Neutralizing antibodies to interferon alfa arising during peginterferon therapy of chronic hepatitis B in children and adults: Results from the HBRN Trials.

Background Aims: Pegylated interferon-α (PegIFNα) is of limited utility during immunotolerant or immune active phases of chronic hepatitis B infection but is being explored as part of new cure regimens. Low/absent levels of IFNα found in some patients receiving treatment are associated with limited/no virological responses. The study aimed to determine if sera from participants inhibit IFNα activity and/or contain therapy-induced anti-IFNα antibodies.

Polyvalent immunization elicits a synergistic broadly neutralizing immune response to hypervariable region 1 variants of hepatitis C virus.

A hepatitis C virus (HCV) vaccine is urgently needed. Vaccine development has been hindered by HCV's genetic diversity, particularly within the immunodominant hypervariable region 1 (HVR1). Here, we developed a strategy to elicit broadly neutralizing antibodies to HVR1, which had previously been considered infeasible.

A Novel Information-Theory-Based Genetic Distance That Approximates Phenotypic Differences.

Application of genetic distances to measure phenotypic relatedness is a challenging task, reflecting the complex relationship between genotype and phenotype. Accurate assessment of proximity among sequences with different phenotypic traits depends on how strongly the chosen distance is associated with structural and functional properties. In this study, we present a new distance measure Mutual Information and Entropy H (MIH) for categorical data such as nucleotide or amino acid sequences.

Impacting Management of Chronic Kidney Disease Through Primary Care Practice Audits: A Quality Improvement Study.

Background: Risk prediction tools are important in chronic disease management, but their implementation into clinical workflow is often limited by lack of electronic health record (EHR)-linked solutions.

Objective: To implement the Khure Health (KH) clinical decision support platform with an artificial intelligence (AI)-enabled algorithm for chronic kidney disease (CKD) risk detection in 201 primary care provider practices across Ontario.

Design: Multi-practice quality improvement study.

HepG2-NTCP Subclones Exhibiting High Susceptibility to Hepatitis B Virus Infection.

HepG2 cells reconstituted with Hepatitis B virus (HBV) entry receptor sodium taurocholate co-transporting polypeptide (NTCP) are widely used as a convenient in vitro cell culture infection model for HBV replication studies. As such, it is pertinent that HBV infectivity is maintained at steady-state levels for an accurate interpretation of in vitro data. However, variations in the HBV infection efficiency due to imbalanced NTCP expression levels in the HepG2 cell line may affect experimental results.

Implications of viral transmitted/founder (T/F) dynamics on vaccine development.

Viral infection typically originates from a limited number of virions known as transmitted/founder (T/F) viruses. Studies of cross-species transmission, and intra-species transmission of antigenically variable viruses, indicates T/F variants may express distinct, transmissibility enhancing phenotypes. However, with evidence that transmissibility is associated with not only intrinsic virological features, such as virion composition, but also extrinsic factors, such as viral population structure, the challenge of resolving T/F signatures that can be targeted by rational vaccine or antiviral design is substantial.

Antigenic Variability.

Protective vaccines for hypervariable pathogens are urgently needed. It has been proposed that amputating highly variable epitopes from vaccine antigens would induce the production of broadly protective antibodies targeting conserved epitopes. However, so far, these approaches have failed, partially because conserved epitopes are occluded and partially because co-localizing patterns of immunodominance and antigenic variability render variable epitopes the primary target for antibodies in natural infection.

Role of HVR1 sequence similarity in the cross-genotypic neutralization of HCV.

Despite available treatments, a prophylactic HCV vaccine is needed to achieve elimination targets. HCV vaccine development has faltered largely because the extreme diversity of the virus limits the protective breadth of vaccine elicited antibodies. It is believed that the principle neutralizing epitope in natural infection, HVR1, which is the most variable epitope in HCV, mediates humoral immune escape.

A bivalent HCV peptide vaccine elicits pan-genotypic neutralizing antibodies in mice.

Vaccine development for antigenically variable pathogens has faltered because extreme genetic diversity precludes induction of broadly neutralizing antibodies (nAB) with classical vaccines. Here, using the most variable epitope of any known human pathogen (HVR1 of HCV), we describe a novel approach capable of eliciting broadly neutralizing antibodies targeting highly variable epitopes. Our proof-of-concept vaccine elicited pan-genotypic nAB against HCV variants differing from the immunogen sequences by more than 70% at the amino acid level.