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
| Autor: | Luís Carlos de Souza Ferreira, Samuel Santos Pereira, Natiely Silva Sales, Marianna Teixeira de Pinho Favaro, Ligia Morganti, Mônica Josiane Rodrigues-Jesus, Aléxia Adrianne Venceslau-Carvalho, Lennon Ramos Pereira, Robert Andreata-Santos, Rosa Maria Chura-Chambi, Rúbens Prince dos Santos Alves, Maria Fernanda de Castro-Amarante |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
DNA vaccine Medical Technology medicine.medical_treatment viruses Viremia medicine.disease_cause NS1 protein Zika virus DNA vaccination 03 medical and health sciences 0302 clinical medicine Immune system flavivirus medicine gD protein DNA RECOMBINANTE Original Research biology biochemical phenomena metabolism and nutrition medicine.disease biology.organism_classification Virology HSV-1 Flavivirus 030104 developmental biology Herpes simplex virus 030220 oncology & carcinogenesis biology.protein Antibody Adjuvant |
| Zdroj: | Frontiers in Medical Technology Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 2673-3129 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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