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Enhanced Immune Responses and Protective Immunity to Zika Virus Induced by a DNA Vaccine Encoding a Chimeric NS1 Fused With Type 1 Herpes Virus gD Protein
Zika virus (ZIKV) is a globally-distributed flavivirus transmitted to humans by Aedes mosquitoes, usually causing mild symptoms that may evolve to severe conditions, including neurological alterations, such as neonatal microcephaly and Guillain-Barré syndrome. Due to the absence of specific and effe...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757838/ https://www.ncbi.nlm.nih.gov/pubmed/35047887 http://dx.doi.org/10.3389/fmedt.2020.604160 |
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author | Pereira, Lennon Ramos Alves, Rúbens Prince dos Santos Sales, Natiely Silva Andreata-Santos, Robert Venceslau-Carvalho, Aléxia Adrianne Pereira, Samuel Santos Castro-Amarante, Maria Fernanda Rodrigues-Jesus, Mônica Josiane Favaro, Marianna Teixeira de Pinho Chura-Chambi, Rosa Maria Morganti, Ligia Ferreira, Luís Carlos de Souza |
author_facet | Pereira, Lennon Ramos Alves, Rúbens Prince dos Santos Sales, Natiely Silva Andreata-Santos, Robert Venceslau-Carvalho, Aléxia Adrianne Pereira, Samuel Santos Castro-Amarante, Maria Fernanda Rodrigues-Jesus, Mônica Josiane Favaro, Marianna Teixeira de Pinho Chura-Chambi, Rosa Maria Morganti, Ligia Ferreira, Luís Carlos de Souza |
author_sort | Pereira, Lennon Ramos |
collection | PubMed |
description | Zika virus (ZIKV) is a globally-distributed flavivirus transmitted to humans by Aedes mosquitoes, usually causing mild symptoms that may evolve to severe conditions, including neurological alterations, such as neonatal microcephaly and Guillain-Barré syndrome. Due to the absence of specific and effective preventive methods, we designed a new subunit vaccine based on a DNA vector (pgDNS1-ZIKV) encoding the non-structural protein 1 (NS1) genetically fused to the Herpes Simplex Virus (HSV) glycoprotein D (gD) protein. Recombinant plasmids were replicated in Escherichia coli and the expression of the target protein was confirmed in transfected HEK293 cells. C57BL/6 and AB6 (IFNAR1–/–) mice were i.m. immunized by electroporation in order to evaluate pgDNS1-ZIKV immunogenicity. After two doses, high NS1-specific IgG antibody titers were measured in serum samples collected from pgDNS1-ZIKV-immunized mice. The NS1-specific antibodies were capable to bind the native protein expressed in infected mammalian cells. Immunization with pgDNS1-ZIKV increased both humoral and cellular immune responses regarding mice immunized with a ZIKV NS1 encoding vaccine. Immunization with pgDNS1-ZIKV reduced viremia and morbidity scores leading to enhanced survival of immunodeficient AB6 mice challenged with a lethal virus load. These results give support to the use of ZIKV NS1 as a target antigen and further demonstrate the relevant adjuvant effects of HSV-1 gD. |
format | Online Article Text |
id | pubmed-8757838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87578382022-01-18 Enhanced Immune Responses and Protective Immunity to Zika Virus Induced by a DNA Vaccine Encoding a Chimeric NS1 Fused With Type 1 Herpes Virus gD Protein Pereira, Lennon Ramos Alves, Rúbens Prince dos Santos Sales, Natiely Silva Andreata-Santos, Robert Venceslau-Carvalho, Aléxia Adrianne Pereira, Samuel Santos Castro-Amarante, Maria Fernanda Rodrigues-Jesus, Mônica Josiane Favaro, Marianna Teixeira de Pinho Chura-Chambi, Rosa Maria Morganti, Ligia Ferreira, Luís Carlos de Souza Front Med Technol Medical Technology