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

Autor: Lunardelli VAS; Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo- Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil., Almeida BDS; Departmento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, Brazil., Apostolico JS; Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo- Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil., Rezende T; Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo- Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil., Yamamoto MM; Departmento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, Brazil., Pereira SS; Departmento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, Brazil., Bueno MFC; Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo- Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil., Pereira LR; Departmento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, Brazil., Carvalho KI; Hospital Israelita Albert Einstein, São Paulo, Brazil.; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, United States., Slhessarenko RD; Laboratório de Virologia, Universidade Federal do Mato Grosso, Cuiabá, Brazil., de Souza Ferreira LC; Departmento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, Brazil.; Plataforma Científica Pasteur- Universidade de São Paulo, São Paulo, Brazil., Boscardin SB; Departmento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, Brazil.; Instituto Nacional de Ciência e Tecnologia (INCT) de Investigação em Imunologia (iii), São Paulo, Brazil., Rosa DS; Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo- Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil.; Instituto Nacional de Ciência e Tecnologia (INCT) de Investigação em Imunologia (iii), São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2023 Mar 16; Vol. 14, pp. 1071041. Date of Electronic Publication: 2023 Mar 16 (Print Publication: 2023).
DOI: 10.3389/fimmu.2023.1071041
Abstrakt: 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Lunardelli, Almeida, Apostolico, Rezende, Yamamoto, Pereira, Bueno, Pereira, Carvalho, Slhessarenko, de Souza Ferreira, Boscardin and Rosa.)
Databáze: MEDLINE
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