title: Tetravalent dengue DIIIC protein together with alum and ODN elicits a Th1 response and neutralizing antibodies in mice.
abstract: Dengue disease is a global challenge for healthcare systems particularly during outbreaks, and millions of dollars are spent every year for vector control. An efficient and safe vaccine that is cost-effective could resolve the burden that dengue virus imposes on affected countries. We describe here the immunogenicity of a tetravalent formulation of a recombinant fusion protein consisting of E domain III and the capsid protein of dengue serotypes 1-4 (Tetra DIIIC). E domain III is an epitope for efficient neutralizing antibodies while the capsid protein contains T cell epitopes. Besides combining B and T cell epitopes, Tetra DIIIC is highly immunogenic due to its aggregate form and a two-component adjuvant. Following previous studies assessing the monovalent DIIIC formulations, we addressed here the quality and breadth of the T cell- and antibody response of Tetra DIIIC in mice. Tetra DIIIC induced a Th1-type response against all four DENV serotypes and dengue-specific antibodies were predominantly IgG1 and IgG2a and neutralizing, while the induction of neutralizing antibodies was dependent on IFN signaling. Importantly, the Th1 and IgG1/IgG2a profile of the DIIIC vaccine approach is similar to an efficient natural anti-dengue response.
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research A*STAR, Biopolis, 138648 Singapore, Singapore.
authors: Roland
authors: R
authors: Zuest
authors: Center for Genetic Engineering and Biotechnology, Havana City 10600, Cuba.
authors: Iris
authors: I
authors: Valdes
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research A*STAR, Biopolis, 138648 Singapore, Singapore.
authors: David
authors: D
authors: Skibinski
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research A*STAR, Biopolis, 138648 Singapore, Singapore.
authors: Yufang
authors: Y
authors: Lin
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research A*STAR, Biopolis, 138648 Singapore, Singapore.
authors: Ying Xiu
authors: YX
authors: Toh
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research A*STAR, Biopolis, 138648 Singapore, Singapore.
authors: Katherine
authors: K
authors: Chan
authors: Center for Genetic Engineering and Biotechnology, Havana City 10600, Cuba.
authors: Lisset
authors: L
authors: Hermida
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research A*STAR, Biopolis, 138648 Singapore, Singapore.
authors: John
authors: J
authors: Connolly
authors: Center for Genetic Engineering and Biotechnology, Havana City 10600, Cuba.
authors: Gerardo
authors: G
authors: Guillen
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research A*STAR, Biopolis, 138648 Singapore, Singapore. Electronic address: katja_fink@immunol.a-star.edu.sg.
authors: Katja
authors: K
authors: Fink
mesh_terms: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D003715:Dengue / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007372:Interferons / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology; D065288:Serogroup; D018417:Th1 Cells / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D053059:Dengue Vaccines; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D007372:Interferons
keywords: Alum; Antibodies; Dengue; ODN; Recombinant protein; T cell response; Th1; Vaccine