Virus Surface Antigen Research Articles

Clinical presentation, viral kinetics, and management of human monkeypox cases from New Delhi, India 2022.

We describe the clinical and demographic characteristics, virological follow-up, and management of five confirmed monkeypox cases from New Delhi, India without any international travel history. The viral load kinetics and viral clearance were estimated in oropharyngeal swabs (OPS), nasopharyngeal swabs (NPS), EDTA blood, serum, urine, and various lesion specimens on every fourth day of follow-up ranging from 5 to 24 post onset day (POD) of illness. Allfive cases presented with mild to moderate-grade intermittent fever, myalgia, and lesions on the genitals, groins, lower limb, trunk, and upper limb. Four cases had non-tender firm lymphadenopathy. No secondary complications or sexually transmitted infections were recorded in these cases except for the presence of viral hepatitis B infection marker hepatitis B virus surface antigen(HBsAg) in one case. All the cases were mild and had a good recovery. Ahigher viral load was detected in lesion fluid (POD 9), followed by lesion roof (POD 9), urine (POD 5), lesion base (POD 5), and OPS/NPS (POD 5). The monkeypox virus(MPXV) DNA was detected in clinical samples from 5th to 24th POD. These monkeypox cases without international travel history suggest the underdiagnosed monkeypox infection in the community. This emphasizes the need for active surveillance of MPXV in the high-risk population such as men having sex with men and female sex workers.

Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice

Rapid antigenic evolution of the influenza A virus surface antigen hemagglutinin undermines protection conferred by seasonal vaccines. Protective correlates targeted by universal vaccines such as cytotoxic T cells or HA stem directed broadly neutralizing antibodies have been shown to select for immune escape mutants during infection. We developed an in vivo serial passage mouse model for viral adaptation and used next generation sequencing to evaluate full genome viral evolution in the context of broadly protective immunity. Heterosubtypic immune pressure increased the incidence of genome-wide single nucleotide variants, though mutations found in early adapted populations were predominantly stochastic in nature. Prolonged adaptation under heterosubtypic immune selection resulted in the manifestation of highly virulent phenotypes that ablated vaccine mediated protection from mortality. High frequency mutations unique to escape phenotypes were identified within the polymerase encoding segments. These findings suggest that a suboptimial usage of population-wide universal influenza vaccine may drive formation of escape variants attributed to polygenic changes.

Virological responses to tenofovir-alafenamide-containing antiretroviral therapy in people living with HIV co-infected with lamivudine-resistant or lamivudine-susceptible hepatitis B virus

BackgroundData on the effectiveness of tenofovir alafenamide (TAF) against lamivudine-resistant (LAM-R) hepatitis B virus (HBV) among patients co-infected with human immunodeficiency virus (HIV) and HBV are limited. MethodsBetween April and December 2018, HIV-positive patients co-infected with LAM-R or lamivudine-susceptible (LAM-S) HBV who switched from tenofovir-disoproxil-fumarate-containing antiretroviral therapy (ART) to TAF-containing ART were followed for 96 weeks. Plasma HBV and HIV loads, HBV serological markers, and liver function before and after the switch were analysed. ResultsIn total, 182 patients co-infected with HIV and HBV were included in this study: 45 with LAM-R HBV and 137 with LAM-S HBV. At baseline, 28.9% and 7.4% of patients in the LAM-R and LAM-S groups, respectively, tested positive for hepatitis B virus envelope antigen (HBeAg) (P<0.001), and the respective percentages of patients who had achieved plasma HBV DNA <20 IU/mL were 95.5% and 97.1%. At weeks 48 and 96, 100% and 94.9% of patients in the LAM-R group, respectively, and 97.1% and 95.6% of patients in the LAM-S group, respectively, maintained plasma HBV DNA <20 IU/mL. Lamivudine resistance of HBV and baseline hepatitis B virus surface antigen (HBsAg) level were associated with HBsAg decrement at week 96 at a degree of 0.25 log10 IU/mL [95% confidence interval (CI) 0.059–0.246] and 0.22 log10 IU/mL (per 1-log10IU/mL increase, 95% CI 0.018–0.101), respectively. At week 96, 2.2% (4/182) of patients had HBsAg loss; no patients in the LAM-R group and 25.0% (2/8) of patients in the LAM-S group had HBeAg seroconversion. ConclusionsSwitching to TAF-containing regimens maintained high rates of HBV viral suppression in patients co-infected with either LAM-R or LAM-S HBV. The decrease in HBsAg was minimal, and HBsAg seroconversion occurred infrequently.

