title: The protein DIIIC-2, aggregated with a specific oligodeoxynucleotide and adjuvanted in alum, protects mice and monkeys against DENV-2.
abstract: Previously, we reported the ability of the chimeric protein DIIIC-2 (domain III of the dengue envelope protein fused to the capsid protein of dengue-2 virus), to induce immunity and protection in mice, when it is highly aggregated with a non-defined oligodeoxynucleotide (ODN) and adjuvanted in alum. In this work, three different defined ODNs were studied as aggregating agents. Our results suggest that the nature of the ODN influences the capacity of protein DIIIC-2 to activate cell-mediated immunity in mice. Consequently, the ODN 39M was selected to perform further experiments in mice and nonhuman primates. Mice receiving the preparation 39M-DIIIC-2 were solidly protected against dengue virus (DENV) challenge. Moreover, monkeys immunized with the same preparation developed neutralizing antibodies, as measured by four different neutralization tests varying the virus strains and the cell lines used. Two of the immunized monkeys were completely protected against challenge, whereas the third animal had a single day of low-titer viremia. This is the first work describing the induction of short-term protection in monkeys by a formulation that is suitable for human use combining a recombinant protein from DENV with alum.
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Lázaro
authors.initials: L
authors.lastname: Gil
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Marcos
authors.affiliation: Virology Department, Tropical Medicine Institute 'Pedro Kourí', PAHO/WHO Collaborating Center for the study of Dengue and its vector, Havana, Cuba.
authors.forename: Alienys
authors.initials: A
authors.lastname: Izquierdo
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Laura
authors.initials: L
authors.lastname: Lazo
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Havana, 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, 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, Nairobi, Kenya.
authors.forename: Lucy
authors.initials: L
authors.lastname: Ochola
authors.affiliation: Department of Tropical and Infectious Diseases, Institute of Primate Research, National Museum of Kenya, WHO Collaborating Center, Nairobi, Kenya.
authors.forename: Rikoi
authors.initials: R
authors.lastname: Hitler
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Edith
authors.initials: E
authors.lastname: Suzarte
authors.affiliation: Virology Department, Tropical Medicine Institute 'Pedro Kourí', PAHO/WHO Collaborating Center for the study of Dengue and its vector, Havana, Cuba.
authors.forename: Mayling
authors.initials: M
authors.lastname: Álvarez
authors.affiliation: Department of Tropical and Infectious Diseases, Institute of Primate Research, National Museum of Kenya, WHO Collaborating Center, Nairobi, Kenya.
authors.forename: Prisilla
authors.initials: P
authors.lastname: Kimiti
authors.affiliation: Department of Tropical and Infectious Diseases, Institute of Primate Research, National Museum of Kenya, WHO Collaborating Center, Nairobi, Kenya.
authors.forename: James
authors.initials: J
authors.lastname: Ndung'u
authors.affiliation: Department of Tropical and Infectious Diseases, Institute of Primate Research, National Museum of Kenya, WHO Collaborating Center, 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, Havana, Cuba.
authors.forename: María Guadalupe
authors.initials: MG
authors.lastname: Guzmán
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Guillén
authors.affiliation: Vaccines Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
authors.forename: Lisset
authors.initials: L
authors.lastname: Hermida
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000097:blood; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D002522:Chlorocebus aethiops; D003715:Dengue / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D003716:Dengue Virus / Q000737:chemistry / Q000276:immunology*; D005260:Female; D005427:Flocculation; D015870:Gene Expression; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D053059:Dengue Vaccines; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C041524:aluminum sulfate