title: Recombinant nucleocapsid-like particles from dengue-2 induce functional serotype-specific cell-mediated immunity in mice.
abstract: The interplay of different inflammatory cytokines induced during dengue virus infection plays a role in either protection or increased disease severity. In this sense, vaccine strategies incorporating whole virus are able to elicit both functional and pathological responses. Therefore, an ideal tetravalent vaccine candidate against dengue should be focused on serotype-specific sequences. In the present work, a new formulation of nucleocapsid-like particles (NLPs) obtained from the recombinant dengue-2 capsid protein was evaluated in mice to determine the level of protection against homologous and heterologous viral challenge and to measure the cytotoxicity and cytokine-secretion profiles induced upon heterologous viral stimulation. As a result, a significant protection rate was achieved after challenge with lethal dengue-2 virus, which was dependent on CD4(+) and CD8(+) cells. In turn, no protection was observed after heterologous challenge. In accordance, in vitro-stimulated spleen cells from mice immunized with NLPs from the four dengue serotypes showed a serotype-specific response of gamma interferon- and tumour necrosis factor alpha-secreting cells. A similar pattern was detected when spleen cells from dengue-immunized animals were stimulated with the capsid protein. Taking these data together, we can assert that NLPs constitute an attractive vaccine candidate against dengue. They induce a functional immune response mediated by CD4(+) and CD8(+) cells in mice, which is protective against viral challenge. In turn, they are potentially safe due to two important facts: induction of serotype specific cell-mediated immunity and lack of induction of antiviral 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 (CIGB), Avenue 31, PO Box 6162, Playa, Havana 10 600, Cuba.
authors.forename: Lázaro
authors.initials: L
authors.lastname: Gil
authors.affiliation: Virology Department, Tropical Medicine Institute 'Pedro Kourí', PAHO/WHO Collaborating Center for the Study of Dengue and its Vector, Autopista Novia del Mediodía, km 6� PO Box Marianao 13, Havana 11 600, Cuba.
authors.forename: Lídice
authors.initials: L
authors.lastname: Bernardo
authors.affiliation: Virology Department, Tropical Medicine Institute 'Pedro Kourí', PAHO/WHO Collaborating Center for the Study of Dengue and its Vector, Autopista Novia del Mediodía, km 6� PO Box Marianao 13, Havana 11 600, Cuba.
authors.forename: Alequis
authors.initials: A
authors.lastname: Pavón
authors.affiliation: Virology Department, Tropical Medicine Institute 'Pedro Kourí', PAHO/WHO Collaborating Center for the Study of Dengue and its Vector, Autopista Novia del Mediodía, km 6� PO Box Marianao 13, Havana 11 600, Cuba.
authors.forename: Alienys
authors.initials: A
authors.lastname: Izquierdo
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, PO Box 6162, Playa, Havana 10 600, Cuba.
authors.forename: Iris
authors.initials: I
authors.lastname: Valdés
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, PO Box 6162, Playa, Havana 10 600, Cuba.
authors.forename: Laura
authors.initials: L
authors.lastname: Lazo
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, PO Box 6162, Playa, Havana 10 600, Cuba.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Marcos
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, PO Box 6162, Playa, Havana 10 600, Cuba.
authors.forename: Yaremis
authors.initials: Y
authors.lastname: Romero
authors.affiliation: Virology Department, Tropical Medicine Institute 'Pedro Kourí', PAHO/WHO Collaborating Center for the Study of Dengue and its Vector, Autopista Novia del Mediodía, km 6� PO Box Marianao 13, Havana 11 600, Cuba.
authors.forename: María G
authors.initials: MG
authors.lastname: Guzmán
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, PO Box 6162, Playa, Havana 10 600, Cuba.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Guillén
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, PO Box 6162, Playa, Havana 10 600, Cuba.
authors.forename: Lisset
authors.initials: L
authors.lastname: Hermida
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D003716:Dengue Virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019251:Nucleocapsid / Q000235:genetics / Q000276:immunology; D013045:Species Specificity; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma