Rational design and production of a chimeric antigen targeting Zika virus that induces neutralizing antibodies in mice
The Zika virus (ZIKV) is considered a public health problem worldwide due to its association with the development of microcephaly and the Guillain-Barré syndrome. Currently, there is no specific treatment or vaccine approved to combat this disease, and thus, developing safe and effective vaccines is...
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| Veröffentlicht in: | Vaccine 2024-06, Vol.42 (17), p.3674-3683 |
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| creator | Miranda-López, Arleth González-Ortega, Omar Govea-Alonso, Dania O. Betancourt-Mendiola, Lourdes Comas-García, Mauricio Rosales-Mendoza, Sergio |
| description | The Zika virus (ZIKV) is considered a public health problem worldwide due to its association with the development of microcephaly and the Guillain-Barré syndrome. Currently, there is no specific treatment or vaccine approved to combat this disease, and thus, developing safe and effective vaccines is a relevant goal. In this study, a multi-epitope protein called rpZDIII was designed based on a series of ZIKV antigenic sequences, a bacterial carrier, and linkers. The analysis of the predicted 3D structure of the rpZDIII chimeric antigen was performed on the AlphaFold 2 server, and it was produced in E. coli and purified from inclusion bodies, followed by solubilization and refolding processes. The yield achieved for rpZDIII was 11 mg/L in terms of pure soluble recombinant protein per liter of fermentation. rpZDIII was deemed immunogenic since it induced serum IgG and IgM responses in mice upon subcutaneous immunization in a three-dose scheme. Moreover, sera from mice immunized with rpZDIII showed neutralizing activity against ZIKV. Therefore, this study reveals rpZDIII as a promising immunogen for the development of a rationally designed multi-epitope vaccine against ZIKV, and completion of its preclinical evaluation is guaranteed. |
| doi_str_mv | 10.1016/j.vaccine.2024.04.080 |
| format | Article |
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Currently, there is no specific treatment or vaccine approved to combat this disease, and thus, developing safe and effective vaccines is a relevant goal. In this study, a multi-epitope protein called rpZDIII was designed based on a series of ZIKV antigenic sequences, a bacterial carrier, and linkers. The analysis of the predicted 3D structure of the rpZDIII chimeric antigen was performed on the AlphaFold 2 server, and it was produced in E. coli and purified from inclusion bodies, followed by solubilization and refolding processes. The yield achieved for rpZDIII was 11 mg/L in terms of pure soluble recombinant protein per liter of fermentation. rpZDIII was deemed immunogenic since it induced serum IgG and IgM responses in mice upon subcutaneous immunization in a three-dose scheme. Moreover, sera from mice immunized with rpZDIII showed neutralizing activity against ZIKV. Therefore, this study reveals rpZDIII as a promising immunogen for the development of a rationally designed multi-epitope vaccine against ZIKV, and completion of its preclinical evaluation is guaranteed.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2024.04.080</identifier><identifier>PMID: 38749821</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Amino acids ; Antibodies ; Antigens ; Biomass ; blood serum ; Chimeric antigen ; Dengue fever ; Design ; E coli ; Epidemics ; Epitopes ; Escherichia coli ; Fermentation ; Guillain-Barre syndrome ; Humoral response ; Immunization ; Immunogenicity ; Immunoglobulin G ; Immunoglobulin M ; Inclusion bodies ; Infections ; Microencephaly ; Multi-epitope vaccine ; Neutralizing ; Neutralizing antibodies ; Protein expression ; Proteins ; Public health ; R&D ; recombinant proteins ; Research & development ; Sequences ; Solubilization ; Vaccines ; Vector-borne diseases ; Zika fever disease ; Zika virus</subject><ispartof>Vaccine, 2024-06, Vol.42 (17), p.3674-3683</ispartof><rights>2024 Elsevier India Pvt Ltd.</rights><rights>Copyright © 2024 Elsevier India Pvt Ltd. Published by Elsevier Ltd. All rights reserved.</rights><rights>2024. Elsevier India Pvt Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c374t-11e8aa20fc00f18a56a579c0448788c15b216feb151dcf5a2ca768bc4ed91e593</cites><orcidid>0000-0002-5878-8078</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0264410X24005188$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38749821$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miranda-López, Arleth</creatorcontrib><creatorcontrib>González-Ortega, Omar</creatorcontrib><creatorcontrib>Govea-Alonso, Dania O.