Surface Antigen Research Articles

Research Progress on Immune Evasion of Mycoplasma hyopneumoniae.

As the main pathogen associated with enzootic pneumonia (EP), Mycoplasma hyopneumoniae (Mhp) is globally prevalent and inflicts huge financial losses on the worldwide swine industry each year. However, the pathogenicity of Mhp has not been fully explained to date. Mhp invasion usually leads to long-term chronic infection and persistent lung colonization, suggesting that Mhp has developed effective immune evasion strategies. In this review, we offer more detailed information than was previously available about its immune evasion mechanisms through a systematic summary of the extant findings. Genetic mutation and post-translational protein processing confer Mhp the ability to alter its surface antigens. With the help of adhesins, Mhp can achieve cell invasion. And Mhp can modulate the host immune system through the induction of inflammation, incomplete autophagy, apoptosis, and the suppression of immune cell or immune effector activity. Furthermore, we offer the latest views on how we may treat Mhp infections and develop novel vaccines.

Antibody-Drug Conjugates: The New Treatment Approaches for Ovarian Cancer.

Ovarian cancer (OC), accounting for approximately 200,000 deaths worldwide annually, is a heterogeneous disease showing major differences in terms of its incidence, tumor behavior, and outcomes across histological subtypes. In OC, primary chemotherapy, paclitaxel carboplatin, bevacizumab, and PARP inhibitors have shown prolonged progression-free survival and a favorable overall response rate compared to conventional treatments. However, treatment options for platinum-resistant recurrence cases are limited, with no effective therapies that significantly prolong the prognosis. Recently, mirvetuximab soravtansine, an alpha-folate receptor (FRα)-targeted antibody-drug conjugate (ADC), was approved by the US Food and Drug Administration for patients with FRα-positive recurrent epithelial OC (EOC). This approval was based on a Phase II study, which demonstrated its efficacy in such patients. ADCs comprise an antibody, a linker, and a payload, representing new concept agents without precedence. Advanced clinical studies are developing ADCs for patients with OC, targeting solid tumors such as gynecologic cancer. Ongoing clinical trials are evaluating ADCs targeting FRα and human epidermal growth factor receptor 2, trophoblast cell surface antigen-2, sodium-dependent phosphate transport protein 2B, and cadherin-6 in Phase II/III studies. In this review, we summarize the existing evidence supporting the use of ADCs in OC, discuss ongoing clinical trials and preclinical studies, and explore the potential of these innovative agents to address the challenges in OC treatment.

Genetic diversity and natural selection analysis of VAR2CSA and vir genes: implication for vaccine development

Variable surface antigens (VSAs) encoded by var and vir genes in Plasmodium falciparum and Plasmodium vivax, respectively, are known to be involved in malaria pathogenesis and host immune escape through antigenic variations. Knowledge of the genetic diversity of these antigens is essential for malaria control and effective vaccine development. In this study, we analysed the genetic diversity and evolutionary patterns of two fragments (DBL2X and DBL3X) of VAR2CSA gene and four vir genes (vir 4, vir 12, vir 21 and vir 27) from different endemic regions, including Southeast Asia and sub-Saharan Africa. High levels of segregating sites (S) and haplotype diversity (Hd) were observed in both var and vir genes. Among vir genes, vir 12 (S = 131, Hd = 0.996) and vir 21 (S = 171, Hd = 892) were found to be more diverse as compared to vir 4 (S = 11, Hd = 0.748) and vir 27 (S = 23, Hd = 0.814). DBL2X (S = 99, Hd = 0.996) and DBL3X (S = 307, Hd = 0.999) fragments showed higher genetic diversity. Our analysis indicates that var and vir genes are highly diverse and follow the similar evolutionary pattern globally. Some codons showed signatures of positive or negative selection pressure, but vir and var genes are likely to be under balancing selection. This study highlights the high variability of var and vir genes and underlines the need of functional experimental studies to determine the most relevant allelic forms for effective progress towards vaccine formulation and testing.

