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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Frontiers Media S.A.
2023-03-01
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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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