Antigenicity of a recombinant NS3 protein representative of ATPase/helicase domain from hepatitis C virus

Pentón, Nancy; Musacchio, Andrea; Rivera, Juan M; Roca, Juan; Ponce, Milagros; Rodríguez, D; Caballero, Armando R.; Tallo, Y.I; Narciandi, R. E.

doi:10.1016/s0009-9120(02)00365-x

Cited by 2 publications

(2 citation statements)

References 47 publications

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“…To detect human antibodies to HCV structural antigens, 96‐well microtiter plates (Costar, Cambridge, MA, USA) were coated with 100 μL of Co.120 [24], E1.340 [25] 10 μg/mL or NS3 [26] 5 μg/mL diluted in coating buffer (50 m m carbonate buffer, pH 9.6) followed by overnight incubation at 4 ºC. For detection of antibodies against HVR‐I [27], the 96‐well microtitre plates were coated with a synthetic peptide covering aa 384‐414 of the HCV polyprotein, homologous to the sequence present in the vaccine candidate, 2 μg/mL in the same conditions.…”

Section: Methodsmentioning

confidence: 99%

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

Alvarez‐Lajonchere

Shoukry

Gra

et al. 2009

Journal of Viral Hepatitis

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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.

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Section: Methodsmentioning

confidence: 99%

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

Alvarez‐Lajonchere

Shoukry

Gra

et al. 2009

Journal of Viral Hepatitis

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“…The recombinant proteins Co.120 [23] , E1.340 [24] and NS3 [25] are expressed in modified Escherichia coli and purified to 90%, except E1.340 which is purified to 85%. E2.680 recombinant protein is expressed in modified Picchia pastoris yeast and purified to 85% [26] .…”

Section: Antigensmentioning

confidence: 99%

Induction of IgA and sustained deficiency of cell proliferative response in chronic hepatitis C

Amador-Cañizares¹,

Alvarez‐Lajonchere²,

Guerra³

et al. 2008

WJG

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AIM:In the present study, antibody and peripheral b l o o d m o n o n u c l e a r c e l l s ( P B M C ) p r o l i fe ra t i ve responses against hepatitis C virus (HCV) antigens were evaluated in HCV chronically infected patients. ME THOD S : Pa i r e d s e r u m a n d P B M C s a m p l e s were taken six months apart from 34 individuals, either treated or not, and tested by enzyme-linked immunosorbent assay (ELISA) and carboxyfluorescein succinimidyl ester staining. RESULTS: Over 70% of the patients showed specific IgG and IgM against capsid, E1 and NS3, while HVR-1 was recognized by half of the patients. An increase in the levels of the anti-capsid IgM (P = 0.027) and IgG (P = 0.0006) was observed in six-month samples, compared to baseline. Similarly, a significantly higher percent of patients had detectable IgA reactivity to capsid (P = 0.017) and NS3 (P = 0.005) after six months, compared to baseline. Particularly, IgA against structural antigens positively correlated with hepatic damage (P = 0.036). IgG subclasses evaluation against capsid and NS3 revealed a positive recognition mediated by IgG1 in more than 80% of the individuals. On the contrary, less than 30% of the patients showed a positive proliferative response either of CD4+ or CD8+ T cells, being the capsid poorly recognized. CONCLUSION: These results confirm that while the cellular immune response is narrow and weak, a broad and vigorous humoral response occurs in HCV chronic infection. The observed correlation between IgA and hepatic damage may have diagnostic significance, although it warrants further confirmation.

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Antigenicity of a recombinant NS3 protein representative of ATPase/helicase domain from hepatitis C virus

Cited by 2 publications

References 47 publications

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

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

Induction of IgA and sustained deficiency of cell proliferative response in chronic hepatitis C

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