Long-term outcome of lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients

BackgroundThe use of DTG-containing two-drug regimens is one of the most promising solutions to the need to ease the management of HIV treatment without harming its efficacy and safety. We report long- term results in patients switched, while virologically suppressed, to the combination of dolutegravir (DTG) plus lamivudine (3TC).MethodsThis is a prospective, clinical, uncontrolled cohort enrolling ART-experienced people living with HIV (PLWH) with HIV-RNA < 50 copies/ml for 6 months or longer, negative hepatitis B virus surface antigen, and without known M184V/I mutations. Kaplan-Meiers curves are used to describe persistency of virological suppression on therapy and a Cox regression model to evaluate baseline characteristics and the risk of stopping therapy.Results218 individuals switched their regimen since 2015. The mean estimated follow-up was of 64.3 months (95% CI 61.3–67.3) for approximately 1000 patient/years. After 5 years of follow-up, 77.1% were still on the DTG-3TC combination. No virologic failure was detected throughout the whole study period, and only 15 subjects presented single isolated viral blips above 50 copies/ml. Most patients stopped therapy because of reasons unrelated to study drugs (lost to follow-up; patients’ decision; moved to other Centers), but due to the unselected nature of the casuistry; 11 subjects died in the 5 years of follow-up mostly because of pre-existing co-morbidities (6 neoplastic diseases and 2 end-stage liver disease). The median baseline CD4 count was 669 cells/mcl (IQR 483–927). After 5 years it raised to 899 cells/mcl (IQR 646–1160) (P < 0.001) without a significant change of CD8 counts that lowered from 767 cells/mcl (IQR 532–1034) to 683 cells/mcl (IQR 538–988). Consequently, the CD4/CD8 ratio varied from 0.93 (IQR 0.60–1.30) to 1.15 (IQR 0.77–1.45) (P < 0.0001). A non-significant (P = 0.320) increment of mean creatinine, 0.06 mg/dl in magnitude, was observed over the whole follow-up.ConclusionThese long-term results over 5 years reinforce the durability and good tolerability of DTG-3TC. Our results continue to support the recommended switch use of this 2DR as a well-accepted treatment option for ART-experienced PLWH.

Investigate the Presence of HBV Surface Antigen in Pregnant Women, Cairo City in Egypt.

Hepatitis means inflammation of the liver, and hepatitis B is a common and dangerous liver disease caused by the Hepatitis B Virus (HBV) of the DNA hepadnavirus family. In 2010, the World Health Organization (WHO) considered hepatitis B infection a major health problem worldwide. One way of transmitting this disease is a transmission from a carrier mother to a child. This study aimed to investigate the presence of HBV surface antigen in pregnant women referred to Kasra Al-Aini Hospital in Cairo. This study was a cross-sectional descriptive study that was performed on pregnant women. One thousand pregnant women were selected with their consent to participate in this study, and after preparing a blood sample, an Enzyme-linked Immunosorbent Assay kit, used for Hepatitis B Virus surface antigen detection, a questionnaire containing questions about socio-individual characteristics. Among 1000 samples, 13 samples were equal to 1.3% had HBsAg positive. No significant relationship was found between the prevalence of HBs Ag in the city and rural location, education, occupation, age, and history of abortion in pregnant women. History of dialysis in pregnant women, tattooing, and type of job of the pregnant woman was not considered risk factors. However, injection drug users, history of previous surgery, and blood transfusion can be considered suspicious factors (P≤0.05). The prevalence of hepatitis B infection in pregnant women in Cairo was 1.3, which is lower than the study statistics in most parts of the world. However, to evaluate this amount more accurately, there is a need to conduct a study with a higher sample size.

Presence of Intact Hepatitis B Virions in Exosomes

Hepatitis B virus (HBV) was identified as an enveloped DNA virus with a diameter of 42 nm. Multivesicular bodies play a central role in HBV egress and exosome biogenesis. In light of this, it was studied whether intact virions wrapped in exosomes are released by HBV-producing cells. Robust methods for efficient separation of exosomes from virions were established. Exosomes were subjected to limited detergent treatment for release of viral particles. Electron microscopy of immunogold labeled ultrathin sections of purified exosomes was performed for characterization of exosomal HBV. Exosome formation/release was affected by inhibitors or Crispr/Cas-mediated gene silencing. Infectivity/uptake of exosomal HBV was investigated in susceptible and non-susceptible cells. Exosomes could be isolated from supernatants of HBV-producing cells, which are characterized by the presence of exosomal and HBV markers. These exosomal fractions could be separated from the fractions containing free virions. Limited detergent treatment of exosomes causes stepwise release of intact HBV virions and naked capsids. Inhibition of exosome morphogenesis impairs the release of exosome-wrapped HBV. Electron microscopy confirmed the presence of intact virions in exosomes. Moreover, the presence of large hepatitis B virus surface antigen on the surface of exosomes derived from HBV expressing cells was observed, which conferred exosome-encapsulated HBV initiating infection in susceptible cells in a , large hepatitis B virus surface antigen/Na+-taurocholate co-transporting polypeptide-dependent manner. The uptake of exosomal HBV with low efficiency was also observed in non-permissive cells. These data indicate that a fraction of intact HBV virions can be released as exosomes. This reveals a so far not described release pathway for HBV.

A machine learning-based SNP-set analysis approach for identifying disease-associated susceptibility loci

Identifying disease-associated susceptibility loci is one of the most pressing and crucial challenges in modeling complex diseases. Existing approaches to biomarker discovery are subject to several limitations including underpowered detection, neglect for variant interactions, and restrictive dependence on prior biological knowledge. Addressing these challenges necessitates more ingenious ways of approaching the “missing heritability” problem. This study aims to discover disease-associated susceptibility loci by augmenting previous genome-wide association study (GWAS) using the integration of random forest and cluster analysis. The proposed integrated framework is applied to a hepatitis B virus surface antigen (HBsAg) seroclearance GWAS data. Multiple cluster analyses were performed on (1) single nucleotide polymorphisms (SNPs) considered significant by GWAS and (2) SNPs with the highest feature importance scores obtained using random forest. The resulting SNP-sets from the cluster analyses were subsequently tested for trait-association. Three susceptibility loci possibly associated with HBsAg seroclearance were identified: (1) SNP rs2399971, (2) gene LINC00578, and (3) locus 11p15. SNP rs2399971 is a biomarker reported in the literature to be significantly associated with HBsAg seroclearance in patients who had received antiviral treatment. The latter two loci are linked with diseases influenced by the presence of hepatitis B virus infection. These findings demonstrate the potential of the proposed integrated framework in identifying disease-associated susceptibility loci. With further validation, results herein could aid in better understanding complex disease etiologies and provide inputs for a more advanced disease risk assessment for patients.

Liver-Related Mortality in Hepatitis B Virus Core Antibody+/Hepatitis B Virus Surface Antigen- Patients: Occult Hepatitis B Virus, Hepatitis B Virus Reactivation, and Hepatocellular Carcinoma Development.

Although hepatitis B virus surface antigen (HBsAg) serum clearance is an important milestone in the natural history of chronic hepatitis B virus (HBV) infection, HBsAg-negative patients are at risk of liver cancer and liver-related death, especially when progressive fibrosis is present. HBsAg-negative/anti-HBV core antibody-positive patients should be carefully evaluated and managed accordingly for the presence of significant liver fibrosis, other viral coinfections, occult HBV infection, risk of HBV reactivation, and hepatocellular carcinoma. Antiviral prophylaxis should be initiated in isolated anti-HBV core antibody patients receiving high-risk chemotherapy or biologics. Hepatocellular carcinoma surveillance with liver ultrasound and serum alpha-fetoprotein should be considered for patients with risk factors.

Seroprevalence of Hepatitis A, B and C Among a Sample of Refugees in Egypt: An Exploratory Survey

BackgroundEstimating the prevalence of infectious diseases, including viral hepatitis, among refugees is important for evaluating their health needs and predicting the burden on the health system of the host country. This study aimed at estimating the seroprevalence of viral hepatitis among refugees in Egypt.MethodsThis cross-sectional study involved a heterogeneous group of 501 refugees. Enzyme-linked immunosorbent assays were used to detect IgG antibodies against hepatitis A virus (HAV), B virus (HBV) surface antigen (anti-HBsAg), C virus (HCV), and HBV surface antigen (HBsAg).ResultsAnti-HAV was the most prevalent marker (n = 482, 96.2%), followed by anti-HBs (n = 142, 28.3%) and HBsAg (n = 21, 4.2%), while only four refugees (0.8%) had positive anti-HCV IgG. Anti-HBs was higher in males (p < 0.05). Older refugees and non-working subjects had significantly higher seropositive rates of anti-HAV (p = 0.051 and p = 0.023, respectively), while students and those below 15 years of age had higher rates of anti-HBs (p < 0.05). Positive HBsAg results were associated with history of hepatitis (p < 0.001). Obese participants were more likely to be positive for HBsAg (p = 0.025) and anti-HBs (p < 0.05). Sudanese refugees had significantly higher rates of anti-HAV antibodies (p = 0.049), while Yemini refugees had significantly higher rates for HBsAg (p = 0.019) positivity. Residents of Dakahlia had significantly higher rates of anti-HAV (p = 0.008) and anti-HBs (p < 0.05). None of the studied risk factors was significantly associated with anti-HCV.ConclusionRefugees in Egypt have poor immunity against HBV with intermediate to high HBV and low HCV prevalence rates. Despite that 65% of refugees received the HAV vaccine, almost all had IgG anti-HAV, denoting previous infection.

Improved Aluminum Adjuvants Eliciting Stronger Immune Response When Mixed with Hepatitis B Virus Surface Antigens.

Adjuvants can regulate the immune response triggered by vaccines. Traditional aluminum adjuvants can induce humoral immunity, but they lack the ability to effectively induce Th1 cellular immunity, which is not conducive to the development of vaccines with improved protective effects. Aluminum adjuvants from different sources may have different physicochemical properties, and therefore, completely different immune responses can be triggered. This suggests that adjuvant recognition by the immune system and its responses are closely associated with the physicochemical properties of the adjuvant itself. To test this hypothesis, in this study, we developed a new method for preparing an aluminum adjuvant. This aluminum adjuvant has a pseudoboehmite structure, strong protein adsorption capacity, and excellent suspension stability. The adjuvant was tested using the hepatitis B virus surface antigen (HBsAg) as a model antigen for immunization; the results showed that this aluminum adjuvant effectively induced not only humoral immunity but also an outstanding cellular immune response. These results provide a reference for improving the efficacy of adjuvants.

Integrated hepatitis B virus DNA maintains surface antigen production during antiviral treatment.

The focus of hepatitis B functional cure, defined as sustained loss of hepatitis B virus (HBV) surface antigen (HBsAg) and HBV DNA from blood, is on eliminating or silencing the intranuclear template for HBV replication, covalently closed circular DNA (cccDNA). However, HBsAg also derives from HBV DNA integrated into the host genome (iDNA). Little is known about the contribution of iDNA to circulating HBsAg with current therapeutics. We applied a multiplex droplet digital PCR assay to demonstrate that iDNA is responsible for maintaining HBsAg quantities in some individuals. Using paired bulk liver tissue from 16 HIV/HBV-coinfected persons on nucleos(t)ide analog (NUC) therapy, we demonstrate that people with larger HBsAg declines between biopsies derive HBsAg from cccDNA, whereas people with stable HBsAg levels derive predominantly from iDNA. We applied our assay to individual hepatocytes in paired tissues from 3 people and demonstrated that the individual with significant HBsAg decline had a commensurate loss of infected cells with transcriptionally active cccDNA, while individuals without HBsAg decline had stable or increasing numbers of cells producing HBsAg from iDNA. We demonstrate that while NUC therapy may be effective at controlling cccDNA replication and transcription, innovative treatments are required to address iDNA transcription that sustains HBsAg production.

Ultrasensitive electrochemical detection of hepatitis b virus surface antigen based on hybrid nanomaterials

This study investigates a sandwich-type electrochemical immunosensor for the determination of Hepatitis B Virus Surface Antigen (HBsAg) as the biological target. Capture antibody (Ab1) was immobilized on the synthesized magnetic nanoparticles coated with silica and APTES (MNP@SiO2@APTES). A reporter antibody (Ab2) was assembled on gold nanoparticle-Thionine (GNP), which made use of Th as a redox probe for electrochemical detection. Each gold nanoparticle holds a lot of thionine molecules on its surface. Therefore, after the formation of a sandwich-type probe a magnified electrical signal is achieved. On the other hand, a magnet has been implemented in the electrode. Thus, Magnetic nanoparticle (MNP) acts as the probe collector and fixator component on the electrode's surface, assuring a strong and prolonged interaction of the ultimate sandwich-type probe with the electrode. Under optimal conditions, the current signal increased with the increment of HBsAg concentration in the linear dynamic range of 0.001 fg/ml-2 ng/ml with a detection limit (LOD) of 0.3ag/ml (S/N = 3). Furthermore, the assembled immunosensor successfully quantified the HBsAg concentration in serum. The successful results imply the high potential of the proposed immunosensor in developing ultrasensitive and rapid diagnostic platforms.

FREQUENCY POSTIVITY OF HEPATITIS B VIRUS SURFACE ANTIGEN AND ANTI HEPATITS C VIRSUS ANTIBOIDES IN CHRONIC KIDNEY DISEASE PATIENTS ON DIALYSIS VISITING BACHA KHAN MEDICAL COMPLEX SWABI

Objective: The objective of this study was to investigate the existence percentage of hepatitis B surface antigen and anti Hepatitis C virus antibodies in chronic kidney patients on dialysis. Material &amp; Method: This was a cross-sectional study. It was conducted at Pathology Department Bacha khan Medical Complex swabi. Duration of this was six months from January 2018 to June 2018. Two hundred and forty six (246) chronic renal failure (CRF) patients who were on regular dialysis were taken for this study. Their blood samples were taken for hepatitis B virus surface antigen (HBsAg) and anti hepatitis C virus antibodies (antiHCVAb) detection. The analysis was performed by enzyme linked immunosorbent assay (ELISA) method. Results: In the results total 246 patients were enrolled in which 49(32.6%) male and 21(21.8%) were HBsAg positive and 23 (15.3%) male, 11 (11.4%) female were HCV positive. Conclusion: HBV and Anti HCV antibodies presence has been detected in chronic kidney disease (CKD) patients on dialysis. Therefore strict control measures should be taken for the control of hepatotropic infection and transmission.

Selected ginsenosides interfere efficiently with hepatitis B virus mRNA expression levels and suppress viral surface antigen secretion

Ginsenosides are a class of natural steroid glycosides and triterpene saponins found in Panax ginseng. After screening of a commercial ginsenoside compound library for low cellular cytotoxicity and the ability to mediate efficient reductions in hepatitis B virus (HBV) mRNA expression levels in HepG2.2.15 cells, three ginsenosides (Rg6, Rh4, and Rb3) are selected. Thereafter, using the same cellular model, all three ginsenosides are shown to mediate efficient, selective inhibition of HBV mRNA expression levels, and also interfere with the secretion of both HBV particles and hepatitis B surface antigen (HBsAg). Drug combination studies are performed in both HepG2.2.15 and HBV-infected HepG2-NTCPsec+ cell models with the selected ginsenosides and lamivudine (LMV), a nucleoside analogue used to treat chronic hepatitis B (CHB) infections. These studies, involving RT-qPCR and ELISA, suggest that Rh4/LMV combinations in particular act synergistically to inhibit the secretion of HBV particles and HBsAg. Therefore, on the assumption that appropriate in vivo data are in future agreement, Rh4, in particular, might be used in combination with nucleoside/nucleotide analogues (NUCs) to devise an effective, cost-efficient combination therapy for the treatment of patients with CHB infections.

Dual role of neddylation in transcription of hepatitis B virus RNAs from cccDNA and production of viral surface antigen

Background & AimsHBV persistence is maintained by both an episomal covalently closed circular (ccc)DNA reservoir and genomic integration of HBV DNA fragments. While cccDNA transcription is regulated by Cullin4A-DDB1-HBx-mediated degradation of the SMC5/6 complex, HBsAg expression from integrants is largely SMC5/6 independent. Inhibiting neddylation of Cullin-RING ubiquitin ligases impairs degradation of substrates. Herein, we show that targeting neddylation pathway components by small-interfering (si)RNAs or the drug MLN4924 (pevonedistat) suppresses expression of HBV proteins from both cccDNA and integrants.MethodsAn siRNA screen targeting secretory pathway regulators and neddylation genes was performed. Activity of MLN4924 was assessed in infection and integration models. Trans-complementation assays were used to study HBx function in cccDNA-driven expression.ResultssiRNA screening uncovered neddylation pathway components (Nedd8, Ube2m) that promote HBsAg production post-transcriptionally. Likewise, MLN4924 inhibited production of HBsAg encoded by integrants and reduced intracellular HBsAg levels, independent of HBx. MLN4924 also profoundly inhibited cccDNA transcription in three infection models. Using the HBV inducible cell line HepAD38 as a model, we verified the dual action of MLN4924 on both cccDNA and integrants with sustained suppression of HBV markers during 42 days of treatment.ConclusionsNeddylation is required both for transcription of a cccDNA reservoir and for the genomic integration of viral DNA. Therefore, blocking neddylation might offer an attractive approach towards functional cure of chronic hepatitis B.Lay summaryCurrent treatments for chronic hepatitis B are rarely able to induce a functional cure. This is partly because of the presence of a pool of circular viral DNA in the host nucleus, as well as viral DNA fragments that are integrated into the host genome. Herein, we show that a host biological pathway called neddylation could play a key role in infection and viral DNA integration. Inhibiting this pathway could hold therapeutic promise for patients with chronic hepatitis B.

Sero-prevalence of Hepatitis B virus surface antigen and associated factors among women of reproductive age in Bench Maji Zone, Southwest Ethiopia: community based cross-sectional study.

Hepatitis B virus infection is one of the leading causes of liver diseases which occurs worldwide particularly in developing countries. It is often caused by prenatal transmission from mother to child or household transmission from a close contact during early childhood. It causes different complications like; jaundice, induces premature labor, and prematurity. The aim of this study was to estimate the sero-prevalence of hepatitis B virus surface antigen and associated factors among women of reproductive age in Bench Maji Zone, South West Ethiopia. A community-based cross-sectional study was conducted from December 15th, 2016 to February 15th, 2017. Multistage sampling technique was applied to select study participants. Logistic regression analysis was applied and p-values < 0.05 was used to see the significant association between dependent and independent variables. A total of 330 participants were included in this study yielding 98.8% response rate. The sero-prevalence of HBsAg among women of reproductive age was 28(8.5%). Having multiple sexual partners (AOR = 18.73, 95% CI =3.65, 96.21) history of unprotected sex (AOR = 9.39, 95% CI =1.64, 53.77) were found to be significantly associated with sero-prevalence of HBV. The sero-prevalence of HBV infection among women of reproductive age was highly endemic. Hence, behavioral education and communication programs focusing on reduction of risky sexual behaviors should be designed to reduce HBV infection.

