title: HCV-specific immune responses induced by CIGB-230 in combination with IFN-α plus ribavirin.
abstract: OBJECTIVE
  To analyze hepatitis C virus (HCV)-specific immune responses in chronically infected patients under triple therapy with interferon-α (IFN-α) plus ribavirin and CIGB-230.
  
  
  METHODS
  CIGB-230 was administered in different schedules with respect to IFN-α plus ribavirin therapy. Paired serum and peripheral blood mononuclear cells (PBMC) samples from baseline and end of treatment were analyzed. The HCV-specific humoral response was tested by enzyme-linked immunosorbent assay, neutralizing antibodies were evaluated by cell culture HCV neutralization assays, PBMC proliferation was assayed by carboxyfluorescein succinimidyl ester staining and IFN-γ secretion was assessed by enzyme-linked immunospot. Data on virological and histological response and their association with immune variables are also provided.
  
  
  RESULTS
  From week 12 to week 48, all groups of patients showed a significant reduction in mean leukocyte counts. Statistically significant reductions in antibody titers were frequent, but only individuals immunized with CIGB-230 as early add-on treatment sustained the core-IgG response, and the neutralizing antibody response was enhanced only in patients receiving CIGB-230. Cell-mediated immune responses also tended to decline, but significant reductions in IFN-γ secretion and total absence of core-specific lymphoproliferation were exclusive of the control group. Only CIGB-230-immunized individuals showed de novo induced lymphoproliferative responses against the structural antigens. Importantly, it was demonstrated that the quality of the CIGB-230-induced immune response depended on the number of doses and timing of administration in relation to the antiviral therapy. Specifically, the administration of 6 doses of CIGB-230 as late add-on to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γ secretion, both of which were associated with the sustained virological response.
  
  
  CONCLUSIONS
  CIGB-230, combined with IFN-α-based therapy, modifies the immune response in chronic patients. The study provides evidence for the design of more effective therapeutic vaccine interventions against HCV.
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Yalena
authors.initials: Y
authors.lastname: Amador-Cañizares
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Gillian
authors.initials: G
authors.lastname: Martínez-Donato
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Liz
authors.initials: L
authors.lastname: Alvarez-Lajonchere
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Claudia
authors.initials: C
authors.lastname: Vasallo
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Mariacarla
authors.initials: M
authors.lastname: Dausá
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Daylen
authors.initials: D
authors.lastname: Aguilar-Noriega
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Carmen
authors.initials: C
authors.lastname: Valenzuela
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Ivette
authors.initials: I
authors.lastname: Raíces
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Jean
authors.initials: J
authors.lastname: Dubuisson
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Czeslaw
authors.initials: C
authors.lastname: Wychowski
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Zurina
authors.initials: Z
authors.lastname: Cinza-Estévez
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Marlén
authors.initials: M
authors.lastname: Castellanos
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Magdalys
authors.initials: M
authors.lastname: Núñez
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Anny
authors.initials: A
authors.lastname: Armas
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Yaimé
authors.initials: Y
authors.lastname: González
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Ismariley
authors.initials: I
authors.lastname: Revé
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Ivis
authors.initials: I
authors.lastname: Guerra
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Angel
authors.initials: A
authors.lastname: Pérez Aguiar
authors.affiliation: Yalena Amador-Cañizares, Gillian Martínez-Donato, Liz Álvarez-Lajonchere, Claudia Vasallo, Mariacarla Dausá, Daylen Aguilar-Noriega, Carmen Valenzuela, Ivette Raíces, Zurina Cinza-Estévez, Ismariley Revé, Ivis Guerra, Ángel Pérez Aguiar, Santiago Dueñas-Carrera, Centro de Ingeniería Genética y Biotecnología, Playa 10600, Havana, Cuba.
authors.forename: Santiago
authors.initials: S
authors.lastname: Dueñas-Carrera
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D003462:Cuba; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000097:blood; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007115:Immunization Schedule; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; C000589562:CIGB-230 vaccine; D018937:Hepatitis C Antibodies; C573415:IFNG protein, human; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; D012254:Ribavirin; D007371:Interferon-gamma
keywords: Clinical trial; DNA vaccine; Enzyme-linked immunospot; Hepatitis C virus; Leukopenia