title: Protective T Cell and Antibody Immune Responses against Hepatitis C Virus Achieved Using a Biopolyester-Bead-Based Vaccine Delivery System.
abstract: Hepatitis C virus (HCV) infection is a major worldwide problem. Chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocellular carcinoma, and liver failure. Although new, directly acting antiviral therapies are suggested to overcome the low efficacy and adverse effects observed for the current standard of treatment, an effective vaccine would be the only way to certainly eradicate HCV infection. Recently, polyhydroxybutyrate beads produced by engineered Escherichia coli showed efficacy as a vaccine delivery system. Here, an endotoxin-free E. coli strain (ClearColi) was engineered to produce polyhydroxybutyrate beads displaying the core antigen on their surface (Beads-Core) and their immunogenicity was evaluated in BALB/c mice. Immunization with Beads-Core induced gamma interferon (IFN-γ) secretion and a functional T cell immune response against the HCV Core protein. With the aim to target broad T and B cell determinants described for HCV, Beads-Core mixed with HCV E1, E2, and NS3 recombinant proteins was also evaluated in BALB/c mice. Remarkably, only three immunization with Beads-Core+CoE1E2NS3/Alum (a mixture of 0.1 μg Co.120, 16.7 μg E1.340, 16.7 μg E2.680, and 10 μg NS3 adjuvanted in aluminum hydroxide [Alum]) induced a potent antibody response against E1 and E2 and a broad IFN-γ secretion and T cell response against Core and all coadministered antigens. This immunological response mediated protective immunity to viremia as assessed in a viral surrogate challenge model. Overall, it was shown that engineered biopolyester beads displaying foreign antigens are immunogenic and might present a particulate delivery system suitable for vaccination against HCV.
authors.affiliation: Center for Genetic Engineering and Biotechnology, Vaccines Department, Havana, Cuba gillian.martinez@cigb.edu.cu.
authors.forename: G
authors.initials: G
authors.lastname: Martínez-Donato
authors.affiliation: Center for Genetic Engineering and Biotechnology, Vaccines Department, Havana, Cuba.
authors.forename: B
authors.initials: B
authors.lastname: Piniella
authors.affiliation: Center for Genetic Engineering and Biotechnology, Vaccines Department, Havana, Cuba.
authors.forename: D
authors.initials: D
authors.lastname: Aguilar
authors.affiliation: Center for Genetic Engineering and Biotechnology, Vaccines Department, Havana, Cuba.
authors.forename: S
authors.initials: S
authors.lastname: Olivera
authors.affiliation: Center for Genetic Engineering and Biotechnology, Vaccines Department, Havana, Cuba.
authors.forename: A
authors.initials: A
authors.lastname: Pérez
authors.affiliation: Center for Genetic Engineering and Biotechnology, Vaccines Department, Havana, Cuba.
authors.forename: Y
authors.initials: Y
authors.lastname: Castañedo
authors.affiliation: Center for Genetic Engineering and Biotechnology, Vaccines Department, Havana, Cuba.
authors.forename: L
authors.initials: L
authors.lastname: Alvarez-Lajonchere
authors.affiliation: Center for Genetic Engineering and Biotechnology, Vaccines Department, Havana, Cuba.
authors.forename: S
authors.initials: S
authors.lastname: Dueñas-Carrera
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: J W
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: N
authors.initials: N
authors.lastname: Burr
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand PolyBatics Ltd., Palmerston North, New Zealand.
authors.forename: M
authors.initials: M
authors.lastname: Gonzalez-Miro
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand PolyBatics Ltd., Palmerston North, New Zealand MacDiarmid Institute for Advanced Materials and Nanotechnology, Palmerston North, New Zealand.
authors.forename: B H A
authors.initials: BH
authors.lastname: Rehm
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000517:prevention & control; D018937:Hepatitis C Antibodies / Q000097:blood*; D006885:Hydroxybutyrates / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000378:metabolism; D060847:Metabolic Engineering; D008807:Mice, Inbred BALB C; D011091:Polyesters / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control; D000094122:Polyhydroxybutyrates
chemical_list: D018937:Hepatitis C Antibodies; D006885:Hydroxybutyrates; D007371:Interferon-gamma; D011091:Polyesters; D014765:Viral Vaccines; C003182:poly-beta-hydroxybutyrate; D000094122:Polyhydroxybutyrates