Highly efficient strategy of lipopolysaccharide (LPS) decontamination from rHBsAg: synergistic effect of enhanced magnetic nanoparticles (MNPs) as an LPS affinity adsorbent (LAA) and surfactant as a dissociation factor

The interaction of lipopolysaccharide with a recombinant protein is a serious bottleneck, particularly in the purification step of bioprocessing. Recombinant hepatitis B surface antigen (rHBsAg), the active ingredient of the hepatitis B vaccine, is probably contaminated by extrinsic LPS like other biopharmaceuticals. This research intends to eliminate LPS from its mixture with rHBsAg efficiently. Immobilized polymyxin B on magnetic nanoparticles (PMB-MNPs) was synthesized and implemented as an enhanced LPS affinity adsorbent (LAA). The 20–80 EU/dose binary samples with and without surfactant were applied to PMB-MNPs. Formerly, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were examined on the samples to qualitatively show the dissociation effect of the surfactant. Considering the high potential interaction of LPS with HBsAg, the dissociation effects of 0.5 and 1.5% Tween 20 on the binary samples were assessed using immunoaffinity chromatography (IAC) as a quantification tool. The dissociation effect of Tween 20 substantially diminished the interaction, leading to a proportional increase of free LPS up to 66%. The synergetic effect of Tween 20 and privileged LAA was highly effective in eliminating more than 80% of LPS with a remarkable LPS clearance factor of 5.8 and a substantial protein recovery rate of 97%.

Prevalence of transfusion-transmitted infection and reactive donor response rate in a tertiary care hospital in South India: A retrospective observational study

Abstract Background: Transfusion-transmitted infections (TTIs) are a serious problem to our blood centers as they necessitate utilization of massive resources and labor to detect and remove infected blood donations and also turn out to be a source of great distress to the patients recieving blood components and the doctors treating them. The main diseases that are made mandatory by the government to be screened are hepatitis B virus, hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis. Adding to this, India does not have a centralized donor notification system to notify the donors of their TTI positivity status causing the blood centers to be blind and not having a system to verify the credentials of donors making sure they were not tested positive in other centers in the country. Materials and Methods: We have done a retrospective study that aims to analyze blood center samples and look for the number of TTI positivity in our donations and compare with the total number of donations during the period of January 2016 to March 2023. The data were collected from the blood donor questionnaire and data were put up in an Excel sheet which was later analyzed on the Statistical P program. Results: During the study period, 14,257 donors donated blood. Of which 11,674 (83%) were voluntary donors and 2413 (17%) were replacement donors. About 98.7% were male donors. Among the total donors, 182 (1.27%) were positive for transfusion-transmitted infections. Among the 182 serology-positive donors, 179 (98.3%) were males and 3 (1.7%) were females. Among the 14,257 donors, 160 (1.12%) were positive for hepatitis B surface antigen (HbsAg), 2 (0.014%) for HCV, 2 (0.014%) for HIV, and 18 (0.126%) for syphilis. Among the 182 positive TTI, 160 (87.9%) donors were positive for HBsAg, 18 (9.9%) were positive for syphilis, 2 (1.1%) donors with HIV, and 2 (1.1%) with HCV positivity. Among the 182 donors positive for TTI, 81 (44.5%) donors had donated previously in various hospitals and they were not aware of their positive status. Conclusion: This study mainly aims to bring awareness to the problems that blood centers face in TTI from having to screen every sample to independently verifying donors making sure that they have never tested positive for TTI and counseling them on further tests and referrals.

Detection of naturally acquired, strain-transcending antibodies against rosetting Plasmodium falciparum strains in humans.

Strain-transcending antibodies against virulence-associated subsets of P. falciparum-infected erythrocyte surface antigens could protect children from severe malaria. However, the evidence supporting the existence of such antibodies is incomplete and inconsistent. One subset of surface antigens associated with severe malaria, rosette-mediating Plasmodium falciparum Erythrocyte Membrane Protein one (PfEMP1) variants, cause infected erythrocytes to bind to uninfected erythrocytes to form clusters of cells (rosettes) that contribute to microvascular obstruction and pathology. Here, we tested plasma from 80 individuals living in malaria-endemic regions for IgG recognition of the surface of four P. falciparum rosetting strains using flow cytometry. Broadly reactive plasma samples were then used in antibody elution experiments in which intact IgG was eluted from the surface of infected erythrocytes and transferred to heterologous rosetting strains to look for strain-transcending antibodies. We found that seroprevalence (percentage of positive plasma samples) against allopatric rosetting strains was high in adults (63%-93%) but lower in children (13%-48%). Strain-transcending antibodies were present in nine out of eleven eluted antibody experiments, with six of these recognizing multiple heterologous rosetting parasite strains. One eluate had rosette-disrupting activity against heterologous strains, suggesting PfEMP1 as the likely target of the strain-transcending antibodies. Naturally acquired strain-transcending antibodies to rosetting P. falciparum strains in humans have not been directly demonstrated previously. Their existence suggests that such antibodies could play a role in clinical protection and raises the possibility that conserved epitopes recognized by strain-transcending antibodies could be targeted therapeutically by monoclonal antibodies or vaccines.

One-Step Formation Method of Plasmid DNA-Loaded, Extracellular Vesicles-Mimicking Lipid Nanoparticles Based on Nucleic Acids Dilution-Induced Assembly.

We propose a nucleic acids dilution-induced assembly (NADIA) method for the preparation of lipid nanoparticles. In the conventional method, water-soluble polymers such as nucleic acids and proteins are mixed in the aqueous phase. In contrast, the NADIA method, in which self-assembly is triggered upon dilution, requires dispersion in an alcohol phase without precipitation. We then investigated several alcohols and discovered that propylene glycol combined with sodium chloride enabled the dispersion of plasmid DNA and protamine sulfate in the alcohol phase. The streamlined characteristics of the NADIA method enable the preparation of extracellular vesicles-mimicking lipid nanoparticles (ELNPs). Among the mixing methods using a micropipette, a syringe pump, and a microfluidic device, the lattermost was the best for decreasing batch-to-batch differences in size, polydispersity index, and transfection efficiency in HepG2 cells. Although ELNPs possessed negative ζ-potentials and did not have surface antigens, their transfection efficiency was comparable to that of cationic lipoplexes. We observed that lipid raft-mediated endocytosis and macropinocytosis contributed to the transfection of ELNPs. Our strategy may overcome the hurdles linked to supply and quality owing to the low abundance and heterogeneity in cell-based extracellular vesicles production, making it a reliable and scalable method for the pharmaceutical manufacture of such complex formulations.

Establishment of a hepatitis B virus reporter system harboring a HiBiT-tag in the PreS2 region.

Approximately 296 million people suffer from chronic hepatitis B (CHB) caused by hepatitis B virus (HBV). Current standard treatment, nucleos(t)ide analogs, are not efficient enough to eradicate HBV from the hepatocytes. Thus, developing new drugs for CHB is desired to achieve complete cure. Here we established a novel HBV reporter system, HBV-HiBiT-PS2, to screen new drugs for CHB. HBV-HiBiT-PS2 was constructed by introducing a HiBiT-tag at the 5'-end of PreS2 and introduced into HepG2-NTCP cells. Culture supernatant containing HBV-HiBiT-PS2 virions was fractionated by a sucrose density gradient ultracentrifugation to characterize their components. Replication kinetics and reporter function of HBV-HiBiT-PS2 were determined by analyzing the parameters for HBV replication in the presence or absence of HBV inhibitors. HBV-HiBiT-PS2 could be used for monitoring most of the replication cycle of HBV. The effects of well-characterized HBV inhibitors could be evaluated by the HiBiT activity. HBV-HiBiT-PS2 could be specialized for screening secretion inhibitors for hepatitis B surface antigen (HBsAg) because most of the HiBiT activity was derived from subviral particles which are the multimers of HBsAg. We demonstrated that HBV-HiBiT-PS2 would be a robust tool for screening novel drugs, especially HBsAg secretion inhibitors, targeted for CHB.

Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics

Background and aimsThe intrahepatic processes associated with chronic hepatitis B (CHB), especially in the context of hepatitis delta virus (HDV) and HIV co-infection, require a better understanding. Spatial transcriptomics can...

Prevalence of HBV genotypes among patients attending Moi Teaching and Referral Hospital liver clinic.

Hepatitis B virus (HBV) belongs to the genus Orthohepadnavirus, of Hepadnaviridae family, smallest human deoxyribonucleic acid (DNA) virus with 3200 bp in a partially double-stranded circular DNA. Globally, about 2 billion people are infected with over 65 million of the chronically infected residing in Africa. Ten HBV genotypes (A-J) have been reported across the globe. Based on the World Health Organization (WHO) African Regions including Kenya have high HBV prevalence rates yet the data on prevalence rates of the various HBV genotypes and their associated biomarkers is very scanty. A cross-sectional descriptive study with purposive sampling was conducted in which a census of patients with chronic Hepatitis B (CHB) with history >6-month were reviewed for eligibility. Demographics data was abstracted from patient files and blood samples drawn for genotyping, viral load using Rotor gene Q Polymerase Chain Reaction (PCR) equipment, Hepatitis B surface Antigen (HBsAg), Hepatitis B envelope antigen (HbeAg) and Hepatitis B core antibody (Anti-HBc) using Cobas e411 machine. Out of a total of 83 patients, 43 (52%) were eligible; males 29 (67.4%), females 14 (32.6%) with mean ages of 35.1±10.8 and 34.3±9.3 respectively. Genotypes A were 34(79.1%), B were 5(11.6%), C-D were 0 while E-J were 9(20.9%). All cases of genotype B were associated with co-infection of genotype A. Majority were HBeAg negative with HBV DNA >10 IU/ml (81.4% and 86.0% respectively) with distribution among all the genotypes. Across genotypes, viral load mean percentage comparisons were: A vs. A/B = 2600 (p = 0.09), A vs. E-J = 5260 (p = 0.09) and A/B vs. E-J = 200 (p = 0.28). The most prevalent genotype was A followed by mixed co-infection of genotype A/B. Genotype A was associated with HBV DNA viral loads > 10IU/ml and high rates of HBeAg negativity. Genotypes E-J were also detected though not characterized.

Testing for Hepatitis B and C virus and HIV in mental healthcare settings in England between 2015–2021

People living with severe mental illness have an increased prevalence of bloodborne viruses (BBVs) such as hepatitis B (HBV) and hepatitis C viruses (HCV), and HIV. To help improve the physical health of people living with severe mental illness, we aim to understand associations with BBV testing and treatment provision among those tested in mental healthcare settings in England. HBV surface antigen [HBsAg], antibody HCV [anti-HCV] and HIV testing and demographic information pertaining to people tested in mental health settings in England were extracted from a BBV testing dataset. Records pertaining to individuals diagnosed with HCV or HIV were linked to treatment datasets. Multivariable logistic regression analyses were used to understand demographic associations with test positivity for each BBV. Between 2015–2021, 18,221 people tested for a BBV in a mental health setting (56% male, 71% White ethnicity), 90% of whom were in inpatient care. Testing positive for HBsAg, anti-HCV and HIV was 1.1% (95%CI: 0.93–1.26%), 4.3% (4.00–4.63%) and 1.1% (0.92–1.25%) respectively. In multivariable analyses, women had reduced odds of testing positive for anti-HCV and HIV compared to men. Being of Asian, Black, or another ethnicity was associated with increased odds of testing HBsAg positive and Black ethnicity was associated with a positive HIV test result compared to White ethnicity. White ethnicity was associated with testing anti-HCV test positive compared to all other ethnicities. Half (344/708) of those who were anti-HCV positive would have benefitted from treatment (HCV-RNA positive), of which 58% received treatment. HIV treatment (96%) and viral suppression (94%) after testing in mental healthcare was high. To improve the physical health of people living with mental health conditions and to aid England’s hepatitis elimination and HIV transmission goals, opt-out testing for BBVs may be beneficial to reduce health inequalities among people experiencing mental illness.

