Pseudotyping retrovirus like particles vaccine candidates with Hepatitis C virus envelope protein E2 requires the cellular expression of CD81
AMB EXPRESS
Authors: Soares, Hugo R.; Castro, Rute; Tomas, Helio A.; Carrondo, Manuel J. T.; Alves, Paula M.; Coroadinha, Ana S.
Abstract
Hepatitis C virus (HCV) infects 3% of world population being responsible for nearly half a million deaths annually urging the need for a prophylactic vaccine. Retrovirus like particles are commonly used scaffolds for antigens presentation being the core of diverse vaccine candidates. The immunogenicity of host proteins naturally incorporated in retrovirus was hypothesized to impact the performance of retrovirus based vaccines. In this work, the capacity of engineered retrovirus like particles devoided of host protein CD81 to display HCV envelope antigens was compared to non-engineered particles. A persistent inability of CD81 negative VLPs to incorporate HCV E2 protein as a result from the inefficient transport of HCV E2 to the plasma membrane, was observed. This work enabled the identification of a CD81-mediated transport of HCV E2 while stressing the importance of host proteins for the development of recombinant vaccines.
Hepatitis C Virus Seroprevalence in Mongolian Women Assessed by a Novel Multiplex Antibody Detection Assay
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Authors: Dondog, Bolormaa; Schnitzler, Paul; Michael, Kristina M.; Clifford, Gary; Franceschi, Silvia; Pawlita, Michael; Waterboer, Tim
Abstract
Background: Hepatitis C virus (HCV) infection causes hepatocellular carcinoma and is an important cause of mortality in both industrialized and developing countries. We developed a single-step high-throughput multiplex serology assay for HCV antibody detection and determined HCV prevalence in a highly endemic country. Methods: Five proteins (Core, NS3, NS4A, NS5A, NS5B) each from the three most common subtypes of HCV (1a, 1b, 2a) were recombinantly expressed and used as antigens in a multiplexed antibody detection assay. Multiplex HCV serology was validated with 432 reference sera whose HCV status was established by commercial ELISA, Western blot, and RNA assays. HCV antibodies were determined in 1,023 sera representative for the adult female population of Mongolia. Results: In reference sera, detection of HCV (mostly Core and NS3) antibodies by multiplex serology showed 100% sensitivity and 99.6% specificity, and was in very good agreement with the commercial diagnostic assays (kappa, 0.96; 95% confidence interval, 0.92-0.99). The role of antibodies to NS4 and NS5 remains to be evaluated. In Mongolia, overall HCV antibody prevalence was 18.9% (17.8% when age-standardized to the world population). HCV seroprevalence increased with age from 10% in women < 30 years to 32% in women >= 50 years, but was not related to sexual risk factors. Conclusions: The single-step high-throughput multiplex HCV serology assay performs similarly to conventional HCV antibody screening followed by secondary confirmation assays. A very high HCV seroprevalence was confirmed across all socio-economic groups in the female population of Mongolia. Impact: Multiplex HCV serology facilitates large seroepidemiologic studies of HCV infection. (C) 2015 AACR.