title: Multi-walled carbon nanotubes increase antibody-producing B cells in mice immunized with a tetravalent vaccine candidate for dengue virus.
abstract: BACKGROUND
  In recent times, studies have demonstrated that carbon nanotubes are good candidates for use as vehicles for transfection of exogenous material into the cells. However, there are few studies evaluating the behavior of carbon nanotubes as DNA vectors and few of these studies have used multi-walled carbon nanotubes (MWCNTs) or carboxylated MWCNTs. Thus, this study aims to assess the MWCNTs' (carboxylated or not) efficiency in the increase in expression of the tetravalent vaccine candidate (TVC) plasmid vector for dengue virus in vitro using Vero cells, and in vivo, through the intramuscular route, to evaluate the immunological response profile.
  
  
  RESULTS
  Multi-walled carbon nanotubes internalized by Vero cells, have been found in the cytoplasm and nucleus associated with the plasmid. However, it was not efficient to increase the messenger ribonucleic acid (mRNA) compared to the pure vaccine candidate associated with Lipofectamine(®) 2000. The in vivo experiments showed that the use of intramuscular injection of the TVC in combination with MWCNTs reduced the immune response compared to pure TVC, in a general way, although an increase was observed in the population of the antibody-producing B cells, as compared to pure TVC.
  
  
  CONCLUSIONS
  The results confirm the data found by other authors, which demonstrate the ability of nanotubes to penetrate target cells and reach both the cytoplasm and the cell nucleus. The cytotoxicity values are also in accordance with the literature, which range from 5 to 20 µg/mL. This has been found to be 10 µg/mL in this study. Although the expression levels are higher in cells that receive the pure TVC transfected using Lipofectamine(®) 2000, the nanotubes show an increase in B-cells producing antibodies.
authors.affiliation: Federal University of Viçosa, Avenida Peter Henry Rolfs, s/n, Campus Universitário, Viçosa, MG, 36570-900, Brazil.
authors.forename: Luan P
authors.initials: LP
authors.lastname: Calegari
authors.affiliation: Federal University of Viçosa, Avenida Peter Henry Rolfs, s/n, Campus Universitário, Viçosa, MG, 36570-900, Brazil.
authors.forename: Roberto S
authors.initials: RS
authors.lastname: Dias
authors.affiliation: Federal University of Viçosa, Avenida Peter Henry Rolfs, s/n, Campus Universitário, Viçosa, MG, 36570-900, Brazil.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: de Oliveira
authors.affiliation: Federal University of Viçosa, Avenida Peter Henry Rolfs, s/n, Campus Universitário, Viçosa, MG, 36570-900, Brazil.
authors.forename: Carine Ribeiro
authors.initials: CR
authors.lastname: Pessoa
authors.affiliation: Federal Institute of Education, Science and Technology of North of Minas Gerais, R. Gabriel Passos, 259, Centro, Montes Claros, MG, 39400-112, Brazil.
authors.forename: André S
authors.initials: AS
authors.lastname: de Oliveira
authors.affiliation: Federal Institute of Education, Science and Technology of North of Minas Gerais, R. Gabriel Passos, 259, Centro, Montes Claros, MG, 39400-112, Brazil.
authors.forename: Ana F C S
authors.initials: AF
authors.lastname: Oliveira
authors.affiliation: Federal University of Viçosa, Avenida Peter Henry Rolfs, s/n, Campus Universitário, Viçosa, MG, 36570-900, Brazil.
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: da Silva
authors.affiliation: Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Flavio G
authors.initials: FG
authors.lastname: Fonseca
authors.affiliation: Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Alice F
authors.initials: AF
authors.lastname: Versiani
authors.affiliation: Federal University of Viçosa, Avenida Peter Henry Rolfs, s/n, Campus Universitário, Viçosa, MG, 36570-900, Brazil. depaula@ufv.br.
authors.forename: Sérgio O
authors.initials: SO
authors.lastname: De Paula
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D002522:Chlorocebus aethiops; D003715:Dengue / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053059:Dengue Vaccines / Q000008:administration & dosage* / Q000276:immunology; D003716:Dengue Virus / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000494:pharmacology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D014162:Transfection / Q000379:methods*; D014611:Vaccination; D014709:Vero Cells
chemical_list: D000914:Antibodies, Viral; D053059:Dengue Vaccines; D008055:Lipids; C086724:Lipofectamine; D037742:Nanotubes, Carbon
keywords: Dengue; Intramuscular route; Multi-walled carbon nanotubes; Vaccine; Vero cells