title: Targeting of envelope domain III protein of DENV type 2 to DEC-205 receptor elicits neutralizing antibodies in mice.
abstract: Dengue virus (DENV) is the causal agent of severe disease and, in some cases, mortality in humans, but no licensed vaccines against dengue are available. An effective vaccine against dengue requires long-term humoral and cellular immune responses. Several viral proteins have been the subjects of intense research, especially the envelope (E) protein, aimed at developing a vaccine. Domain III of the envelope protein (EDIII) has been identified as a potential candidate because it is involved in binding to host cell receptors and contains epitopes that elicit virus neutralizing antibodies. However, this domain is not sufficiently antigenic when is expressed and administered as antigen to elicit a strong immune response. One alternative to enhance immunogenicity is to target the antigen to dendritic cells to induce T-cells for broad antibody responses. In this work, a single chain antibody fragment (scFv) raised against the DEC-205 receptor fused with the EDIII was successfully expressed in Nicotiana benthamiana. The recombinant protein was expressed and purified from the plant and evaluated in BALB/c mice to test its immunogenicity and ability to induce neutralizing antibodies against DENV. The mice immunized with the recombinant protein produced specific and strong humoral immune responses to DENV. Only two immunizations were required to generate a memory response to DENV without the presence of adjuvants. Also, recognition of the recombinant protein with sera from DENV-infected patients was observed. These findings suggest that this strategy has potential for development of an effective vaccine against DENV.
authors.affiliation: Departamento de Ingeniería Genética, CINVESTAV-IPN, Km 9.6 carretera Irapuato-León, C.P. 36821 Irapuato, Guanajuato, Mexico. coconi linares@yahoo.com
authors.forename: Nancy
authors.initials: N
authors.lastname: Coconi-Linares
authors.forename: Enrique
authors.initials: E
authors.lastname: Ortega-Dávila
authors.forename: Moisés
authors.initials: M
authors.lastname: López-González
authors.forename: Jazmín
authors.initials: J
authors.lastname: García-Machorro
authors.forename: Julio
authors.initials: J
authors.lastname: García-Cordero
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Leticia
authors.initials: L
authors.lastname: Cedillo-Barrón
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gómez-Lim
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology / Q000378:metabolism; D000917:Antibody Formation; D015703:Antigens, CD / Q000276:immunology*; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015703:Antigens, CD; C093569:DEC-205 receptor; D053059:Dengue Vaccines; D000939:Epitopes; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins