferreira
Luis Carlos de Souza Ferreira
Silvia Beatriz Boscardin
Silvia Beatriz Boscardin
Daniela Santoro Rosa
Daniela Santoro Rosa
Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells
Frontiers in Immunology
subunit vaccines
Zika virus
envelope protein (E)
recombinant protein
envelope domain
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 subunit vaccines
Zika virus
envelope protein (E)
recombinant protein
envelope domain
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1071041/full
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