Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe

Background: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. Methods: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. Results: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by ana

The Netherlands Is on Track to Meet the World Health Organization Hepatitis C Elimination Targets by 2030

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Kinetics of meningococcal serogroup C specific functional antibody levels up to 15 years after a single immunization with a meningococcal serogroup C conjugate vaccine during adolescence

BACKGROUND: Adolescent vaccination is now considered the key factor to offer direct protection against meningococcal disease but also to reduce carriage and transmission and in this way establish herd protection. This study estimated age-dependent patterns in functional meningococcal serogroup C (MenC) antibody kinetics after primary MenC conjugate (MenCC) vaccination in adolescents. METHODS: Serum samples (n=1676) were drawn between 2006-2011 from individuals aged 9-18 years at time of primary MenCC vaccination in 2002. Functional antibody levels were measured with serum bactericidal assay using rabbit complement (SBA). RESULTS: SBA titers gradually declined with time. Up to nine years after primary vaccination SBA titers were estimated to be higher in individuals aged 13-18 years at priming compared to those aged 9-10 years at priming. Based on a linear mixed model the higher functional antibody level with age seem to be due to the achievement of higher peak levels upon vaccination, rather than lower rates of decline. It is estimated that 35-50% of the individuals who received a single primary MenCC vaccination at an age between 9-18 years in 2002 will still have sufficient protective antibody levels fifteen years later. CONCLUSION: Using a linear mixed model based on cohort data with a single dated serum sample per person we were able to estimate the level of protection against MenC up to 15 years after a single vaccination. The current study shows that analysis of antibody kinetics can be done using cross-sectional serology data, and is therefore relevant for future serosurveillance studies

Effects of Prophylactic and Therapeutic Paracetamol Treatment during Vaccination on Hepatitis B Antibody Levels in Adults: Two Open-Label, Randomized Controlled Trials

Worldwide, paracetamol is administered as a remedy for complaints that occur after vaccination. Recently published results indicate that paracetamol inhibits the vaccination response in infants when given prior to vaccination. The goal of this study was to establish whether paracetamol exerts similar effects in young adults. In addition, the effect of timing of paracetamol intake was investigated. In two randomized, controlled, open-label studies 496 healthy young adults were randomly assigned to three groups. The study groups received paracetamol for 24 hours starting at the time of (prophylactic use) - or 6 hours after (therapeutic use) the primary (0 month) and first booster (1 month) hepatitis B vaccination. The control group received no paracetamol. None of the participants used paracetamol around the second booster (6 months) vaccination. Anti-HBs levels were measured prior to and one month after the second booster vaccination on ADVIA Centaur XP. One month after the second booster vaccination, the anti-HBs level in the prophylactic paracetamol group was significantly lower (p = 0.048) than the level in the control group (4257 mIU/mL vs. 5768 mIU/mL). The anti-HBs level in the therapeutic paracetamol group (4958 mIU/mL) was not different (p = 0.34) from the level in the control group. Only prophylactic paracetamol treatment, and not therapeutic treatment, during vaccination has a negative influence on the antibody concentration after hepatitis B vaccination in adults. These findings prompt to consider therapeutic instead of prophylactic treatment to ensure maximal vaccination efficacy and retain the possibility to treat pain and fever after vaccination.Controlled-Trials.com ISRCTN03576945