Envelope Antigen Research Articles

Hepatitis B Core-Related Antigen is a Biomarker for off-Treatment Relapse After Long-Term Nucleos(t)ide Analog Therapy in Patients with Chronic Hepatitis B.

ObjectiveIt remains unknown how to stratify the risk of clinical relapse of chronic hepatitis B (CHB) patients after stopping nucleos(t)ide analogs (NAs) antiviral therapy.MethodsThe current post hoc analysis included 122 non-cirrhotic patients with chronic hepatitis B virus infection who were positive for hepatitis B envelope antigen (HBeAg) and discontinued long-term NA therapy after achieving HBeAg seroconversion for a median of 2.5 years. Post hoc analysis of end-of-treatment (EOT) hepatitis B core-related antigen (HBcrAg) levels was performed using a chemiluminescent enzyme immunoassay.ResultsA total of 78/122 (63.9%) patients experienced sustained response after NAs cessation, and 44/122 (36.1%) patients experienced clinical relapse. In multivariate analysis, EOT HBcrAg (hazard ratio [HR] = 2.105 95% CI: 1.440–3.077, p < 0.001), hepatitis B surface antigen (HBsAg) ≥100 IU/mL (HR = 4.406, 95% CI 1.567–12.389, p = 0.005) and age (HR = 1.051, 95% CI: 1.010–1.093, p = 0.049) were independently associated with clinical relapse. A cut-off value of 4.0 log10 U/mL of HBcrAg was defined by maximized Youden’s index. An EOT HBcrAg level of ≥4.0 log10 U/mL was associated with higher risks of clinical relapse (65.8% vs 23.2%, p<0.001) and HBeAg reversion (27.5% vs 1.6%, p < 0.001). In majority of patients (n = 91) who had a high EOT HBsAg level (≥100 IU/mL), serum HBcrAg level could further discriminate patients at low risk of clinical relapse. Patients with an HBcrAg level ≥4.0 log10 U/mL had significantly higher cumulative incidence rates of clinical relapse (78.1% vs 29.4%, p < 0.001) and HBeAg reversion (29.4% vs 0%, p < 0.001).ConclusionSerum EOT HBcrAg level can be a predictor of off-treatment relapse in patients with CHB. An HBcrAg level of 4.0 log10 U/mL may identify patients at high risk of clinical relapse after treatment cessation.

HIV envelope antigen valency on peptide nanofibers modulates antibody magnitude and binding breadth

A major challenge in developing an effective vaccine against HIV-1 is the genetic diversity of its viral envelope. Because of the broad range of sequences exhibited by HIV-1 strains, protective antibodies must be able to bind and neutralize a widely mutated viral envelope protein. No vaccine has yet been designed which induces broadly neutralizing or protective immune responses against HIV in humans. Nanomaterial-based vaccines have shown the ability to generate antibody and cellular immune responses of increased breadth and neutralization potency. Thus, we have developed supramolecular nanofiber-based immunogens bearing the HIV gp120 envelope glycoprotein. These immunogens generated antibody responses that had increased magnitude and binding breadth compared to soluble gp120. By varying gp120 density on nanofibers, we determined that increased antigen valency was associated with increased antibody magnitude and germinal center responses. This study presents a proof-of-concept for a nanofiber vaccine platform generating broad, high binding antibody responses against the HIV-1 envelope glycoprotein.

