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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Pereira, Lennon Ramos ; dos Santos Alves, Rubens Prince ; Sales, Natiely Silva ; Andreata-Santos, Robert ; Venceslau-Carvalho, Alexia Adrianne ; Pereira, Samuel Santos ; Castro-Amarante, Maria Fernanda ; Rodrigues-Jesus, Monica Josiane ; de Pinho Favaro, Marianna Teixeira ; Chura-Chambi, Rosa Maria ; Morganti, Ligia ; de Souza Ferreira, Luis Carlos

• Document type: Journal article
• Source: FRONTIERS IN MEDICAL TECHNOLOGY; v. 2, p. 14-pg., 2020-12-03.

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-Barre 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. (AU)

• FAPESP's process: 14/17595-0 - New vaccine research based on recombinant proteins of dengue virus
• Grantee: Luis Carlos de Souza Ferreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/20045-7 - Antigen discovery and development of serological diagnostic methods and vaccine approaches against the Zika Virus (ZIKV)
• Grantee: Luis Carlos de Souza Ferreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/23560-0 - Development of uniplex and multiplex diagnostic platforms for arbovirus infection using recombinant proteins
• Grantee: Robert Andreata Santos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/14459-9 - Investigation of zika virus (ZIKV) antigens to develop serological tests and vaccine approaches
• Grantee: Maria Fernanda de Castro Amarante
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/05570-8 - Use of Zika virus recombinant proteins for development of diagnostic methods and vaccines
• Grantee: Lennon Ramos Pereira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/08199-4 - Nanovaccines: a novel experimental concept applied to the development of subunit vacines.
• Grantee: Marianna Teixeira de Pinho Favaro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/09661-0 - Development of new serological diagnostic strategies for typing prior Dengue virus infection
• Grantee: Samuel Santos Pereira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/14344-1 - Control tumors induced by HPV -based immunotherapy in combination monoclonal antibodies blocking immunosuppressive pathways a therapeutic vaccine capable of activating CD8 + cytotoxic T lymphocytes
• Grantee: Natiely Silva Sales
• Support Opportunities: Scholarships in Brazil - Doctorate