Neural Network Enables High Accuracy for Hepatitis B Surface Antigen Detection with a Plasmonic Platform.

The detection of hepatitis B surface antigen (HBsAg) is critical in diagnosing hepatitis B virus (HBV) infection. However, existing clinical detection technologies inevitably cause certain inaccuracies, leading to delayed or unwarranted treatment. Here, we introduce a label-free plasmonic biosensing method based on the thickness-sensitive plasmonic coupling, combined with supervised deep learning (DL) using neural networks. The strategy of utilizing neural networks to process output data can reduce the limit of detection (LOD) of the sensor and significantly improve the accuracy (from 93.1%-97.4% to 99%-99.6%). Compared with widely used emerging clinical technologies, our platform achieves accurate decisions with higher sensitivity in a short assay time (∼30 min). The integration of DL models considerably simplifies the readout procedure, resulting in a substantial decrease in processing time. Our findings offer a promising avenue for developing high-precision molecular detection tools for point-of-care (POC) applications.

A pilot integrated model nurse clinic increases the uptake of antiviral treatment for the prevention of mother-to-child transmission of HBV.

Mother-to-child-transmission (MTCT) of hepatitis B virus (HBV) may still occur despite birth-dose HBV vaccinations when pregnant women are positive for hepatitis B surface antigen (HBsAg) with high viral loads (HBV DNA ≥ 200 000 IU/mL). A pilot integrated model nurse clinic (IMNC) was started in 2020 to implement the pre-emptive antiviral therapy with tenofovir disoproxil fumarate (TDF). We aimed to evaluate the performance of IMNC on uptake of TDF. This was a territory-wide retrospective cohort of all consecutive HBsAg-positive women of child-bearing age with pregnancy records in public hospitals 2019-2022. Demographic characteristics, liver biochemistries and virologic parameters, and TDF use were collected. Concurrently, data from a prospective audit in Union Hospital, the private hospital with the highest number of deliveries in Hong Kong, from June 2022 to May 2023 were compared. The prevalence rate of HBV DNA ≥ 200 000 IU/mL in pregnant women with available HBV DNA records was 29.2% (66/226) in 2019, 27.3% (99/363) in 2020, 15.9% (125/784) in 2021 and 17.2% (117/679) in 2022 (p < .001), out of 2052 pregnant women who had their HBV DNA checked within 1 year prior to delivery. An increasing uptake rate of TDF by highly viraemic pregnant women (i.e. ≥ 200 000 IU/mL) was noted after the commencement of IMNC in public hospitals, with 67% (45/67) in 2019, 83% (88/106) in 2020, 91% (117/128) in 2021 and 89% (149/167) in 2022. Moreover, all highly viraemic pregnant women from Union Hospital received TDF. Continuous use of TDF was associated with a reduced risk of postpartum biochemical flare. IMNC increases the uptake of antiviral treatment in pregnant women at risk of MTCT of HBV. IMNC contributes to hepatitis elimination through a structured care plan to prevent MTCT of HBV.

Trajectories of serum HBsAg during treatment and association with HBsAg loss in children with HBeAg-positive chronic hepatitis B: a latent class trajectory analysis.

