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BIBTEX RIS

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

2020; Frontiers Media; Volume: 2; Linguagem: Inglês

10.3389/fmedt.2020.604160

ISSN

2673-3129

Autores

Lennon Ramos Pereira, Rúbens Prince dos Santos Alves, Natiely Silva Sales, Robert Andreata‐Santos, Aléxia Adrianne Venceslau-Carvalho, Samuel Santos Pereira, Maria Fernanda de Castro‐Amarante, Mônica Josiane Rodrigues‐Jesus, Marianna Teixeira de Pinho Favaro, Rosa Maria Chura‐Chambi, Lígia Morganti, Luís Carlos de Souza Ferreira,

Tópico(s)

Malaria Research and Control

Resumo

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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