Hepatitis C Virus Antigens Research Articles

Exploring T-Cell Immunity to Hepatitis C Virus: Insights from Different Vaccine and Antigen Presentation Strategies.

The hepatitis C virus (HCV) is responsible for approximately 50 million infections worldwide. Effective drug treatments while available face access barriers, and vaccine development is hampered by viral hypervariability and immune evasion mechanisms. The CD4+ and CD8+ T-cell responses targeting HCV non-structural (NS) proteins have shown a role in the viral clearance. In this paper, we reviewed the studies exploring the relationship between HCV structural and NS proteins and their effects in contributing to the elicitation of an effective T-cell immune response. The use of different vaccine platforms, such as viral vectors and virus-like particles, underscores their versability and efficacy for vaccine development. Diverse HCV antigens demonstrated immunogenicity, eliciting a robust immune response, positioning them as promising vaccine candidates for protein/peptide-, DNA-, or RNA-based vaccines. Moreover, adjuvant selection plays a pivotal role in modulating the immune response. This review emphasizes the importance of HCV proteins and vaccination strategies in vaccine development. In particular, the NS proteins are the main focus, given their pivotal role in T-cell-mediated immunity and their sequence conservation, making them valuable vaccine targets.

Evaluating the performance of two different chemiluminescence analyzers systems in screening donors’ samples for HCV infection

BackgroundThe approved screening test for HCV infection among blood donors is the HCV antibody test. The diagnostic performances of the available immunoassays in the market that target different HCV antigens have not yet been thoroughly analyzed. Our study aimed to assess the diagnostic performances of two different chemiluminescence immunoassay (CLIA) assays.MethodsWe analyzed 1909 samples using two assay systems (COBAS e601 ROCHE® & Vitros 3600 ORTHO®) and evaluated the agreement of each with the gold standard method ELISA, as well as studying their diagnostic performances.ResultsThe Cohen’s Kappa statistics revealed excellent agreement between ELISA and both CLIA methods performed on Cobas e 601 ROCHE and Vitrous 3600 ORTHO (0.81 & 0.994 respectively). The sensitivities and positive predictive values were 95.05% and 73.85% for Cobas e 601 ROCHE, 100.00%, and 98.97% for Vitrous 3600 ORTHO, respectively.ConclusionsExcellent diagnostic performance was detected by both assays; however, Vitros 3600 ORTHO outperformed Cobas e 601 ROCHE in terms of sensitivity and specificity.

The red alga Porphyridium as a host for molecular farming: Efficient production of immunologically active hepatitis C virus glycoprotein

Microalgae are promising production platforms for the cost-effective production of recombinant proteins. We have recently established that the red alga Porphyridium purpureum provides superior transgene expression properties, due to the episomal maintenance of transformation vectors as multicopy plasmids in the nucleus. Here, we have explored the potential of Porphyridium to synthesize complex pharmaceutical proteins to high levels. Testing expression constructs for a candidate subunit vaccine against the hepatitis C virus (HCV), we show that the soluble HCV E2 glycoprotein can be produced in transgenic algal cultures to high levels. The antigen undergoes faithful posttranslational modification by N-glycosylation and is recognized by conformationally selective antibodies, suggesting that it adopts a proper antigenic conformation in the endoplasmic reticulum of red algal cells. We also report the experimental determination of the structure of the N-glycan moiety that is attached to glycosylated proteins in Porphyridium. Finally, we demonstrate the immunogenicity of the HCV antigen produced in red algae when administered by injection as pure protein or by feeding of algal biomass.

Immunological serum markers for hepatitis viral infections: HAV, HBV, HCV to advance of genetic engineering

Viral hepatitis is increasingly present in infections diagnosed around the world. Thousands of individuals are infected by these often-silent diseases that only manifest themselves when clinical signs are very advanced. Hepatitis A virus (HAV) is a vaccine-preventable liver infection. Recombinant vaccines had been applied with the advance of genetic engineering for HBV. New studies have investigated the improvement of the vaccine model of heterological antigens based on hepatitis B virus envelope protein containing HCV antigen as a chimeric vaccine. The aim of this study was to evaluate the detection rates of these viruses that induce liver damage and can progress to cancer depending on the associated epigenetic factors. Thus, between January 10, 2022, and March 31, 2023, about 2.750 samples were collected from 2.713 patients, of which 38.43% were for HCV and 30.25% for HAV research. For HBV, it had been analyzed about 2.222 samples from 1.660 patients, which females were more prevalent (60.60%) and males (39.39%). In all, eight biomarkers of the HBV were investigated and HBsAg marker was non-reactive in 44.01% of the total samples analyzed and 31,41% reactive for anti-HBs. HBV/HCV coinfected patients need more attention. New research about immunological serum markers should be better investigated to correlation the natural history of hepatitis viral infections and hepatocellular carcinoma (HCC) improve tumour genomic and epidemiological surveillance in clinical trials.

Seroprevalence of Human Immunodeficiency Virus, Hepatitis C Virus, and Hepatitis B Virus Among Blood Donors in Sidi Bel Abbes, West Algeria.

Introduction Blood transfusions can transmit various viruses. Among them, the most common are hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). These viruses can cause fatal and life-threatening diseases. Worldwide, many people are infected with these viruses. Blood safety has made majorprogress in recent years. Yet, blood-borne viruses continue to be a major concern for patients, physicians, and policymakers. The aim of this study was to assessthe prevalence of HIV, HBV, and HCV in blood donors. Methods A cross-sectional study was performed to assess HIV, HBV, and HCV seropositivity in blood donors. This research was carried out at the blood bank of Sidi Bel Abbes University Hospital. This was a retrospective study based on records of blood donors. All data of 10,386 donors were analyzed from January 2015 to December 2015. Biological screening was performed by enzyme-linked immunosorbent assay (ELISA) using antibodies and/or antigens. The combined HCV and HIV antigen and antibody ELISA test was utilized. To confirm the results, the blood bank and the virology laboratory used the same technique in duplicate. Results The overall seroprevalence of blood-borne viral infections (HIV, HBV, and HCV) in blood donors was 0.8%. The prevalence of HIV was found to be 0.1%, while the prevalence of HBV and HCV was 0.4%. Coinfection was rare with only one case of HBV with HIV.There was a significant difference in seroprevalence rates among blood donors compared to the general population. Significant variations were observed between the prevalence of this study and those conducted in West, East, Central, and South African countries but not with those of neighboringNorth African countries. The study found no association between seropositivity in blood donors and factors like age, gender, donor status, type of donation, or site. Besides, HIV, HBV, or HCV prevalence was not influenced by ABO and Rhesus blood group. Conclusion The study showed that blood donors in Algeria have a lower prevalence of blood-borne viral infections than the general population. The seropositivity rate of viral markers was similar throughout North African countries. This rate remained low compared to other African countries. Residual risk of infection persists. There is a need to increase blood safety for recipients. This report is the first comprehensive overview of blood-borne viruses among Algerian blood donors. There is a need for further nationwide studies to get a whole picture of the situation.

Expression of the Hepatitis C Virus core-NS3 Fusion Protein on the Surface of Bacterial Ghosts: Prospects for Vaccine Production.

Antigen presentation using bacterial surface display systems, on one hand, has the benefits of bacterial carriers, including low-cost production and ease of manipulation. On the other hand, the bacteria can help in stimulating the immune system as an adjuvant. For example, using bacterial surface display technology, we developed a hepatitis C virus (HCV) multiple antigens displaying bacteria's surface and then turned it into a bacterial ghost. The HCV core and NS3 proteins' conserved epitopes were cloned into the AIDA gene plasmid as an auto transporter. The recombinant plasmid was then transformed into Escherichia coli (E. coli) Bl21 (DE3). Recombinant bacteria were then turned into a bacterial ghost, an empty cell envelope. Whole-cell ELISA, flow cytometry, and Western blot techniques were used for monitoring the expression of proteins on the surface of bacteria. A fusion protein of HCV core-NS3-AIDA was successfully expressed on the E. coli Bl21 (DE3) surface and confirmed by western blotting, Enzyme-Linked Immunosorbent Assay (ELISA), and flow cytometry detection techniques. The presence of HCV antigens on non-pathogen bacteria surfaces holds promise for developing safe and cost-benefit-accessible vaccines with optimal intrinsic adjuvant effects and exposure of heterologous antigens to the immune system.

A CLINICAL MANIFESTATION OF HEPATITIS C AMONG THE POPULATION OF HYDERABAD, PAKISTAN

Hepatitis C is a noteworthy public health issue around the globe, resulting in liver-related problems. Almost 80% of HCV patients suffer from chronic circumstances and are likely to have liver ailments. Approximately 6% population of Pakistan is infected with HCV. In this study of 510 samples were collected from May 2022 to September 2022 from Hyderabad and adjacent areas. 291 out of 510 samples were affected by HCV. The collected samples were screened based on ELISA using recombinant HCV antigens. Biochemical and hematological factors were performed on HCV-infected patients. RBC, Hemoglobin, WBC, MCV, MCHC, and PLT were observed normally in all age groups. But WBC and PLT are high in the 10-20 age groups. Hematocrit and MCH were decreased as compared to normal levels. Bilirubin, SGPT, and Alkaline phosphate were high in some age groups but normal in other age groups. Albumin was found normal in all patients. These parameters were correlated to each other to know the causes and prevention of HCV.

Serum neutralization activity declines but memory B cells persist after cure of chronic hepatitis C

The increasing incidence of hepatitis C virus (HCV) infections underscores the need for an effective vaccine. Successful vaccines to other viruses generally depend on a long-lasting humoral response. However, data on the half-life of HCV-specific responses are lacking. Here we study archived sera and mononuclear cells that were prospectively collected up to 18 years after cure of chronic HCV infection to determine the role of HCV antigen in maintaining neutralizing antibody and B cell responses. We show that HCV-neutralizing activity decreases rapidly in potency and breadth after curative treatment. In contrast, HCV-specific memory B cells persist, and display a restored resting phenotype, normalized chemokine receptor expression and preserved ability to differentiate into antibody-secreting cells. The short half-life of HCV-neutralizing activity is consistent with a lack of long-lived plasma cells. The persistence of HCV-specific memory B cells and the reduced inflammation after cure provide an opportunity for vaccination to induce protective immunity against re-infection.

Comparing RT-qPCR and Hepatitis C Virus Antigen Detection Assay for Detecting Active Infection in Blood Donors in Fars Province, Iran

Background: Immunoassay is still used to detect hepatitis C virus (HCV) antibodies in donated blood in many developing countries. However, an immunoblotting confirmation test is needed to confirm positive results. Objectives: We compared the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of nucleic acid testing and HCV core antigen (HCVcAg) detection in the serum samples of blood donors with HCV antibodies to determine active infection. Methods: Overall, 90 serum samples from blood donors referred to Fars Blood Transfusion Organization, Iran during March 2017-March 2019 and initially tested for HCV antibodies were included in the study. Enzyme immunoassays were used to detect the HCV antigen and anti-HCV antibody. A commercial reverse transcription-polymerase chain reaction (RT-PCR) kit was used to quantify HCV RNA. The HCV genotypes were also determined by DNA sequencing. In order to compare the HCVcAg detection method with the RT-qPCR reference method, sensitivity, specificity, performance, PPV, and NPV were calculated. Results: Out of 90 serum samples, 73 were positive for anti-HCV antibody, and 17 sera were negative. The HCV RNA was detected in 60 (82%) of anti-HCV antibody-positive samples, whereas the HCVcAg test detected HCV antigen in 54 (74%) of the samples, indicating a significant correlation between the two assays (r = 0.86). The overall sensitivity and specificity for HCVcAg detection method were 93.85% [95% confidence interval (CI): 84.99 - 98.3%] and 100% (95% CI: 94.64 - 100%), respectively. Based on the statistical analysis, the accuracy of the antigen detection test was 94.83% (95% CI: 87.26 - 98.58%). Moreover, the agreement between HCV RNA detection using RT-qPCR and HCVcAg detection was 97.78% (kappa value: 0.94). Conclusions: The sensitivity and specificity of HCVcAg detection in blood donors were ideal compared to the RT-qPCR reference method. However, the method should be tested on more HCV antibody-positive and -negative samples. Furthermore, our study revealed a significant association between the number of RT-qPCR-positive cases and the cases diagnosed by the HCVcAg detection method for screening and detecting active HCV infection in blood donors.

VirA+EmiC project: Evaluating real-world effectiveness and sustainability of integrated routine opportunistic hepatitis B and C testing in a large urban emergency department.

Innovative testing approaches and care pathways are required to meet global hepatitis B virus (HBV) and hepatitis C virus (HCV) elimination goals. Routine blood‐borne virus (BBV) testing in emergency departments (EDs) in high‐prevalence areas is suggested by the European Centre for Disease Prevention and Control (ECDC) but there is limited evidence for this. Universal HIV testing in our ED according to UK guidance has been operational since 2015. We conducted a real‐world service evaluation of a modified electronic patient record (EPR) system to include opportunistic opt‐out HBV/reflex‐HCV tests for any routine blood test orders for ED attendees aged ≥16 years. Reactive laboratory results were communicated directly to specialist clinical teams. Our model for contacting patients requiring linkage to care (new diagnoses/known but disengaged) evolved from initially primarily hospital‐led to collaborating with regional health and community service networks. Over 11 months, 81,088 patients attended the ED; 36,865 (45.5%) had a blood test. Overall uptake for both HBV and HCV testing was 75%. Seroprevalence was 0.9% for hepatitis B surface antigen (HBsAg) and 0.9% for HCV antigen (HCV‐Ag). 79% of 140 successfully contacted HBsAg+patients required linkage to care, of which 87% engaged. 76% of 130 contactable HCV‐Ag+patients required linkage, 52% engaged. Our results demonstrate effectiveness and sustainability of universal ED EPR opt‐out HBV/HCV testing combined with comprehensive linkage to care pathways, allowing care provision particularly for marginalized at‐risk groups with limited healthcare access. The findings support the ECDC BBV testing guidance and may inform future UK hepatitis testing guidance.

An ultrasensitive electrochemical immunosensor for hepatitis C antibodies based on one-step-eletrosynthetized polypyrrole-graphene nanocomposite.

An ultrasensitive label-free electrochemical immunosensor was developed for hepatitis C antibodies (anti-HCV). Worldwide, it is estimated 71 million people have HCV infection in a chronic stage that may lead to cirrose and cancer. To achieve HCV elimination, health programs should include screening testing based on anti-HCV detection allowing the early-stage treatment. The immunosensor was based on a graphene oxide-polypyrrole (PPy–GO) film one-step electropolymerized on the electrode surface. Ultrasensitive anti-HCV detection was ensured by HCV antigen conjugated to biotin that was immobilized in a great amount on streptavidin-coated nanostructured surface. Analytical responses were obtained by anodic peaks from the square wave voltammetry in the presence of ferrocyanide/ferricyanide as a redox probe. This immunosensor exhibited a linear range from 2 to 14 ng mL−1 of anti-HCV and a limit of detection in the clinical range (1.63 ng mL−1). Furthermore, the immunosensor presented an efficient performance for the determination of anti-HCV in spiked serum samples, becoming this developed nanosensor as potential tools for early HCV diagnosis and screening.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10853-022-06992-5.

Performance Evaluation of In Vitro Screening and Diagnostic Kits for Hepatitis C Virus Infection.

AimA reliable kit with high sensitivity and specificity is indispensable for diagnosing hepatitis C virus (HCV) infection. Detection kits for anti-HCV antibodies (anti-HCV) are used for screening, and quantification kits for HCV RNA and HCV antigen (Ag) are used for the definite diagnosis of HCV infection or the evaluation of the pathological condition of and therapeutic effects in patients with chronic hepatitis C. Several kits are currently available for these purposes and are provided for clinical use in Japan. In this study, we aimed to evaluate the performance of these kits.MethodsWe used International Standards for HCV RNA and HCV Ag and a regional reference panel to evaluate the performance of thirteen anti-HCV, five HCV RNA, and two HCV Ag kits.ResultsAll specimens in the regional reference panel were diagnosed correctly by all anti-HCV kits, although the distributions of the quantified values varied, and the ratios of titer classification were not identical across kits. All HCV RNA kits quantified the International Standard with minimum deviation and diagnosed the specimens of the reference panel correctly. The quantified values of the International Standard by two HCV Ag kits were inconsistent. HCV Ag titers of some specimens were underestimated owing to the amino acid polymorphisms in comparison with HCV RNA titers.ConclusionsThe evaluation with International Standards and the regional reference panel was useful for assessing the quality of screening and diagnostic kits for HCV infection, and such quality control is essential for the clinical usage of these kits.

Performance of HCV Antigen Testing for the Diagnosis and Monitoring of Antiviral Treatment: A Systematic Review and Meta-Analysis.

Background and Aims Active hepatitis C virus (HCV) infection is based on the detection of HCV RNA that it is effective but presents high cost and the need to hire trained personnel. This systematic review and meta-analysis is aimed at evaluating the diagnostic accuracy of HCV Ag testing to identify HCV cases and to monitor antiviral treatment including DAA treatment. Methods The studies were identified through a search in PubMed, Lilacs, and Scopus from 1990 through March 31, 2020. Cohort, cross-sectional, and randomized controlled trials were included. Two independent reviewers extracted data and assessed quality using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Our primary outcome was to determine the accuracy of HCV Ag detection for the diagnosis, which we estimated using random-effects meta-analysis. Results Of 3,062 articles identified, 54 met our eligibility criteria. The studies described cohorts from 20 countries, including 14,286 individuals with chronic HCV individuals. Studies for ECLIA technology demonstrated highest quality compared to studies that used ELISA. The pooled sensitivity and specificity (95% CI) for HCV Ag detection of active HCV infection were 98.82% (95%CI = 98.04%; 99.30%) and 98.95% (95%CI = 97.84%; 99.49%), respectively. High concordance was found between HCV Ag testing and HCV RNA detection 89.7% and 95% to evaluate antiviral treatment. Conclusions According to our findings, HCV Ag testing could be useful to identify HCV active cases in low-resource areas. For antiviral treatment, HCV Ag testing will be useful at the end of treatment.

Occult Infection with Hepatitis C Virus: Looking for Clear-Cut Boundaries and Methodological Consensus.

The sustained virologic response and elimination of HCV is widely viewed as a true cure of chronic hepatitis C as it associates with amelioration of histological liver damage and improved clinical outcomes. Therefore, the existence and clinical burden of occult HCV infection (OCI) has been a controversial issue for many years. In this review, we summarize recently published data that adds new information on the molecular and clinical background of OCI and its epidemiological significance. We also identify and discuss the most important methodological pitfalls, which can be a source of inconsistency between studies. Data that have accumulated so far, strongly support the existence of extrahepatic HCV replication in individuals negative for serum HCV-RNA by conventional clinical tests. OCI emerges as a condition where the immune system is unable to fully resolve infection but it is continuously stimulated by low levels of HCV antigens, leading to progression of liver pathology and extrahepatic HCV-related complications. Moreover, the development of monitoring strategies or management guidelines for OCI is still hampered by the lack of clear definition and the confusion regarding its clinical significance. Careful study design and the introduction of uniform protocols for the detection of low-level HCV-RNA are crucial for obtaining reliable data on OCI.

Routine screening for hepatitis C in pregnancy is cost-effective in a large urban population in Ireland: a retrospective study.

To investigate whether risk factor-based screening in pregnancy is failing to identify women with hepatitis C virus (HCV) infection and to assess the cost-effectiveness of universal screening. Retrospective study and model-based economic evaluation. Two urban tertiary referral maternity units, currently using risk factor-based screening for HCV infection. Pregnant women who had been tested for hepatitis B, HIV but not HCV. Anonymised sera were tested for HCV antibody. Positive sera were tested for HCV antigen. A cost-effectiveness analysis of a change to universal screening was performed using a Markov model to simulate disease progression and Monte Carlo simulations for probabilistic sensitivity analysis. Presence of HCV antigen and cost per quality-adjusted life year (QALY). In all, 4655 samples were analysed. Twenty had HCV antibodies and five HCV antigen. This gives an active infection rate of 5/4655, or 0.11%, compared with a rate of 0.15% in the risk-factor group. This prevalence is 65% lower than a previous study in the same hospitals from 2001 to 2005. The calculated incremental cost-effectiveness ratio (ICER) for universal screening was €3,315 per QALY gained. This study showed that the prevalence of HCV infection in pregnant women in the Dublin region has declined by 65% over the past two decades. Risk factor-based screening misses a significant proportion of infections. A change to universal maternal screening for hepatitis C would be cost-effective in our population. Universal maternal screening for hepatitis C is cost-effective in this urban Irish population.

Population-level estimates of hepatitis C reinfection post scale-up of direct-acting antivirals among people who inject drugs

Background & AimsScale-up of highly effective direct-acting antivirals (DAAs) for HCV among people who inject drugs (PWID) in Scotland has led to a reduction in the prevalence of viraemia in this population. However, the extent of reinfection among those treated with DAAs remains uncertain. We estimated HCV reinfection rates among PWID in Scotland by treatment setting, pre- and post-introduction of DAAs, and the potential number of undiagnosed reinfections resulting from incomplete follow-up testing.MethodsThrough linkage of national clinical and laboratory HCV data, a retrospective cohort of PWID who commenced treatment between 2000-2018 and achieved a sustained virological response (SVR) were followed up for reinfection to December 2019. Reinfection was defined as a positive HCV antigen or RNA test.ResultsOf 5,686 SVRs among 5,592 PWID, 4,126 (73%) had an HCV RNA or antigen test post-SVR. Of those retested, we identified 361 reinfections (3.9/100 person-years [PY]). The reinfection rate increased from 1.5/100 PY among PWID treated in 2000-2009 to 8.8/100 PY in 2017-2018. The highest reinfection rates were observed among those treated in prison (14.3/100 PY) and community settings (9.5/100 PY). Among those treated in the DAA era (2015-2018), 68% were tested within the first year post-SVR but only 30% in the second year; while 169 reinfections were diagnosed in follow-up, an estimated 200 reinfections (54% of the estimated total) had gone undetected.ConclusionsHCV reinfection rates among PWID in Scotland have risen alongside the scale-up of DAAs and broadened access to treatment for those at highest risk, through delivery in community drug services. Promotion of HCV testing post-SVR among PWID is essential to ensure those reinfected are identified and retreated promptly.Lay summaryIncreased rates of hepatitis C reinfection in Scotland were observed following the rapid scale-up of highly effective direct-acting antiviral (DAA) treatments among people who inject drugs. This demonstrates that community-based treatment pathways are reaching high-risk groups, regarded vital in efforts to eliminate the virus. However, we estimate that less than half of reinfections have been detected in the DAA era because of inadequate levels of retesting beyond the first year following successful treatment. Sustained efforts that involve high coverage of harm reduction measures and high uptake of annual testing are required to ensure prompt diagnosis and treatment of those reinfected if the goals of elimination are to be met.

Role of hepatitis C virus core antigen assay in hepatitis C care in developing country

BackgroundThe World Health Organization (WHO) aims to achieve global hepatitis C elimination by 2030, defined as diagnosis of 90% of infected individuals and treating 80% of them. Current guidelines for the screening and diagnosis of hepatitis C infection denote using a relatively cheap screen with anti-hepatitis C virus (HCV) antibody immunoassay, followed by the much costlier molecular test for HCV RNA levels using polymerase chain reaction (PCR) assay to confirm active HCV infection. Simplification of the HCV evaluation algorithm to reduce the number of required tests could considerably expand the provision of HCV treatment especially in a developing country. This study investigates the performance of hepatitis C Core Antigen (HCV Ag) test by comparing HCV Ag results versus the results obtained with HCV ribonucleic acid (RNA) PCR which is considered the gold standard for the diagnosis of HCV infection.ResultsAmong the 109 anti-HCV positive sera, 96 were positive for both HCV Ag (> 3 fmol/L) and HCV RNA (> 15 IU/mL); 8 were negative for both tests, while the remaining 5 were positive for HCV RNA only. Considering the HCV RNA as gold standard; the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HCV Ag test were found to be 95.05%, 100%, 100%, and 61.54%, respectively. HCV genotype was performed for 59 patients. The most common HCV genotype was genotype 1 (72.9%). Genotype 2 (15.3%) and genotype 3 (11.9%) were detected in the others samples. A high level of correlation was seen between HCV RNA and HCV Ag (r = 0.958, p < 0.001). The correlation for the samples that were genotyped 1 was significant (r = 0.966, p < 0.001).ConclusionIn our study, it was found that there was strong correlation between HCV RNA levels and HCV Ag levels. So, it can be used for a one-step HCV antigen test to diagnose active HCV infection.

Reflex HCV RNA or antigen testing cost effective for HCV screening

Reflex HCV RNA or antigen testing cost effective for HCV screening

Interferon lambda 4 impairs hepatitis C viral antigen presentation and attenuates T cell responses

Genetic variants of the interferon lambda (IFNL) gene locus are strongly associated with spontaneous and IFN treatment-induced clearance of hepatitis C virus (HCV) infections. Individuals with the ancestral IFNL4-dG allele are not able to clear HCV in the acute phase and have more than a 90% probability to develop chronic hepatitis C (CHC). Paradoxically, the IFNL4-dG allele encodes a fully functional IFNλ4 protein with antiviral activity against HCV. Here we describe an effect of IFNλ4 on HCV antigen presentation. Only minor amounts of IFNλ4 are secreted, because the protein is largely retained in the endoplasmic reticulum (ER) where it induces ER stress. Stressed cells are significantly weaker activators of HCV specific CD8+ T cells than unstressed cells. This is not due to reduced MHC I surface presentation or extracellular IFNλ4 effects, since T cell responses are restored by exogenous loading of MHC with HCV antigens. Rather, IFNλ4 induced ER stress impairs HCV antigen processing and/or loading onto the MHC I complex. Our results provide a potential explanation for the IFNλ4–HCV paradox.

Structure-Based and Rational Design of a Hepatitis C Virus Vaccine.

A hepatitis C virus (HCV) vaccine is a critical yet unfulfilled step in addressing the global disease burden of HCV. While decades of research have led to numerous clinical and pre-clinical vaccine candidates, these efforts have been hindered by factors including HCV antigenic variability and immune evasion. Structure-based and rational vaccine design approaches have capitalized on insights regarding the immune response to HCV and the structures of antibody-bound envelope glycoproteins. Despite successes with other viruses, designing an immunogen based on HCV glycoproteins that can elicit broadly protective immunity against HCV infection is an ongoing challenge. Here, we describe HCV vaccine design approaches where immunogens were selected and optimized through analysis of available structures, identification of conserved epitopes targeted by neutralizing antibodies, or both. Several designs have elicited immune responses against HCV in vivo, revealing correlates of HCV antigen immunogenicity and breadth of induced responses. Recent studies have elucidated the functional, dynamic and immunological features of key regions of the viral envelope glycoproteins, which can inform next-generation immunogen design efforts. These insights and design strategies represent promising pathways to HCV vaccine development, which can be further informed by successful immunogen designs generated for other viruses.