Zika virus (ZIKV) is a globally-distributed flavivirus transmitted to humans by Aedes mosquitoes, usually causing mild symptoms that may evolve to severe conditions, including neurological alterations, such as neonatal microcephaly and Guillain-Barré syndrome. Due to the absence of specific and effective preventive methods, we designed a new subunit vaccine based on a DNA vector (pgDNS1-ZIKV) encoding the non-structural protein 1 (NS1) genetically fused to the Herpes Simplex Virus (HSV) glycoprotein D (gD) protein. Recombinant plasmids were replicated in Escherichia coli and the expression of the target protein was confirmed in transfected HEK293 cells. C57BL/6 and AB6 (IFNAR1–/–) mice were i.m. immunized by electroporation in order to evaluate pgDNS1-ZIKV immunogenicity. After two doses, high NS1-specific IgG antibody titers were measured in serum samples collected from pgDNS1-ZIKV-immunized mice. The NS1-specific antibodies were capable to bind the native protein expressed in infected mammalian cells. Immunization with pgDNS1-ZIKV increased both humoral and cellular immune responses regarding mice immunized with a ZIKV NS1 encoding vaccine. Immunization with pgDNS1-ZIKV reduced viremia and morbidity scores leading to enhanced survival of immunodeficient AB6 mice challenged with a lethal virus load. These results give support to the use of ZIKV NS1 as a target antigen and further demonstrate the relevant adjuvant effects of HSV-1 gD. Frontiers Media S.A. 2020-12-03 /pmc/articles/PMC8757838/ /pubmed/35047887 http://dx.doi.org/10.3389/fmedt.2020.604160 Text en Copyright © 2020 Pereira, Alves, Sales, Andreata-Santos, Venceslau-Carvalho, Pereira, Castro-Amarante, Rodrigues-Jesus, Favaro, Chura-Chambi, Morganti and Ferreira. 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 | Medical Technology Pereira, Lennon Ramos Alves, Rúbens Prince dos Santos Sales, Natiely Silva Andreata-Santos, Robert Venceslau-Carvalho, Aléxia Adrianne Pereira, Samuel Santos Castro-Amarante, Maria Fernanda Rodrigues-Jesus, Mônica Josiane Favaro, Marianna Teixeira de Pinho Chura-Chambi, Rosa Maria Morganti, Ligia Ferreira, Luís Carlos de Souza Enhanced Immune Responses and Protective Immunity to Zika Virus Induced by a DNA Vaccine Encoding a Chimeric NS1 Fused With Type 1 Herpes Virus gD Protein |
title | Enhanced Immune Responses and Protective Immunity to Zika Virus Induced by a DNA Vaccine Encoding a Chimeric NS1 Fused With Type 1 Herpes Virus gD Protein |
title_full | Enhanced Immune Responses and Protective Immunity to Zika Virus Induced by a DNA Vaccine Encoding a Chimeric NS1 Fused With Type 1 Herpes Virus gD Protein |
title_fullStr | Enhanced Immune Responses and Protective Immunity to Zika Virus Induced by a DNA Vaccine Encoding a Chimeric NS1 Fused With Type 1 Herpes Virus gD Protein |
title_full_unstemmed | Enhanced Immune Responses and Protective Immunity to Zika Virus Induced by a DNA Vaccine Encoding a Chimeric NS1 Fused With Type 1 Herpes Virus gD Protein |
title_short | Enhanced Immune Responses and Protective Immunity to Zika Virus Induced by a DNA Vaccine Encoding a Chimeric NS1 Fused With Type 1 Herpes Virus gD Protein |
title_sort | enhanced immune responses and protective immunity to zika virus induced by a dna vaccine encoding a chimeric ns1 fused with type 1 herpes virus gd protein |
topic | Medical Technology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757838/ https://www.ncbi.nlm.nih.gov/pubmed/35047887 http://dx.doi.org/10.3389/fmedt.2020.604160 |
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