Artigo de peri??dico
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
Registro en:
2673-3129
2
10.3389/fmedt.2020.604160
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Autor
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.
Resumen
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-Barr?? 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. Funda????o de Amparo ?? Pesquisa do Estado de S??o Paulo (FAPESP) Coordena????o de Aperfei??oamento de Pessoal de N??vel Superior (CAPES) FAPESP: 16/20045-7; 16/05570-8; 14/17595-0; 16/14344-1; 16/23560-0; 17/09661-0; 18/14459-9; 18/08199-4 CAPES: 88887.473724/2020-00; 88887.185337/2018-00
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