Production of a Recombinant Dengue Virus 2 NS5 Protein and Potential Use as a Vaccine Antigen
| Autor: | Luís Carlos de Souza Ferreira, Denicar Lina Nascimento Fabris, Paolo Marinho de Andrade Zanotto, Lennon Ramos Pereira, Felipe Scassi Salvador, Rúbens Prince dos Santos Alves, Robert Andreata Santos, Camila Malta Romano, Jaime Henrique Amorim |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Microbiology (medical) viruses T cell 030106 microbiology Clinical Biochemistry Immunology Dengue Vaccines Viral Nonstructural Proteins Dengue virus Antibodies Viral medicine.disease_cause Epitope Virus Dengue fever Dengue Epitopes Mice 03 medical and health sciences Immune system Escherichia coli medicine Animals Humans Immunology and Allergy Computer Simulation Dengue vaccine Vaccines Immunity Cellular Mice Inbred BALB C biology virus diseases Dengue Virus medicine.disease Virology Recombinant Proteins 030104 developmental biology medicine.anatomical_structure biology.protein Antibody |
| Zdroj: | Clinical and Vaccine Immunology. 23:460-469 |
| ISSN: | 1556-679X 1556-6811 |
| Popis: | Dengue fever is caused by any of the four known dengue virus serotypes (DENV1 to DENV4) that affect millions of people worldwide, causing a significant number of deaths. There are vaccines based on chimeric viruses, but they still are not in clinical use. Anti-DENV vaccine strategies based on nonstructural proteins are promising alternatives to those based on whole virus or structural proteins. The DENV nonstructural protein 5 (NS5) is the main target of anti-DENV T cell-based immune responses in humans. In this study, we purified a soluble recombinant form of DENV2 NS5 expressed in Escherichia coli at large amounts and high purity after optimization of expression conditions and purification steps. The purified DENV2 NS5 was recognized by serum from DENV1-, DENV2-, DENV3-, or DENV4-infected patients in an epitope-conformation-dependent manner. In addition, immunization of BALB/c mice with NS5 induced high levels of NS5-specific antibodies and expansion of gamma interferon- and tumor necrosis factor alpha-producing T cells. Moreover, mice immunized with purified NS5 were partially protected from lethal challenges with the DENV2 NGC strain and with a clinical isolate (JHA1). These results indicate that the recombinant NS5 protein preserves immunological determinants of the native protein and is a promising vaccine antigen capable of inducing protective immune responses. |
| Databáze: | OpenAIRE |
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