THE JOURNAL OF GENE MEDICINE RESEARCH ARTICLE J Gene Med 2010; 12: 107–116. Published online 28 October 2009 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/jgm.1407 Immunization with a DNA vaccine candidate in chronic hepatitis C patients is safe, well tolerated and does not impair immune response induction after anti-hepatitis B vaccination Marlen Castellanos 1 Zurina Cinza 2 Zaily Dorta 1 Gloria Veliz 2 H´ ector Vega 1 Irma Lorenzo 1 Sergio Ojeda 1 Santiago Due˜ nas-Carrera 2 * Liz Alvarez-Lajonchere 2 Gillian Mart´ ınez 2 Elena Ferrer 1 Miladys Limonta 2 Marbelis Linares 2 Odalis Ruiz 2 Boris Acevedo 2 Dinorah Torres 2 Gabriel M´ arquez 2 Luis Herrera 2 Enrique Ar´ us 1 1 Instituto Nacional de Gastroenterolog´ ıa, Havana City, Cuba 2 Centro de Ingenier´ ıa Gen´ etica y Biotecnolog´ ıa, Havana, Cuba *Correspondence to: Santiago Due˜ nas-Carrera, Vaccine Division, Centro de Ingenier´ ıa Gen´ etica y Biotecnolog´ ıa, Ave 31, 58 and 190, Playa, PO Box 6162, Havana, Cuba. E-mail: santiago.duenas@cigb.edu.cu Received: 30 April 2009 Revised: 1 August 2009 Accepted: 4 September 2009 Abstract Background In the present study, we evaluated the safety of CIGB-230, a novel vaccine candidate based on the mixture of a plasmid for DNA immunization, expressing hepatitis C virus (HCV) structural antigens, with a recombinant HCV Core protein. Methods Fifteen HCV chronically-infected volunteers with detectable levels of HCV RNA genotype 1b, who were nonresponders to previous treatment with interferon plus ribavirin, were intramuscularly injected with CIGB-230 on weeks 0, 4, 8, 12, 16 and 20. Individuals were also immunized at weeks 28, 32 and 36 with a recombinant vaccine against hepatitis B. Adverse events were recorded and analyzed. Blood samples were taken every 4 weeks up to month 12 for hematological, biochemical, virological and immunological analysis. Results All patients completed the treatment with CIGB-230. Adverse events were only slight (83.6%) or moderate (16.4%). No significant differences in hematological and biochemical parameters, including serum aminotransferases, were detected between the baseline and post-treatment state. Induction of a CD4+ T lymphocyte response against a particular region in HCV E1, spanning amino acids 230 – 312 in HCV polyprotein, was detected in 42.8% of patients during treatment with CIGB-230. The ability of T cells to proliferate in response to mitogenic stimulation was not weakened. Most individuals (78.6%) were seroprotected after anti-hepatitis B vaccination and 42.8% were hyper-responders (antibody titers > 100 UI/ml). No anti- mitochondrial, anti-nuclear and anti-extractable nuclear antigen antibodies were generated during immunization with CIGB-230. Conclusions Vaccination with CIGB-230 in HCV chronically-infected individuals was safe, well tolerated and did not impair the ability to respond to non-HCV antigens. Copyright  2009 John Wiley & Sons, Ltd. Keywords adverse event; clinical trial; hepatitis C; plasmid; transaminases Introduction Hepatitis C virus (HCV) represents a major public health problem as a causative agent in developing chronic hepatitis, cirrhosis and hepatocellular Copyright  2009 John Wiley & Sons, Ltd.