The reasons for the failed specific T cell activation after http://www.selleckchem.com/products/baricitinib-ly3009104.html the third and fourth vaccination are not clear. However, one may speculate that the vaccine currently has a suboptimal immunogenicity and therefore the primed responses are unable to permanently break the inhibition of the HCV-specific responses. Hence, repeated vaccination may therefore have no beneficial effects. Thus, similar studies using a vaccine with improved immunogenicity merits further investigation. In addition, it is also likely that the strong regulatory effects present in the chronic infection are difficult to overcome with the used vaccine alone. Furthermore, four vaccine doses with this vaccine alone were not sufficient to achieve sustained virological response by itself in patients with chronic HCV.

However, when combined with pegylated IFN and ribavirin treatment or in the future with DAAs,44 therapeutic vaccination possibly will have an influence on the response rates and clearance of HCV. In our small study, 75% of the vaccinated patients, all infected by HCV genotype 1, were cured with the subsequent SOC treatment, which is an encouraging result. However, with the development of highly effective HCV-targeted drugs, the role for a therapeutic vaccine is likely to be small. On the other hand, it is possible that some patient groups in need of alternative treatment options, may still benefit from therapeutic vaccines. Such groups could include patients resistant to DAAs, patients not eligible for DAA treatment, patients exposed to HCV repeatedly (e.g.

, injection drug users at risk of HCV re-infection), and patients in resource-poor environments. To be able to cure 100% of HCV-infected patients, it is not unlikely that successful HCV treatment for selected patients will consist of several DAAs used in combination with immune modulatory measures including therapeutic vaccines. In conclusion, the concept of therapeutic DNA vaccine delivered by in vivo EP to treat chronic HCV is safe and should be further investigated in combination with other compounds with different modes of action, and/or by further improving the immunogenicity. Materials and Methods Human subjects. This trial was approved by the Regional Ethical Council in Stockholm, Sweden and by the Swedish Medical Products Agency. The Declaration of Helsinki protocols were followed and all patients gave their written informed consent.

The trial has been registered at http://www.clinicaltrials.gov (http://clinicaltrials.gov/ct2/show/NCT00563173). Twelve patients with verified chronic HCV genotype 1 infections of a duration of >6 months were included in the study. Background data Entinostat of the patients, five females and seven males, with a mean age of 46 years (range 29�C60 years), have been given in Table 1. All were treatment naive and four had genotype 1b, seven had genotype 1a, and one had genotype 1 unspecified (Table 1).