The change of serum hepatitis B surface antigen (HBsAg) during treatment are associated with HBsAg loss. However, little is known about the trajectory patterns of HBsAg in early treatment and their relationship with subsequent HBsAg loss. This study aimed to identify trajectories of HBsAg in children with HBeAg-positive chronic hepatitis B (CHB) and investigate the association between trajectory patterns and HBsAg loss. A retrospective study was conducted on 166 treatment-naive children with HBeAg-positive CHB. Latent class trajectory analysis was used to identify trajectory groups of serum HBsAg. Cox proportional hazard model was used to assess the association between HBsAg trajectory groups and HBsAg loss. The median follow-up time was 20.70 (12.54, 34.17) months, and HBsAg loss occurred in 70(42.17%) of all study participants. Using latent class trajectory analysis, HBeAg-positive CHB patients were classified into three trajectory groups: trajectory 1 (sustained stability, 24.70%), trajectory 2 (slow decline, 38.55%), and trajectory 3 (rapid decline, 36.75%), respectively. The median decline levels of HBsAg at the 3-month and 6-month follow-ups were the highest in trajectory 3 (1.08 and 3.28 log10 IU/ml), followed by trajectory 2 (0.27 and 1.26 log10 IU/ml), and no change in trajectory 1. The risk of achieving HBsAg loss was higher in both trajectory 2 (HR, 3.65 [95% CI, 1.70-7.83]) and trajectory 3 (HR, 7.27 [95% CI, 3.01-17.61]), respectively. Serum HBsAg levels during early treatment can be classified into distinct trajectory groups, which may serve as an additional predictive indicator for HBsAg loss in HBeAg-positive CHB children.

Single-cell analysis of treatment-resistant prostate cancer: Implications of cell state changes for cell surface antigen–targeted therapies

Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly cell surface molecules, varies in the process of lineage plasticity, wherein tumor cells alter their identity and acquire new oncogenic properties. A notable example of lineage plasticity is the transformation of prostate adenocarcinoma (PRAD) to neuroendocrine prostate cancer (NEPC)-a growing resistance mechanism that results in the loss of responsiveness to androgen blockade and portends dismal patient survival. To understand how lineage markers vary across the evolution of lineage plasticity in prostate cancer, we applied single-cell analyses to 21 human prostate tumor biopsies and two genetically engineered mouse models, together with tissue microarray analysis on 131 tumor samples. Not only did we observe a higher degree of phenotypic heterogeneity in castrate-resistant PRAD and NEPC than previously anticipated but also found that the expression of molecules targeted therapeutically, namely PSMA, STEAP1, STEAP2, TROP2, CEACAM5, and DLL3, varied within a subset of gene-regulatory networks (GRNs). We also noted that NEPC and small cell lung cancer subtypes shared a set of GRNs, indicative of conserved biologic pathways that may be exploited therapeutically across tumor types. While this extreme level of transcriptional heterogeneity, particularly in cell surface marker expression, may mitigate the durability of clinical responses to current and future antigen-directed therapies, its delineation may yield signatures for patient selection in clinical trials, potentially across distinct cancer types.

A Label-free Optical Biosensor-Based Point-of-Care Test for the Rapid Detection of Monkeypox Virus.

Diagnostic approaches that combine the high sensitivity and specificity of laboratory-based digital detection with the ease of use and affordability of point-of-care (POC) technologies could revolutionize disease diagnostics. This is especially true in infectious disease diagnostics, where rapid and accurate pathogen detection is critical to curbing the spread of disease. We have pioneered an innovative label-free digital detection platform that utilizes Interferometric Reflectance Imaging Sensor (IRIS) technology. IRIS leverages light interference from an optically transparent thin film, eliminating the need for complex optical resonances to enhance the signal by harnessing light interference and the power of signal averaging in shot-noise-limited operation to achieve virtually unlimited sensitivity. In our latest work, we have further improved our previous 'Single-Particle' IRIS (SP-IRIS) technology by allowing the construction of the optical signature of target nanoparticles (whole virus) from a single image. This new platform, 'Pixel-Diversity' IRIS (PD-IRIS), eliminated the need for z-scan acquisition, required in SP-IRIS, a time-consuming and expensive process, and made our technology more applicable to POC settings. Using PD-IRIS, we quantitatively detected the Monkeypox virus (MPXV), the etiological agent for Monkeypox (Mpox) infection. MPXV was captured by anti-A29 monoclonal antibody (mAb 69-126-3) on Protein G spots on the sensor chips and were detected at a limit-of-detection (LOD) - of 200 PFU/ml (~3.3 attomolar). PD-IRIS was superior to the laboratory-based ELISA (LOD - 1800 PFU/mL) used as a comparator. The specificity of PD-IRIS in MPXV detection was demonstrated using Herpes simplex virus, type 1 (HSV-1), and Cowpox virus (CPXV). This work establishes the effectiveness of PD-IRIS and opens possibilities for its advancement in clinical diagnostics of Mpox at POC. Moreover, PD-IRIS is a modular technology that can be adapted for the multiplex detection of pathogens for which high-affinity ligands are available that can bind their surface antigens to capture them on the sensor surface.

