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
Abstract
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.
Funder
Fundação de Amparo à Pesquisa do Estado de São Paulo
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Cited by
2 articles.
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