Correlation between Results of Semi-Quantitative and Quantitative Tests for Hepatitis B Virus Surface Antigen among Patients Achieving Viral Suppression with Antiviral Treatment.

Background: Hepatitis B virus (HBV) infection remains a threat to global public health. Serum hepatitis B surface antigen (HBsAg) has been used in screening for HBV infection. Quantitative HBsAg assays are useful for monitoring the natural history of HBV infection and its response to therapy. The aim of this study was to determine the relationship between quantitative (qHBsAg; IU/mL) and semi-quantitative (sqHBsAg; signal-to-cutoff ratio [S/Co]) HBsAg titers in patients with chronic hepatitis B (CHB). Methods: We retrospectively included 284 samples with HBV DNA < 20 IU/mL from patients who had simultaneous qHBsAg (using electrochemiluminescence assay) and sqHBsAg tests. Patients were grouped according to their serum HBV-envelope antigen (HBeAg) status (HBeAg-negative, n = 239 and HBeAg-positive, n = 45). The Spearman test was used to analyze the correlation between the quantitative and semi-quantitative assays. Results: There was a significant linear correlation between sqHBsAg and qHBsAg in the HBeAg-negative patients (qHBsAg [IU/mL] = 0.0094 × sqHBsAg [S/Co]1.323; adjusted R2 = 0.8445; p < 0.001). There was a substantial hook effect in the assays from the HBeAg-positive patients, so we performed a stratified analysis according to qHBsAg <1000 IU/mL or ≥1000 IU/mL and found a significant positive linear correlation between sqHBsAg S/Co and qHBsAg (qHBsAg [IU/mL] = 0.072 × sqHBsAg [S/Co]1.331; adjusted R2 = 0.7878; p < 0.001) in HBeAg-positive patients with qHBsAg titers of <1000 IU/mL and a significant negative correlation in HBeAg-positive patients with qHBsAg titers of ≥1000 IU/mL (qHBsAg [IU/mL] = 8.987 × 1014 × sqHBsAg [S/Co]−3.175; adjusted R2 = 0.6350; p < 0.001). Conclusions: There was a highly linear, positive correlation between qHBsAg and sqHBsAg in HBeAg-negative CHB patients. The hook effect led to a negative correlation in HBeAg-positive CHB patients with qHBsAg titers ≥1000 IU/mL.

Modelling the prevalence of hepatitis B towards eliminating it as a major public health threat in China

BackgroundThe World Health Organization (WHO) requires reduction in the prevalence of hepatitis B virus (HBV) surface antigen (HBsAg) in children to 0.1% by 2030, a key indicator for eliminating viral hepatitis as a major public health threat. Whether and how China can achieve this target remains unknown, although great achievements have been made. We aimed to predict the decline of HBsAg prevalence in China and identify key developments needed to achieve the target.MethodsAn age- and time-dependent dynamic compartmental model was constructed based on the natural history of HBV infection and the national history and current status of hepatitis B control. The model was run from 2006 to 2040 to predict the decline of HBsAg prevalence under three scenarios including maintaining current interventions (status quo), status quo + peripartum antiviral prophylaxis (PAP, recommended by WHO in 2020), and scaling up current interventions + PAP.ResultsUnder the status quo, HBsAg prevalence would decrease steadily in all age groups, but the WHO’s target of 0.1% prevalence in children aged < 5 years would not be achieved until 2037. The results are robust according to sensitivity analyses. Under the status quo + PAP, the HBsAg prevalence of children aged < 5 years would significantly decrease with the introduction of PAP, and the higher the successful interruption coverage is achieved by PAP, the more significant the decline. However, even if the successful interruption coverage reaches 90% by 2030, the 0.1% prevalence target would not be met until 2031. Under the scaling up current interventions + PAP, combined with scale-up of current interventions, the WHO’s 0.1% target would be achieved on time or one year in advance if PAP is introduced and the successful interruption coverage is scaled up to 80% or 90% by 2030, respectively.ConclusionsIt is difficult for China to achieve the WHO’s target of 0.1% HBsAg prevalence in children by 2030 by maintaining current interventions. PAP may play an important role to shorten the time to achieve the target. A comprehensive scale-up of available interventions including PAP will ensure that China achieves the target on schedule.

