title: Capsid protein: evidences about the partial protective role of neutralizing antibody-independent immunity against dengue in monkeys.
abstract: The role of cellular immune response in dengue virus infection is not yet fully understood. Only few studies in murine models propose that CD8(+) T-cells are associated with protection from infection and disease. At the light of recent reports about the protective role of CD8(+) T-cells in humans and the no correlation between neutralizing antibodies and protection observed in several studies, a vaccine based on cell-mediated immunity constitute an attractive approach. Our group has developed a capsid-based vaccine as nucleocpasid-like particles from dengue-2 virus, which induced a protective CD4(+) and CD8(+) cell-mediated immunity in mice, without the contribution of neutralizing antibodies. Herein we evaluated the immunogenicity and protective efficacy of this molecule in monkeys. Neither IgG antibodies against the whole virus nor neutralizing antibodies were elicited after the antigen inoculation. However, animals developed a cell-mediated immunity, measured by gamma interferon secretion and cytotoxic capacity. Although only one out of three vaccinated animals was fully protected against viral challenge, a viral load reduction was observed in this group compared with the placebo one, suggesting that capsid could be the base on an attractive vaccine against dengue.
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Ave. 31, PO Box 6162, Playa, Havana 10600, 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 6½ PO Box Marianao 13, Havana 11600, Cuba.
authors.forename: Alienys
authors.initials: A
authors.lastname: Izquierdo
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Ave. 31, PO Box 6162, Playa, Havana 10600, Cuba.
authors.forename: Laura
authors.initials: L
authors.lastname: Lazo
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Ave. 31, PO Box 6162, Playa, Havana 10600, Cuba.
authors.forename: Iris
authors.initials: I
authors.lastname: Valdés
authors.affiliation: Department of Tropical and Infectious Diseases, Institute of Primate Research, National Museum of Kenya, WHO Collaborating Center, PO Box 24481 Karen, Nairobi, Kenya.
authors.forename: Peris
authors.initials: P
authors.lastname: Ambala
authors.affiliation: Department of Tropical and Infectious Diseases, Institute of Primate Research, National Museum of Kenya, WHO Collaborating Center, PO Box 24481 Karen, Nairobi, Kenya.
authors.forename: Lucy
authors.initials: L
authors.lastname: Ochola
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Ave. 31, PO Box 6162, Playa, Havana 10600, Cuba.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Marcos
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Ave. 31, PO Box 6162, Playa, Havana 10600, Cuba.
authors.forename: Edith
authors.initials: E
authors.lastname: Suzarte
authors.affiliation: Department of Tropical and Infectious Diseases, Institute of Primate Research, National Museum of Kenya, WHO Collaborating Center, PO Box 24481 Karen, Nairobi, Kenya.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kariuki
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 6½ PO Box Marianao 13, Havana 11600, Cuba.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Guzmán
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Ave. 31, PO Box 6162, Playa, Havana 10600, Cuba.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Guillén
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Ave. 31, PO Box 6162, Playa, Havana 10600, Cuba. Electronic address: lisset.hermida@cigb.edu.cu.
authors.forename: Lisset
authors.initials: L
authors.lastname: Hermida
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology; D002522:Chlorocebus aethiops; D003602:Cytotoxicity, Immunologic; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D019562:Viral Load
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D053059:Dengue Vaccines; D022223:Vaccines, Subunit; D007371:Interferon-gamma
keywords: Capsid protein; Dengue-2 virus; Nonhuman primates; Nucleocapsid-like particles; Protection