title: Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice.
abstract: Virus-like particles are a highly effective type of subunit vaccine that mimics the overall structure of virus particles without containing infectious genetic material. In this work, a particulate form of the recombinant capsid protein from dengue-2 was evaluated in mice to determine the level of protection against viral challenge and to measure the antigen-induced cell-mediated immunity (CMI). The nucleocapsid-like particles (NLPs) adjuvanted with alum did not induce antiviral antibodies. However, splenocytes from the immunized animals secreted high levels of IFN-gamma upon virus stimulation, and a significant protection rate was achieved after challenge with lethal dengue-2 virus. Finally, both IFN-gamma secretion and protection against viral encephalitis were demonstrated to be dependent on CD4(+) and CD8(+) cells. This study provides new evidences regarding the protective role of the CMI in the mouse model without the induction of neutralizing antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease.
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Playa, Havana, Cuba. lazaro.gil@cigb.edu.cu
authors.forename: Lázaro
authors.initials: L
authors.lastname: Gil
authors.forename: Carlos
authors.initials: C
authors.lastname: López
authors.forename: Laura
authors.initials: L
authors.lastname: Lazo
authors.forename: Iris
authors.initials: I
authors.lastname: Valdés
authors.forename: Ernesto
authors.initials: E
authors.lastname: Marcos
authors.forename: Ruby
authors.initials: R
authors.lastname: Alonso
authors.forename: Ailyn
authors.initials: A
authors.lastname: Gambe
authors.forename: Jorge
authors.initials: J
authors.lastname: Martín
authors.forename: Yaremis
authors.initials: Y
authors.lastname: Romero
authors.forename: María G
authors.initials: MG
authors.lastname: Guzmán
authors.forename: Gerardo
authors.initials: G
authors.lastname: Guillén
authors.forename: Lisset
authors.initials: L
authors.lastname: Hermida
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019251:Nucleocapsid / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D053059:Dengue Vaccines; D011994:Recombinant Proteins; D007371:Interferon-gamma