The study protocol was registered at ClinicalTrials

The study protocol was registered at ClinicalTrials.gov under registration no.NCT00536627. stopping analogue treatment. Importantly, before cessation of treatment serum hepatitis B surface antigen (HBsAg) titers were significantly associated with DNA or HBsAg clearance. Therapeutic vaccination in CHB patients with persistent suppression of HBV replication led to the persistence of T-cell responses, but further improvements should be searched for to control infection after treatment discontinuation. == Introduction == With more than 350 million of chronic hepatitis B virus (HBV) carriers worldwide, HBV infection remains an important health problem. The ultimate goal of HBV therapy is to obtain a complete viral suppression with long-term nondetection of serum HBV Rabbit Polyclonal to Glucagon DNA and to cure the infection,i.e., to obtain clearance of serum hepatitis B surface antigen (HBsAg) and anti-HBs seroconversion. Antiviral drugs such as interferon (IFN)- and nucleos(t)ide analogues (NUC) efficiently suppress viral replication and reduce liver-related mortality. However, treatment with IFN- LB-100 has limited positive effects and numerous major side effects.1The persistence of covalently closed circular HBV DNA, the risk of viral resistance and the long-term duration of therapy are the main limits of NUC. An alternative approach to antiviral treatment is modulation of the immune response that is defective in patients with chronic infection.2As the adaptive and innate immune responses are known to be involved in viral clearance during acute self-limiting HBV infection,3,4therapeutic vaccination is a promising future strategy to control chronic viral infection. Since T-cell hyporesponsiveness is associated with high viral load, it has been suggested that reducing viral load before applying vaccine therapy could be a rational strategy to improve the immune response in HBV carriers.5In a preliminary phase Ib trial in lamivudine resistant patients, we have previously shown encouraging results with 5 injections of a recombinant DNA vaccine encoding two out of the three HBV envelope proteins. A restoration of NK cell functions and HBV-specific T-cell responses was observed, although this was transient.6,7Interestingly, an anti-HBe seroconversion occurred in the patients with the lowest viral load at the beginning of the trial, highlighting the importance of HBV DNA titers for successful immunotherapy. Analogues such as lamivudine and adefovir dipivoxyl have been shown to enhance T-cell responses concomitantly with a viral load decrease.8,9,10Based on these observations, a phase I/II, open, prospective, LB-100 multicenter trial clinical trial involving chronic HBV carriers with effective NUC treatments was designed (ClinicalTrials.govNCT00536627). Patients were LB-100 randomized to receive HBV envelope-expressing DNA injections or nothing and antiviral treatments were stopped in both groups 2 weeks after the last DNA injection. The primary endpoint of this trial was vaccine protection against the virological breakthrough that may occur during treatment with analogues and against reactivation after the end of analogue treatment. In this article, we report a substudy analyzing the efficacy of the DNA vaccine to induce an efficient immune response in HBeAg bad () individuals that were successfully treated by antivirals. We LB-100 showed that DNA vaccination allowed the maintenance of the number, the diversity and the features of envelope-specific T-cell reactions and that HBsAg titers account for an important determinant of serological and virological reactions. Nevertheless, the presence of an adaptive immune response was not able to prevent HBV reactivation in individuals after NUC discontinuation. == Results == == Ex lover vivoHBV-specific T-cell reactions in individuals == Seventy individuals with viral weight below 12 IU/ml were randomized to receive five injections of pCMV-S2S DNA (vaccine group) or nothing (control group) on week (W) 0 (baseline), W8, W16, W40, and W44. To avoid a potential effect of the HBeAg status on the immune response, only 31 individuals from.