title: DNA priming E and NS1 constructs--homologous proteins boosting immunization strategy to improve immune response against dengue in mice.
abstract: DNA priming-protein boosting is a strategy used to establish strong immunity to a specific pathogen by the use of two different antigens through sequential delivery systems. In this work, two recombinant plasmids were used, one encoding for the dengue virus E protein, which is know to induce neutralizing antibodies (pcDNA 3.1/E), and the other encoding for the Dengue virus nonstructural protein 1 (pcDNA 3.1/NS1), as a source of B- and T-cell epitopes possibly involved in protective immunity. We showed that immunization of BALB/c mice with three priming doses of both plasmids pcDNA 3.1/E and/or pcDNA 3.1/NS1 were able to induce antibody responses to E protein with a single plasmid; in contrast to the antibody response to NS1 protein we observed an additive effect in terms of antibody response. Moreover, using a prime-boost protocol in which both plasmid constructs were co-administrated followed by a boost of homologous GST-E and GST-NS1 recombinant proteins, we observed an increased antibody response to NS1 and to E protein compared to animals vaccinated with the proteins or with dengue constructs alone. If neutralizing antibodies play an important role in dengue infection, antibodies generated with this regimen was also significantly better than the administration of the mix of proteins alone. These results suggest that NS1 and E proteins together could be considered in a design of subunit recombinant vaccines.
authors.affiliation: Departamento de Biomedicina Molecular Centro de Investigación y Estudios Avanzadas del IPN, Mexico, DF Mexico.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Mellado-Sánchez
authors.forename: Julio
authors.initials: J
authors.lastname: García-Cordero
authors.forename: Rosendo
authors.initials: R
authors.lastname: Luria-Pérez
authors.forename: Lucero
authors.initials: L
authors.lastname: Lázaro-Olan
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Santos-Argumedo
authors.forename: Benito
authors.initials: B
authors.lastname: Gutiérrez-Castañeda
authors.forename: Iris
authors.initials: I
authors.lastname: Estrada-García
authors.forename: Leticia
authors.initials: L
authors.lastname: Cedillo-Barrón
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D005822:Genetic Vectors; D007115:Immunization Schedule; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010957:Plasmids; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; C051821:E-glycoprotein, Dengue virus type 2; C079340:NS1 protein, Dengue virus type 2; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines