Core Antigen Of Hepatitis Research Articles

Toward a SARS-CoV-2 VLP Vaccine: HBc/G as a Carrier for SARS-CoV-2 Spike RBM and Nucleocapsid Protein-Derived Peptides.

Virus-like particles (VLPs) offer an attractive possibility for the development of vaccines. Recombinant core antigen (HBc) of Hepatitis B virus (HBV) was expressed in different systems, and the E. coli expression system was shown to be effective for the production of HBc VLPs. Here, we used HBc of the HBV genotype G (HBc/G) as a technologically promising VLP carrier for the presentation of spike RBM and nucleocapsid protein-derived peptides of the SARS-CoV-2 Delta variant for subsequent immunological evaluations of obtained fusion proteins. The major immunodominant region (MIR) of the HBc/G protein was modified through the insertion of a receptor binding motif (RBM) from the S protein or B-cell epitope-containing peptide from the N protein. The C-terminus of the two truncated HBc/G proteins was used for the insertion of a group of five cytotoxic T lymphocyte (CTL) epitopes from the N protein. After expression in E. coli, the MIR-derived proteins were found to be insoluble and were recovered through step-wise solubilization with urea, followed by refolding. Despite the lack of correct VLPs, the chimeric proteins induced high levels of antibodies in BALB/c mice. These antibodies specifically recognized either eukaryotically expressed hRBD or bacterially expressed N protein (2-220) of SARS-CoV-2. CTL-epitope-containing proteins were purified as VLPs. The production of cytokines was analyzed through flow cytometry after stimulation of T-cells with target CTL peptides. Only a protein with a deleted polyarginine (PA) domain was able to induce the specific activation of T-cells. At the same time, the T-cell response against the carrier HBc/G protein was detected for both proteins. The neutralization of SARS-CoV-2 pseudotyped murine retrovirus with anti-HBc/G-RBM sera was found to be low.

The Study of Performance of a Nanoribbon Biosensor, Sensitized with Aptamers and Antibodies, upon Detection of Core Antigen of Hepatitis C Virus.

The development of highly sensitive diagnostic systems for the early revelation of diseases in humans is one of the most important tasks of modern biomedical research, and the detection of the core antigen of the hepatitis C virus (HCVcoreAg)-a protein marker of the hepatitis C virus-is just the case. Our study is aimed at testing the performance of the nanoribbon biosensor in the case of the use of two different types of molecular probes: the antibodies and the aptamers against HCVcoreAg. The nanoribbon sensor chips employed are based on "silicon-on-insulator structures" (SOI-NR). Two different HCVcoreAg preparations are tested: recombinant β-galactosidase-conjugated HCVcoreAg ("Virogen", Watertown, MA, USA) and recombinant HCVcoreAg ("Vector-Best", Novosibirsk, Russia). Upon the detection of either type of antigen preparation, the lowest concentration of the antigen detectable in buffer with pH 5.1 was found to be approximately equal, amounting to ~10-15 M. This value was similar upon the use of either type of molecular probes.

SAT-162 - The different immune response of B cells specific for hepatitis B virus core and envelope antigen in chronic hepatitis B patients with pegylated interferon-alpha treatment

SAT-162 - The different immune response of B cells specific for hepatitis B virus core and envelope antigen in chronic hepatitis B patients with pegylated interferon-alpha treatment

Immune Status for Hepatitis B and Risk for Occupational Exposure Virus Among Italian Nurses

Background: Healthcare workers (HCWs) are considered at higher risk for hepatitis B virus infection compared to the general population, due to their potential contact with blood or body fluids and possible needle stick injuries. In turn, infected HCWs may be a risk for patients. Hepatitis B vaccination programs represent a strategic approach to control the infection. Objectives: In this study, we aimed to evaluate the serological status of HCWs employed at the teaching hospital of Rome Tor Vergata and their risk of occupational injuries after the adoption of directive 2010/32/EU. Methods: Medical records of 539 HCWs were evaluated during their occupational medical examination at the Tor Vergata teaching hospital (PTV). All subjects were screened for specific viral markers: Hepatitis B surface antibodies (anti-HBs IgG), antibodies to hepatitis core antigen (anti-HBc IgG), and hepatitis B surface antigen (HBsAg). Data regarding needlestick injuries were collected by the prevention service team during the same year. Results: In this sample population, we found five subjects (0.9%) positive to the HBsAg, and most of them (four) were born in foreign countries. Moreover, seven subjects (1.3% of our population) were HBsAg-positive and anti-HBc-positive. A protective anti-HBs titer was found in 462 out of 527 (85.7%) subjects. The risk of being serologically unprotected was higher in males and subjects aged 40 years or older. The nurses were more protected than other healthcare professionals considering the anti-hepatitis B surface antibody titer. In 2018, 16 needlestick injuries were reported among our population of HCWs, with a global risk of 2.9% per year. Conclusions: Although hepatitis B virus (HBV) infection rate among HCWs was similar to that of the general population, the risk of HBV transmission in HCWs was likely to be high due to suboptimal vaccination coverage.

Immune Status for Hepatitis B and Risk for Occupational Exposure Virus Among Italian Nurses

Background: Healthcare workers (HCWs) are considered at higher risk for hepatitis B virus infection compared to the general population, due to their potential contact with blood or body fluids and possible needle stick injuries. In turn, infected HCWs may be a risk for patients. Hepatitis B vaccination programs represent a strategic approach to control the infection. Objectives: In this study, we aimed to evaluate the serological status of HCWs employed at the teaching hospital of Rome Tor Vergata and their risk of occupational injuries after the adoption of directive 2010/32/EU. Methods: Medical records of 539 HCWs were evaluated during their occupational medical examination at the Tor Vergata teaching hospital (PTV). All subjects were screened for specific viral markers: Hepatitis B surface antibodies (anti-HBs IgG), antibodies to hepatitis core antigen (anti-HBc IgG), and hepatitis B surface antigen (HBsAg). Data regarding needlestick injuries were collected by the prevention service team during the same year. Results: In this sample population, we found five subjects (0.9%) positive to the HBsAg, and most of them (four) were born in foreign countries. Moreover, seven subjects (1.3% of our population) were HBsAg-positive and anti-HBc-positive. A protective anti-HBs titer was found in 462 out of 527 (85.7%) subjects. The risk of being serologically unprotected was higher in males and subjects aged 40 years or older. The nurses were more protected than other healthcare professionals considering the anti-hepatitis B surface antibody titer. In 2018, 16 needlestick injuries were reported among our population of HCWs, with a global risk of 2.9% per year. Conclusions: Although hepatitis B virus (HBV) infection rate among HCWs was similar to that of the general population, the risk of HBV transmission in HCWs was likely to be high due to suboptimal vaccination coverage.

Carriage of Hepatitis B Virus and Risk Factors among Health Care Workers in Ogun State

Background: Health-care workers (HCWs) are often exposed to potentially infectious body fluids-carrying Hepatitis B virus (HBV) from their workplaces. Typically, most asymptomatic HBV carriers-status may remain unnoticed for decades, despite a few percentages of them with vaccination history. In this study, we aimed at investigating asymptomatic carriage of HBV and its associated risk factors among co-health workers ultimately impacting on patients. Methods: Venous blood samples and demographic data were obtained from a cross sectional survey of HCWs categories working in OOUTH, a referral teaching hospital and other selected health facilities in Ogun state. Immuno-chromatographic discs and Enzyme Linked Immuno-Sorbent assay (ELISA) techniques were adopted for the determination and confirmation of the presence of HBsAg, anti-HBs and total anti-HBc in sera. A structured questionnaire was used for obtaining demographic data which were analyzed by regression analytical technique. Results: About 11.44% (43) of the 376 healthcare workers (HCWs), were infected with HBV. The serological marker of viral particles identified in this positive study population included Hepatitis B envelope antigen (53.49%), Hepatitis Core antigen (13.15%), Hepatitis B surface antibodies (3.99%); and Hepatitis B core antibodies (0.80%). A significant association existed between risk factors such as recapping of used needles and carriage of HBV among the HCWs (p-value =0.017). Conclusion: The carriage rate (11.44%) of HBV among HCWs in Ogun state referral health facilities as against the 8% set standard by W.H.O. in 2009, depict the associated risk factors of asymptomatic carriage, pathogenesis and dissemination in and outside of the health facilities.

Efficient Production of Chimeric Hepatitis B Virus-Like Particles Bearing an Epitope of Hepatitis E Virus Capsid by Transient Expression in Nicotiana benthamiana.

The core antigen of hepatitis B virus (HBcAg) is capable of self-assembly into virus-like particles (VLPs) when expressed in a number of heterologous systems. Such VLPs are potential carriers of foreign antigenic sequences for vaccine design. In this study, we evaluated the production of chimeric HBcAg VLPs presenting a foreign epitope on their surface, the 551–607 amino acids (aa) immunological epitope of the ORF2 capsid protein of hepatitis E virus. A chimeric construct was made by the insertion of 56 aa into the immunodominant loop of the HBcAg. The sequences encoding the chimera were inserted into the pEAQ-HT vector and infiltrated into Nicotiana benthamiana leaves. The plant-expressed chimeric HBcHEV ORF2 551–607 protein was recognized by an anti-HBcAg mAb and anti-HEV IgG positive swine serum. Electron microscopy showed that plant-produced chimeric protein spontaneously assembled into “knobbly” ~34 nm diameter VLPs. This study shows that HBcAg is a promising carrier platform for the neutralizing epitopes of hepatitis E virus (HEV) and the chimeric HBcAg/HEV VLPs could be a candidate for a bivalent vaccine.

Nanowire Aptamer-Sensitized Biosensor Chips with Gas Plasma-Treated Surface for the Detection of Hepatitis C Virus Core Antigen

Herein, we have demonstrated highly sensitive real-time biospecific detection of a protein marker of hepatitis C—the core antigen of hepatitis C virus (HCVcoreAg)—using a nanowire (NW) biosensor. The primary element of the NW-biosensor is a chip with p-type conductance, bearing silicon-on-insulator (SOI) nanowire structures on its surface. The nanowire structures are fabricated by gas-plasma treatment and electron beam lithography. The detection specificity was provided by sensitization of the sensor surface with aptamers against HCVcoreAg. The influence of buffer pH on the sensor response signal was studied. The effect of reverse polarity of the biosensor response signal with change from the acidic buffer pH to the neutral one was found. The lowest detectable HCVcoreAg concentration was determined to be 2.0 × 10−15 M in both acidic (pH 5.1) and neutral (pH 7.4) buffer solution. The proposed aptamer-sensitized sensor was also successfully applied to detect HCVcoreAg in serum samples of hepatitis C patients.

Zika Virus-Like Particle (VLP) vaccine displaying Envelope (E) protein CD loop antigen elicits protective and specific immune response in a murine model

Zika virus (ZIKV) is a mosquito-borne flavivirus associated with Congenital Zika Syndrome (CZS), reflecting a wide range of congenital abnormalities in fetuses and infants infected with ZIKV before birth. ZIKV infections have also been associated with the neurological autoimmune disorder known as Guillian-Barré syndrome (GBS). To date, no vaccines or antiviral strategies are licensed for ZIKV. We used rational design to develop a novel ZIKV vaccine candidate using a Woodchuck Hepatitis core Antigen (WHcAg) Virus-Like Particle (VLP) scaffold for displaying selected antigens from the ZIKV Envelope (E) protein.A Zika-VLP vaccine candidate containing the CD Loop sub-structural domain from ZIKV E protein Domain III (WHcAg CD Loop) elicited a strong immune response in a murine model. Analysis of serum immunoglobulins demonstrated induction of both Th1- and Th2- mediated immune response. No cross-reacting antibodies were detected between Zika, dengue and yellow fever virus, demonstrating a high level of specificity for the ZIKV CD Loop antigen. Immunization with the WHcAg CD Loop vaccine candidate demonstrated immunoprotection in a murine model of ZIKV infection, stimulating protective antibodies associated with antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities. The WHcAg CD Loop candidate may represent a safer vaccine for preventing antibody dependent enhancement (ADE).

The relationship between viral response to Peg-IFNα-2a and the expression intensity of Hepatitis B core antigen in chronic hepatitis B patients

The relationship between viral response to Peg-IFNα-2a and the expression intensity of Hepatitis B core antigen in chronic hepatitis B patients

Designing a therapeutic hepatitis B vaccine to circumvent immune tolerance

ABSTRACTAn effective prophylactic hepatitis B virus (HBV) vaccine has long been available but is ineffective for chronic infection. The primary cause of chronic hepatitis B (CHB) and greatest impediment for a therapeutic vaccine is the direct and indirect effects of immune tolerance to HBV antigens. The resulting defective CD4+/CD8+ T cell response, poor cytokine production, insufficient neutralizing antibody (nAb) and poor response to HBsAg vaccination characterize CHB infection. The objective of this study was to develop virus-like-particles (VLPs) that elicit nAb to prevent viral spread and prime CD4+/CD8+ T cells to eradicate intracellular HBV. Eight neutralizing B cell epitopes from the envelope PreS1 region were consolidated onto a species-variant of the HBV core protein, the woodchuck hepatitis core antigen (WHcAg). PreS1-specific B cell epitopes were chosen because of preferential expression on HBV virions. Because WHcAg and HBcAg are not crossreactive at the B cell level and only partially cross-reactive at the CD4+/CD8+ T cell level, CD4+ T cells specific for WHcAg-unique T cell sites can provide cognate T-B cell help for anti-PreS1 Ab production that is not curtailed by immune tolerance. Immunization of immune tolerant HBV transgenic (Tg) mice with PreS1-WHc VLPs elicited levels of high titer anti-PreS1 nAbs equivalent to wildtype mice. Passive transfer of PreS1 nAbs into human-liver chimeric mice prevented acute infection and cleared serum HBV from mice previously infected with HBV in a model of CHB. At the T cell level, PreS1-WHc VLPs and hybrid WHcAg/HBcAg DNA immunogens elicited HBcAg-specific CD4+ Th and CD8+ CTL responses.

Maximizing anti-HBs seroresponsiveness inkidney transplant waitlist patients: A tertiary-center perspective .

Patients on dialysis are at risk of hepatitis B virus (HBV) infection, and antibodies against the hepatitis B surface antigen (anti-HBs) ≥ 10 IU/L are required. However, a high percentages of HBV vaccine nonresponders have been reported. We aimed to determine the optimal HBV vaccination protocol. Kidney transplant waitlisted patients were followed for 12 months and categorized into two groups. Group A included patients with sustained anti-HBs ≥ 10 IU/L who did not require vaccination. Group B consisted of patients with anti-HBs < 10 IU/L who were treated with a course of 4 double-dose HBV vaccinations. Without seroconversion after the first course, a second course was initiated. A third course, coadministered with the tetanus-diphtheria (Td) vaccine, was performed upon failure of the second course. A total of 266 patients were included, 140 were categorized into group A and 126 into group B. Higher serum phosphorus, hemoglobin, and antibodies against the hepatitis core antigen (anti-HBc) were associated with sustaining anti-HBs ≥10IU/L without vaccination. Diabetes mellitus (DM) was associated with the need for vaccination. For group B, 107 patients required 1 course of vaccination, 15 patients required 2 courses, and 4 patients required the third course with Td vaccine coadministration. Long dialysis vintage and low hemoglobin level were associated with seroconversion failure after the first course. Serum phosphorus, hemoglobin, DM, anti-HBc, and dialysis vintage were associated with the anti-HBs seroresponsiveness and sustainability. Our 3-course of 4 double-dose HBV vaccines regimen (with Td vaccine in the final course) conferred immunity to all patients.

IgG1 and IgG4 antibodies against Core and NS3 antigens of hepatitis C virus.

IgG subclasses involved in the immune response to hepatitis C virus (HCV) antigens have been rarely studied. We investigated the immune response mediated by IgG1 and IgG4 antibodies against the recombinant core and NS3 antigens in patients with chronic hepatitis C. Sixty patients infected with HCV genotype 1 without antiviral treatment and 60 healthy subjects participated in the study. Serum levels of alanine aminotransferase, HCV viremia, and the presence of cryoglobulinemia and liver fibrosis were determined. We investigated the serum IgG1 and IgG4 antibodies against recombinant HCV core and NS3 non-structural protein antigens using amplified indirect ELISA. Anti-core and anti-NS3 IgG1 antibodies were detected in 33/60 (55%) and 46/60 (77%) patients, respectively, whereas only two healthy control samples reacted with an antigen (NS3). Anti-core IgG4 antibodies were not detected in either group, while 30/60 (50%) patients had anti-NS3 IgG4 antibodies. Even though there were higher levels of anti-NS3 IgG4 antibodies in patients with low viremia (< 8 × 105 IU/mL), IgG1 and IgG4 antibody levels did not correlate with ALT levels, the presence of cryoglobulinemia, or degree of hepatic fibrosis. High production of anti-core and anti-NS3 IgG1 antibodies was observed in chronic hepatitis C patients. In contrast, IgG4 antibodies seemed to only be produced against the NS3 non-structural antigen and appeared to be involved in viremia control. IgG1 antibodies against structural and non-structural antigens can be detected in chronic hepatitis C, while IgG4 antibodies seem to be selectively stimulated by non-structural HCV proteins, such as the NS3 antigen.

Ultrasensitive nanowire-based detection of HCVcoreAg in the serum using a microwave generator

The detection of a hepatitis C protein marker – core antigen of hepatitis C virus (HCVcoreAg) with a nanowire field-effect transistor biosensor, coupled with a microwave generator, has been studied.

A glassy carbon immunoelectrode modified with vanadium oxide nanobelts for ultrasensitive voltammetric determination of the core antigen of hepatitis C virus

The authors describe a voltammetric immunoassay for the hepatitis C virus core antigen. It is based on the use of vanadium oxide nanobelts that were used to modify a glassy carbon electrode (GCE). The nanobelts have a large specific surface area that can be heavily loaded with antibody against the hepatitis C virus core antigen. Following blocking with BSA and by using riboflavin as an electrochemical probe, the immuno GCE (best operated at a working voltage of −0.45 V vs. Ag/AgCl) has a linear response that covers the 10 fg·mL−1 to 100 ng·mL−1 core antigen concentration range and a limit of detection as low as 1.3 fg mL−1. Compared to the other redox probes, riboflavin is superior because it is oxidized in the negative potential range, where the number of interfering species for riboflavin is small. The method was successfully applied to the determination of hepatitis C virus core antigen in spiked serum. In our perception, the use of a V2O5 nanobelt film as a support for bioreceptors has a wide scope in that in that it may be extended to immunoassays for various other diagnostically significant analytes.

TiO2 nanoparticles doped with Celestine Blue as a label in a sandwich immunoassay for the hepatitis C virus core antigen using a screen printed electrode

The authors describe an electrochemical immunoassay for the core antigen of hepatitis C virus (HCV). The method is based on the use of a screen-printed carbon electrode (SPCE) that was modified with a Nafion@TiO2 nanocomposite and loaded with secondary antibody (Ab2) to entrap Celestine Blue (CB). The material has architecture of the type CB/Ab2/Nafion@TiO2. A nanocomposite consisting of graphene, ionic liquid and fullerene was deposited on the SPCE first, and rhodium nanoparticles (RhNPs) were then deposited on the surface of modified electrode in order to immobilize primary antibody (Ab1). The antigen and CB/Ab2/Nafion@TiO2 were conjugated one by one to form a sandwich-type immunocomplex. The signal was obtained by differential pulse voltammetry whose intensity is related to the concentration of the antigen. The assay, if operated at a working voltage of typically 0.35 V (vs. Ag/AgCl) has a response that is linear in the 0.1 to 250 pg⋅mL−1 HCV core antigen concentration range, and the limit of detection is as low as 25 fg⋅mL−1. The assay was applied to the determination of the HCV core antigen in spiked human serum samples. In our perception, the method represents a promising platform for the detection of various antigens if appropriate antibodies are available.

INVESTIGATION OF THE SIGNIFICANCE OF DETECTION OF THE NUCLEOCAPSID ANTIGEN OF THE HEPATITIS C VIRUS IN CHILDREN WITH CHRONIC HEPATITIS C

The aim of this study was to investigate the clinical and diagnostic significance of the detection of core-antigen of hepatitis C virus (HCV) in children with chronic hepatitis C (CHC). Sera of 101 patients and 24 non-infected participants were analyzed. Core-antigen was determined by chemiluminescent method using «ARCHITECT HCV Ag» (Abbott, USA). HCV RNA was detected by highly sensitive OT-PCA. The presence of liver fibrosis was established by non-invasive methods. Antibody to core-antigen was detected by ELISA using commercial test-systems. A correlation was found between concentration of core-antigen and HCV RNA, viral subtypes, ALT level, and presence of liver fibrosis. High sensitivity and specificity of the chemiluminescent method for the detection of core antigen in children with CHC was shown. For the first time three ranges of core-antigen concentrations were proposed.

Bioinformatic Identification of Rare Codon Clusters (RCCs) in HBV Genome and Evaluation of RCCs in Proteins Structure of Hepatitis B Virus.

BackgroundHepatitis B virus (HBV) as an infectious disease that has nine genotypes (A - I) and a ‘putative’ genotype J.ObjectivesThe aim of this study was to identify the rare codon clusters (RCC) in the HBV genome and to evaluate these RCCs in the HBV proteins structure.MethodsFor detection of protein family accession numbers (Pfam) in HBV proteins, the UniProt database and Pfam search tool were used. Protein family accession numbers is a comprehensive and accurate collection of protein domains and families. It contains annotation of each family in the form of textual descriptions, links to other resources and literature references. Genome projects have used Pfam extensively for large-scale functional annotation of genomic data; Pfam database is a large collection of protein families, each represented by multiple sequence alignments and hidden Markov models (HMMs). The Pfam search tools are databases that identify Pfam of proteins. These Pfam IDs were analyzed in Sherlocc program and the location of RCCs in HBV genome and proteins were detected and reported as translated EMBL nucleotide sequence data library (TrEMBL) entries. The TrEMBL is a computer-annotated supplement of SWISS-PROT that contains all the translations of European molecular biology laboratory (EMBL) nucleotide sequence entries not yet integrated in SWISS-PROT. Furthermore, the structures of TrEMBL entries proteins were studied in the PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software®.ResultsThe Pfam search tool found nine protein families in three frames. Results of Pfams studies in the Sherlocc program showed that this program has not identified RCCs in the external core antigen (PF08290) and truncated HBeAg gene (PF08290) of HBV. By contrast, the RCCs were identified in gene of hepatitis core antigen (PF00906 and the residues 224 - 234 and 251 - 255), large envelope protein S (PF00695 and the residues 53-56 and 70 - 84), X protein (PF00739 and the residues 10 - 24, 29 - 83, 95 - 99. 122 - 129, 139 - 143), DNA polymerase (viral) N-terminal domain (PF00242 and the residues 59 - 62, 214 - 217, 407 - 413) and protein P (Pf00336 and the residues 225 - 228). In HBV genome, seven RCCs were identified in the gene area of hepatitis core antigen, large envelope protein S and DNA polymerase, while protein structures of TrEMBL entries sequences found in Sherlocc program outputs were not complete.ConclusionsBased on the location of detected RCCs in the structure of HBV proteins, it was found that these RCCs may have a critical role in correct folding of HBV proteins and can be considered as drug targets. The results of this study provide new and deep perspectives about structure of HBV proteins for further researches and designing new drugs for treatment of HBV.

Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma.

To study the intrahepatic expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in chronic hepatitis B patients with and without hepatocellular carcinoma. A total of 33 chronic hepatitis B patients (mean age of 40.3 ± 2.5 years), comprising of 14 HBeAg positive and 19 HBeAg negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma (mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBcAg and HBsAg was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBcAg and HBsAg staining distributions and patterns were described according to a modified classification system. Compared to the HBeAg negative patients, the HBeAg positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBeAg positive patients had intrahepatic HBcAg staining; predominantly with "diffuse" distribution (79%) and "mixed cytoplasmic/nuclear" pattern (79%). In comparison, only 5% of the HBeAg-negative patients had intrahepatic HBcAg staining. However, the intrahepatic HBsAg staining has wider distribution among the HBeAg negative patients, namely; majority of the HBeAg negative cases had "patchy" HBsAg distribution compared to "rare" distribution among the HBeAg positive cases. All but one patient with HCC were HBeAg negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBcAg and HBsAg were seen in 13 (100%) and 10 (77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBcAg and HBsAg were detected in tumor tissues but not the adjacent liver in 4 (44%) and 1 (11%) patient respectively. Isolated intrahepatic HBcAg and HBsAg can be present in tumors of patients with suppressed HBV DNA on antiviral therapy; that may predispose them to cancer development.

Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation

ABSTRACTThe development of therapeutic vaccines against chronic hepatitis B requires the capacity of the formulation to subvert a tolerated immune response as well as the evaluation of histopathological damage resulting from the treatment. In the present study, the dynamicity of induced immune response to hepatitis B surface antigen (HBsAg) was evaluated in transgenic mice that constitutively express the HBsAg gene (HBsAg-tg mice). After immunization with a vaccine candidate containing both surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus (HBV), the effect of vaccination on clearance of circulating HBsAg and the potential histological alterations were examined. Transgenic (tg) and non-transgenic (Ntg) mice were immunized by intranasal (IN) and subcutaneous (SC) routes simultaneously. A control group received phosphate-buffered saline (PBS) by IN route and aluminum by SC route. Positive responses, at both humoral and cellular levels, were obtained after five immunizations in HBsAg-tg mice. Such responses were delayed and of lower intensity in tg mice, compared to vaccinated Ntg mice. Serum IgG response was characterized by a similar IgG subclass pattern. Even when HBsAg-specific CD8+ T cell responses were clearly detectable by gamma-interferon ELISPOT assay, histopathological alterations were not detected in any organ, including the liver and kidneys.Our study demonstrated, that it is possible to subvert the immune tolerance against HBsAg in tg mice, opening a window for new studies to optimize the schedule, dose, and formulation to improve the immune response to the therapeutic vaccine candidate. These results can be considered a safety proof to support clinical developments for the formulation under study.How to cite this articleFreyre FM, Blanco A, Trujillo H, Hernández D, García D, Alba JS, Lopez M, Merino N, Lobaina Y, Aguilar JC. Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation. Euroasian J Hepato-Gastroenterol 2016;6(1):25-30.