</creatorcontrib><creatorcontrib>Betancourt-Mendiola, Lourdes</creatorcontrib><creatorcontrib>Comas-García, Mauricio</creatorcontrib><creatorcontrib>Rosales-Mendoza, Sergio</creatorcontrib><title>Rational design and production of a chimeric antigen targeting Zika virus that induces neutralizing antibodies in mice</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>The Zika virus (ZIKV) is considered a public health problem worldwide due to its association with the development of microcephaly and the Guillain-Barré syndrome. Currently, there is no specific treatment or vaccine approved to combat this disease, and thus, developing safe and effective vaccines is a relevant goal. In this study, a multi-epitope protein called rpZDIII was designed based on a series of ZIKV antigenic sequences, a bacterial carrier, and linkers. The analysis of the predicted 3D structure of the rpZDIII chimeric antigen was performed on the AlphaFold 2 server, and it was produced in E. coli and purified from inclusion bodies, followed by solubilization and refolding processes. The yield achieved for rpZDIII was 11 mg/L in terms of pure soluble recombinant protein per liter of fermentation. rpZDIII was deemed immunogenic since it induced serum IgG and IgM responses in mice upon subcutaneous immunization in a three-dose scheme. Moreover, sera from mice immunized with rpZDIII showed neutralizing activity against ZIKV. Therefore, this study reveals rpZDIII as a promising immunogen for the development of a rationally designed multi-epitope vaccine against ZIKV, and completion of its preclinical evaluation is guaranteed.</description><subject>Amino acids</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Biomass</subject><subject>blood serum</subject><subject>Chimeric antigen</subject><subject>Dengue fever</subject><subject>Design</subject><subject>E coli</subject><subject>Epidemics</subject><subject>Epitopes</subject><subject>Escherichia coli</subject><subject>Fermentation</subject><subject>Guillain-Barre syndrome</subject><subject>Humoral response</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin M</subject><subject>Inclusion bodies</subject><subject>Infections</subject><subject>Microencephaly</subject><subject>Multi-epitope vaccine</subject><subject>Neutralizing</subject><subject>Neutralizing antibodies</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Public health</subject><subject>R&D</subject><subject>recombinant proteins</subject><subject>Research & development</subject><subject>Sequences</subject><subject>Solubilization</subject><subject>Vaccines</subject><subject>Vector-borne diseases</subject><subject>Zika fever disease</subject><subject>Zika 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Currently, there is no specific treatment or vaccine approved to combat this disease, and thus, developing safe and effective vaccines is a relevant goal. In this study, a multi-epitope protein called rpZDIII was designed based on a series of ZIKV antigenic sequences, a bacterial carrier, and linkers. The analysis of the predicted 3D structure of the rpZDIII chimeric antigen was performed on the AlphaFold 2 server, and it was produced in E. coli and purified from inclusion bodies, followed by solubilization and refolding processes. The yield achieved for rpZDIII was 11 mg/L in terms of pure soluble recombinant protein per liter of fermentation. rpZDIII was deemed immunogenic since it induced serum IgG and IgM responses in mice upon subcutaneous immunization in a three-dose scheme. Moreover, sera from mice immunized with rpZDIII showed neutralizing activity against ZIKV. Therefore, this study reveals rpZDIII as a promising immunogen for the development of a rationally designed multi-epitope vaccine against ZIKV, and completion of its preclinical evaluation is guaranteed.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>38749821</pmid><doi>10.1016/j.vaccine.2024.04.080</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5878-8078</orcidid></addata></record> |
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| subjects | Amino acids Antibodies Antigens Biomass blood serum Chimeric antigen Dengue fever Design E coli Epidemics Epitopes Escherichia coli Fermentation Guillain-Barre syndrome Humoral response Immunization Immunogenicity Immunoglobulin G Immunoglobulin M Inclusion bodies Infections Microencephaly Multi-epitope vaccine Neutralizing Neutralizing antibodies Protein expression Proteins Public health R&D recombinant proteins Research & development Sequences Solubilization Vaccines Vector-borne diseases Zika fever disease Zika virus |
| title | Rational design and production of a chimeric antigen targeting Zika virus that induces neutralizing antibodies in mice |
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