Discovery of hepatitis B virus subviral particle biogenesis inhibitors from a bioactive compound library

High levels of hepatitis B virus (HBV) surface antigen (HBsAg) in the blood of chronic HBV carriers are considered to drive the exhaustion of antigen-specific T and B lymphocytes and thus responsible for the persistence of infection. Accordingly, therapeutic elimination of HBsAg may facilitate the activation of adaptive antiviral immune responses against HBV and achieve a functional cure of chronic hepatitis B. We discovered recently that an amphipathic alpha helix spanning W156 to R169 of HBV small envelope (S) protein plays an essential role in the morphogenesis of subviral particles (SVPs) and metabolism of S protein. We thus hypothesized that pharmacological disruption of SVP morphogenesis may induce intracellular degradation of S protein and reduce HBsAg secretion. To identify inhibitors of SVP biogenesis, we screened 4417 bioactive compounds with a HepG2-derived cell line expressing HBV S protein and efficiently secreting small spherical SVPs. The screen identified 24 compounds that reduced intracellular SVPs and secreted HBsAg in a concentration-dependent manner. However, 18 of those compounds inhibited the secretion of HBsAg and HBeAg in HBV replicon transfected HepG2 cells at similar efficiency, suggesting each of those compounds may disrupt a common cellular function required for the synthesis and/or secretion of these viral proteins. Interestingly, lycorine more efficiently inhibited the secretion of HBsAg in HepG2 cells transfected with HBV replicons, HepG2.2.15 cells and HBV infected - HepG2 cells expressing sodium taurocholate cotransporting polypeptide (NTCP). The structure activity relationship and antiviral mechanism of lycorine against HBV have been determined.

Seroprevalence of transfusion -transmitted infections among blood donors in a tertiary care hospital in and around Koodapakkam, Puducherry, India

Introduction: Even though blood transfusion safety has come a long way, Transfusion-Transmitted Infections (TTI), which include bacterial, viral, parasitic, and prions, can still spread with each transfusion. The main goal of this study was to determine the seroprevalence of the five TTIs that are required to be tested in India among blood donors at our facility. Accurate estimates of the risk of TTIs are essential for monitoring the safety of the blood supply. Methodology: This was a retrospective descriptive study conducted in the blood centre of a tertiary care teaching hospital in Puducherry, from 2017 to 2023. Records from blood banks were reviewed to collect data on all donors who underwent appropriate testing for HIV, hepatitis C, Hepatitis B, syphilis, and malaria. Enzyme-linked immunosorbent assay was done for HIV, HCV, HBsAg/hepatitis B surface antigen, and rapid card testing was done for syphilis and malaria. Results: There was a total of 2570 donors during the study period. In the present study, the overall seroprevalence of TTIs was 1.40%. The individual seropositivity rates were 0.03% for HIV, 0.93 % for HBsAg, and 0.43 % for syphilis. There were no cases of malaria and HCV detected in the study period. The highest percentage of prevalence was observed for HBV, followed by Syphilis and HIV. Conclusion: The overall seroprevalence of TTI in Puducherry was smaller than those reported elsewhere in the country. It was comparatively lesser than the national average for HIV, HCV, and HBV and much higher for syphilis.

