Immunogenicity of CIGB-230, a therapeutic DNA vaccine preparation, in HCV-chronically infected individuals in a Phase I clinical trial

[Guest guest]

J Viral Hepat. 2008 Oct 31. [Epub ahead of print]

Immunogenicity of CIGB-230, a therapeutic DNA vaccine preparation, in

HCV-chronically infected individuals in a Phase I clinical trial.

Alvarez-Lajonchere L, Shoukry NH, Grá B, Amador-Cañizares Y, Helle F, Bédard N,

Guerra I, Drouin C, Dubuisson J, González-Horta EE, Martínez G, Marante J, Cinza

Z, Castellanos M, Dueñas-Carrera S.

Centro de Ingeniería Genética y Biotecnología, Havana, Cuba.

Summary. Hepatitis C virus (HCV) is a worldwide health problem. No vaccine is

available against this pathogen and therapeutic treatments currently in use are

of limited efficacy. In the present study, the immunogenicity of the therapeutic

vaccine candidate CIGB-230, based on the mixture of pIDKE2, a plasmid expressing

HCV structural antigens, with a recombinant HCV core protein, Co.120, was

evaluated. CIGB-230 was administered by intramuscular injection on weeks 0, 4,

8, 12, 16 and 20 to 15 HCV-chronically infected individuals, non-responders to

previous treatment with interferon (IFN) plus ribavirin. Interestingly,

following the final immunization, neutralizing antibody responses against

heterologous viral pseudoparticles were modified in eight individuals, including

six de novo responders. In addition, 73% of vaccinees exhibited specific T cell

proliferative response and T cell IFN-gamma secretory response 24 weeks after

primary immunization with CIGB-230. Furthermore, 33.3% of individuals developed

de novo cellular immune response against HCV core and the number of patients

(46.7% at the end of treatment) with cellular immune response against more than

one HCV structural antigen increased during vaccination (P = 0.046). In

addition, despite persistent detection of HCV RNA, more than 40% percent of

vaccinated individuals improved or stabilized liver histology, particularly

reducing fibrosis, which correlated with cellular immune response against more

than one HCV antigen (P = 0.0053). In conclusion, CIGB-230 is a promising

candidate for effective therapeutic interventions based on its ability for

enhancing the immune response in HCV chronically infected individuals.

PMID: 19017255 [PubMed - as supplied by publisher]

[Guest guest]

J Viral Hepat. 2008 Oct 31. [Epub ahead of print]

Immunogenicity of CIGB-230, a therapeutic DNA vaccine preparation, in

HCV-chronically infected individuals in a Phase I clinical trial.

Alvarez-Lajonchere L, Shoukry NH, Grá B, Amador-Cañizares Y, Helle F, Bédard N,

Guerra I, Drouin C, Dubuisson J, González-Horta EE, Martínez G, Marante J, Cinza

Z, Castellanos M, Dueñas-Carrera S.

Centro de Ingeniería Genética y Biotecnología, Havana, Cuba.

Summary. Hepatitis C virus (HCV) is a worldwide health problem. No vaccine is

available against this pathogen and therapeutic treatments currently in use are

of limited efficacy. In the present study, the immunogenicity of the therapeutic

vaccine candidate CIGB-230, based on the mixture of pIDKE2, a plasmid expressing

HCV structural antigens, with a recombinant HCV core protein, Co.120, was

evaluated. CIGB-230 was administered by intramuscular injection on weeks 0, 4,

8, 12, 16 and 20 to 15 HCV-chronically infected individuals, non-responders to

previous treatment with interferon (IFN) plus ribavirin. Interestingly,

following the final immunization, neutralizing antibody responses against

heterologous viral pseudoparticles were modified in eight individuals, including

six de novo responders. In addition, 73% of vaccinees exhibited specific T cell

proliferative response and T cell IFN-gamma secretory response 24 weeks after

primary immunization with CIGB-230. Furthermore, 33.3% of individuals developed

de novo cellular immune response against HCV core and the number of patients

(46.7% at the end of treatment) with cellular immune response against more than

one HCV structural antigen increased during vaccination (P = 0.046). In

addition, despite persistent detection of HCV RNA, more than 40% percent of

vaccinated individuals improved or stabilized liver histology, particularly

reducing fibrosis, which correlated with cellular immune response against more

than one HCV antigen (P = 0.0053). In conclusion, CIGB-230 is a promising

candidate for effective therapeutic interventions based on its ability for

enhancing the immune response in HCV chronically infected individuals.

PMID: 19017255 [PubMed - as supplied by publisher]