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

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2020
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Frontiers in Medical Technology
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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.

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PEREIRA, LENNON R.; ALVES, RUBENS P. dos S.; SALES, NATIELY S.; ANDREATA-SANTOS, ROBERT; VENCESLAU-CARVALHO, ALEXIA A.; PEREIRA, SAMUEL S.; CASTRO-AMARANTE, MARIA F.; RODRIGUES-JESUS, MONICA J.; FAVARO, MARIANNA T. de P.; CHURA-CHAMBI, ROSA M.; MORGANTI, LIGIA; FERREIRA, LUIS C. de S. 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. Frontiers in Medical Technology, v. 2, p. 1-14, 2020. DOI: 10.3389/fmedt.2020.604160. Disponível em: http://200.136.52.105/handle/123456789/31770. Acesso em: 29 Mar 2024.
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