title: Multi-walled carbon nanotubes functionalized with recombinant Dengue virus 3 envelope proteins induce significant and specific immune responses in mice.
abstract: BACKGROUND
  Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue.
  
  
  METHODS
  The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model.
  
  
  RESULTS
  Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E.
  
  
  CONCLUSIONS
  Despite the recent licensure of the CYD-TDV dengue vaccine in some countries, results from the vaccine's phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.
authors.affiliation: Laboratory of Basic and Applied Virology, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Alice F
authors.initials: AF
authors.lastname: Versiani
authors.affiliation: Laboratory of Basic and Applied Virology, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Ruiz G
authors.initials: RG
authors.lastname: Astigarraga
authors.affiliation: Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Eliseu S O
authors.initials: ES
authors.lastname: Rocha
authors.affiliation: Laboratório de Nanoscopia, Departamento de Física, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Ana Paula M
authors.initials: AP
authors.lastname: Barboza
authors.affiliation: Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Erna G
authors.initials: EG
authors.lastname: Kroon
authors.affiliation: Departamento de Patologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Milene A
authors.initials: MA
authors.lastname: Rachid
authors.affiliation: Laboratory of Microorganism-Host Interaction, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Daniele G
authors.initials: DG
authors.lastname: Souza
authors.affiliation: Departamento de Física, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Luiz O
authors.initials: LO
authors.lastname: Ladeira
authors.affiliation: Laboratory of Basic and Applied Virology, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Edel F
authors.initials: EF
authors.lastname: Barbosa-Stancioli
authors.affiliation: Laboratório de Nanoscopia, Departamento de Física, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Ado
authors.initials: A
authors.lastname: Jorio
authors.affiliation: Laboratory of Basic and Applied Virology, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. fdafonseca@icb.ufmg.br.
authors.forename: Flávio G
authors.initials: FG
authors.lastname: Da Fonseca
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000276:immunology* / Q000627:therapeutic use; D003716:Dengue Virus / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D058726:Nanoconjugates / Q000737:chemistry; D050997:Nanomedicine; D037742:Nanotubes, Carbon / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D013059:Spectrum Analysis, Raman; D013154:Spleen / Q000166:cytology; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D053059:Dengue Vaccines; D007074:Immunoglobulin G; D058726:Nanoconjugates; D037742:Nanotubes, Carbon; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins
keywords: Carbon nanotubes; Dengue vaccine; Nanoconjugate; Subunit vaccine