Morphologic, cytometric, quantitative transcriptomic and functional characterisation provide insights into the haemocyte immune responses of Pacific abalone (Haliotis discus hannai).

In recent years, the abalone aquaculture industry has been threatened by the bacterial pathogens. The immune responses mechanisms underlying the phagocytosis of haemocytes remain unclear in Haliotis discus hannai. It is necessary to investigate the immune mechanism in response to these bacterial pathogens challenges. In this study, the phagocytic activities of haemocytes in H. discus hannai were examined by flow cytometry combined with electron microscopy and transcriptomic analyses. The results of Vibrio parahaemolyticus, Vibrio alginolyticus and Staphylococcus aureu challenge using electron microscopy showed a process during phagosome formation in haemocytes. The phagocytic rate (PP) of S. aureus was higher than the other five foreign particles, which was about 63%. The PP of Vibrio harveyi was about 43%, the PP peak of V. alginolyticus in haemocyte was 63.7% at 1.5h. After V. parahaemolyticus and V. alginolyticus challenge, acid phosphatase, alkaline phosphatase, total superoxide dismutase, lysozyme, total antioxidant capacity, catalase, nitric oxide synthase and glutathione peroxidase activities in haemocytes were measured at different times, differentially expressed genes (DEGs) were identified by quantitative transcriptomic analysis. The identified DEGs after V. parahaemolyticus challenge included haemagglutinin/amebocyte aggregation factor-like, supervillin-like isoform X4, calmodulin-like and kyphoscoliosis peptidase-like; the identified DEGs after V. alginolyticus challenge included interleukin-6 receptor subunit beta-like, protein turtle homolog B-like, rho GTPase-activating protein 6-like isoform X2, leukocyte surface antigen CD53-like, calponin-1-like, calmodulin-like, troponin C, troponin I-like isoform X4, troponin T-like isoform X18, tumor necrosis factor ligand superfamily member 10-like, rho-related protein racA-like and haemagglutinin/amebocyte aggregation factor-like. Some immune-related KEGG pathways were significantly up-regulated or down-regulated after challenge, including thyroid hormone synthesis, Th17 cell differentiation signalling pathway, focal adhesion, melanogenesis, leukocyte transendothelial migration, inflammatory mediator regulation of TRP channels, ras signalling pathway, rap1 signalling pathway. This study is the first step towards understanding the H. discus hannai immune system by adapting several tools to gastropods and providing a first detailed morpho-functional study of their haemocytes.

Incidences of new hepatitis B infection and anti-hepatitis B core-negative occult hepatitis B infection among Japanese blood donors in relation to anti-hepatitis B surface antigen levels.

A transfusion-transmitted hepatitis B virus (HBV) infection caused by blood only positive for anti-hepatitis B surface antigen (anti-HBs) was reported. Occult HBV infection (OBI) with sole anti-HBs among blood donors is an issue. The incidence of HBV infection among repeat blood donors was investigated with a detailed HBV infection phase, focusing on the influence of anti-HBs level. This study followed 3 435 653 donors for HBV DNA conversion over 4 years and 9 months. Infection phase was determined based on marker changes over DNA conversion. This study identified 115 hepatitis B surface antigen (HBsAg) conversions, 72 DNA-only conversions, and 15 DNA plus anti-hepatitis B core (anti-HBc) conversions among donors all negative for HBV DNA, HBsAg, and anti-HBc. Total incidence was 2.38/100 000 person-years (PY). None of these 202 new HBV infections arose in the group with anti-HBs titer ≥ 10 mIU/mL. In total, 30 anti-HBc-negative OBIs were identified (incidence; 0.35/100 000 PY); 7 showed typical secondary anti-HBs response, and 23 showed stable anti-HBc and anti-HBs levels at DNA conversion. The HBV infection-protective ability of anti-HBs ≥ 10 mIU/mL was reinforced. In addition to new infections, the blood donor population includes anti-HBc-positive- and negative OBI with immune reactions or abortive HBV infection.