32 This technique has been used in cancer patients,33 and has been found to raise T cell responses to HCV in chimpanzees.34 Another question is which antigens should be used. Ideally, the antigen should be highly expressed in infected cells, and selleck chem Paclitaxel represent a well-conserved viral region so that the vaccine-primed T cells will recognize endogenous virus. A recent meta-analysis suggested that the best antigens to use in a protective vaccine would be the structural antigens.35 Since these are often highly variable and may be less suitable in therapeutic vaccines. The most conserved HCV genes are the core, nonstructural (NS) 3 and NS5B genes,7 which suggests that these are suitable for inclusion in therapeutic vaccines.

In the current study, we initiated a small proof-of-concept study to investigate whether a therapeutic HCV vaccination has an impact on the immune response and whether vaccination has any influence on a subsequent standard-of-care (SOC) treatment in patients with chronic HCV infection. Results Safety and tolerability of DNA vaccination delivered by in vivo EP All patients tolerated the vaccine injections well and no major side effects were noted. Within a minute after the vaccine injection, EP was performed at the same site. The correct delivery of the EP pulses could easily be discerned by two small muscle twitches in the vaccinated arm. A short-lasting pain was recorded that waned within a few minutes. Subjects receiving the EP procedure described the experience qualitatively as ��leaving a small feeling of having been hit��. The perceived pain level has been illustrated in Figure 1.

During and after the EP procedures, patients stayed in the hospital for 2 hours. No major adverse event beside the transient pain was noted. In vivo EP was the cause for the transient local pain. The pain was immediate at administration of the electrical pulses. On a relative 10-level pain scale the in vivo EP gave scores ranging from 2 to 8 whereas the DNA injection gave a score from 0 to 5 (Figure 1; P < 0.01, Mann�CWhitney U-test). The perceived pain did not increase with repeated doses of the DNA vaccine (Figure 1). No significant change in blood chemistry was noted related to the treatment (data not shown). No severe adverse event was seen. Figure 1 Pain levels recorded immediately after in vivo electroporation (EP) given in relation to the pain level related to the DNA injection.

Values are summarized from all four treatments and have been given as the mean pain level estimated using the visual … DNA vaccination induces a transient HCV-specific AV-951 T cell activation The second endpoint of the study was immunogenicity. This was determined both on the B and T cell level. The levels of anti-NS3 IgG were quantified in all samples. The mean endpoint titers did not change significantly during the vaccinations due to high levels of pre-existing antibodies in all patients (data not shown).