1141 IMPACT OF LIVER BIOPSY FRAGMENT LENGTH AND LOCATION ON AUTOMATED QUANTITATIVE MEASURES OF FIBROSIS AND STEATOSIS

Abstract

responses that protect chimpanzees from chronic infection. Since pre-existing anti-vector immunity may limit vaccine efficacy we performed a phase-I clinical trial using adenoviral vectors found at low sero-prevalence to assess the safety and immunogenicity of this approach in humans. Methods: Replicative-defective human Ad6 and a novel simian AdCh3 vector that encode 1985 amino-acids derived from the NS3–5 region of a genotype-1b strain were administered (i.m.) in a double prime, heterologous boost strategy to 27 healthy volunteers. Volunteers were primed with two doses of the same Adenovirus vector 4-weeks apart in successive cohorts, at 3 vaccine doses (5×108vp, 5×109vp, 2.5×1010vp) and boosted 24 weeks later with the alternative vector at 2.5×1010vp. Immunogenicity was assessed by ex-vivo IFNg-ELISpot (using 6 peptide pools spanning the HCV immunogen), thymidine incorporation proliferation and ICS assays. Results: Both vectors were found to be highly immunogenic after a single vaccination. Following priming vaccinations with AdHu6 the average peak HCV specific ELISpot response was 1863 SFU/10 PBMC and with AdCh3 2186 SFU/10 PBMC at the higher vaccine dose (2.5×1010vp). All vaccinees responded to the highest vaccine dose of both vectors and at this dose HCV specific responses were always multi-specific with 7/10 individuals responding to 4 or more peptide pools. Proliferative responses to multiple NS proteins were readily detected. Preferential T-cell boosting was observed with the AdHu6/AdCh3 prime/boost regimen; here the average peak postboost T-cell response was 1080 SFU/10 PBMC. ICS showed that both polyfunctional CD4+ and CD8+ HCV specific T-cell responses are induced. Importantly T-cell responses were maintained to the last time point assessed-52 weeks post prime. Vaccination was very well tolerated with mild/moderate local and systemic reactions and no serious adverse advents. Conclusions: We have generated a novel T-cell vaccine based on adenovirus vectors from rare serotypes, that is safe in man, induces polyfunctional CD4+ and CD8+ T cells, is highly immunogenic against multiple antigenic targets, and which is durable to at least a year.