Demonstration of durable hepatitis B immune memory in children vaccinated with a DTaP5-IPV-HepB-Hib infant-toddler series 7 to 8 years previously

ABSTRACT Vaccination against hepatitis B (HepB) provides long-term protection against infection. This is despite a reduction in HepB surface antibody (anti-HBs) concentrations over time to levels below the well-accepted correlate of protection of ≥10 mIU/mL. Continued evidence of immune memory and protection despite declined anti-HBs concentrations can be demonstrated by HepB virus surface antigen challenge studies. Long-term immune memory and protection against HepB infection has not been demonstrated previously for the pediatric hexavalent vaccine DTaP5-IPV-HepB-Hib. This phase 3, multicenter, single-group, open-label challenge study (NCT04490499; EudraCT: 2020–000126–26) evaluated immune memory against HepB infection in children who had received DTaP5-IPV-HepB-Hib at 2, 4, and 11–12 months of age, or at 2, 3, 4, and 12 months of age. At age 8–9 years, they were each challenged with 5 μg of monovalent HepB vaccine. Anti-HBs levels were measured on pre-challenge day 1 and post-challenge day 30. At baseline, 45.4% (93 of 205) had anti-HBs levels ≥10 mIU/mL. On post-challenge day 30, 99.5% (201 of 202) had anti-HBs levels ≥10 mIU/mL, regardless of initial vaccination schedule. Post-challenge, geometric mean concentrations increased 71-fold over baseline and 96.0% of children had a ≥4-fold rise in anti-HBs concentrations with similar results across both dosing schedules. The challenge dose was well tolerated. The robust anti-HBs responses after a single 5-μg dose of HepB vaccine confirm the persistence of a HepB immune memory and demonstrate that DTaP5-IPV-HepB-Hib provides long-term protection against HepB.

Scorpion venom exhibits adjuvant effect by eliciting HBsAg-specific Th1 immunity through neuro-endocrine interactions

The Hottentotta rugiscutis scorpion venom (Hrv) contains neurotoxins, which elicit a strong innate immune response through the activation of the Hypothalamus-pituitary-adrenal axis, which could improve the quality of adaptive immunity. Hence, the Hrv was used as an adjuvant for the Hepatitis-B virus surface antigen (HBsAg) and assessed its ability in the activation of innate (NGF, CORT, cellularity, NO) and adaptive (IgM, IgG, IgG1/IgG2a/IgG2b/IgG3, Th1/Th2 cytokines, avidity) immunity. Here, the Hrv and HBsAg were given in the mixed form (HBsAg-Hrv) as well as in a separate form (HBsAg+Hrv). The NGF levels in plasma/spleen and CORT in plasma were found to be elevated optimally at 5 h and 6 h post-Hrv injection, respectively. Further studies showed that CORT and NGF levels were also highly upregulated in the HBsAg-Hrv group. The HBsAg-specific IgM titer was found to be increased in the HBsAg+Hrv group and total IgG was relatively similar among alum and Hrv-test groups, but IgG2a/IgG2b/IgG3 levels were higher along with IL-1β in HBsAg-Hrv groups. The study showed that the venom from H. rugiscutis acts as a vaccine adjuvant for HBsAg to develop strong antigen-specific Th1 immunity. The Hrv also enhances the antibody-avidity which may improve the neutralizing ability of antibodies with systemic infectious agents. The study also elucidated that the venom acts by neuroendocrine-immune mechanism and majorly impacts splenocytes through NGF and corticosterone.