Hepatitis B Envelope Antigen in Children and Adults with Hepatitis B Infection in Tertiary Health Facility in North East Nigeria During the Period 2000-2015

Introduction: Worldwide, most people living with chronic HBV infection are in in low- and middle-income countries. Most of the burden of disease from HBV infection comes from infections acquired before the age of 5 years. Materials and Methods: Records of Hepatitis B surface and envelope antigen results of children and adults in Federal Teaching Hospital, Gombe between May 2000 and May 2015 were analyzed Results: 22,862 individuals were tested for Hepatitis B surface antigen. 19.5% (4456) tested positive. 24.7 % (3146) and 12.9% (1310) of males and females respectively were HBsAg positive. HBsAg Peak prevalence of 21.8% was in the age group 26-46 (2533) and the lowest prevalence in infancy (3.5%). Amongst males, the 19-25year age group had the peak prevalence of 28.6% and in females the age group 5-9 years constituted the highest (20.3%). 36% (1602/4456) of HBsAg positive children and adults were tested for HBeAg. 26.2% (420/1602) of individuals with HBsAg carriage were HBeAg. More males (307/1105) than females (113/495) were HBeAg positive but not statistically significant. (P=0.034). Prevalence of HBeAg was highest in infants (50%) and children 1-4 years (50%) age group and thereafter declined with increasing age. Females of the younger age group &lt;1year, 1-4 years and 5-9 years and older age group, 56-65 and &gt;65 years, compared to their male carriers of HBsAg had higher prevalence of HBeAg but these were not statistically significant. Conclusion: A fifth of HBsAg carriers were HBeAg positive and HBeAg positivity decreased with increasing age. Hepatitis B vaccination in Nigeria requires urgent strengthening. Keywords: Hepatitis, HBsAg, HBeAg Children, Adults, Nigeria.

Inflammatory Response, Plasma Albumin, Creatinine, Alanine Aminotransferase, and Packed Cell Volume in Relationship with the Degree of Anemia and Gestational Age in HbAA Anemic Pregnant Women

Background: Anemia in pregnancy which may be mild, moderate, or severe is a common physiological disorder that can lead to poor pregnancy outcome which may be primary or secondary to problems associated with hepatic, renal, and immune system which may be indicated by alterations in packed cell volume (PCV), alanine transaminase, albumin, tumor necrosis factor-alpha (TNF-α), and creatinine. This work is, therefore, designed to determine inflammatory response, plasma albumin, creatinine, alanine aminotransferase (ALT), and PCV in relationship with the degree of anemia and gestational age in anemic pregnant women. Methods: Two hundred (200) HbAA anemic pregnant women and 100 nonanemic pregnant women were recruited as test and control subjects, respectively. All subjects were negative to HIV-Ag-Ab, acid-fast bacillus (AFB)-Ziehl–Neelsen, Plasmodium, anti-hepatitis C virus (HCV), and hepatitis B envelope antigen (HBeAg) tests. HIV-Ag-Ab, TNF-α, anti-HCV, and HBeAg were determined by enzyme-linked immunosorbent assay; AFB by Ziehl–Neelsen staining; Plasmodium by thick-film Giemsa staining; hemoglobin types by hemoglobin electrophoresis; albumin, creatinine, and ALT by auto-chemistry analysis using COBAS C11; and PCV by microhematocrit tube method. Results: Eighteen percent (36) of the anemic pregnant women had severe anemia whereas 82% (164) had moderate anemia. The results obtained showed a significant increase in the plasma value of TNF-α and a decrease in the PCV in anemic pregnant women compared with the results obtained in the nonanemic pregnant women (P &lt; 0.05). There was a significant increase in plasma TNF-α in severe anemia compared with the anemic pregnant women with moderate anemia (P &lt; 0.05). Conclusions: This work revealed a significant increase in plasma TNF-α and a decrease in PCV in anemic pregnant women which was more intense in anemic pregnant women with severe anemia while the pattern of anemia showed that 18% (36) of the anemic pregnant women had severe anemia whereas 82% (164) had moderate anemia.

Laboratory healthcare gap of hepatitis B care in Yogyakarta, Indonesia

Serological markers of hepatitis B virus (HBV) infection (HBsAg, anti-HBs, hepatitis B envelope antigen [HBeAg], anti-HBe, and anti-hepatitis B core [HBc] IgM/IgG) was used as the basis for diagnosis and differences in the chronicity of hepatitis B infection. This study aims to explore the laboratory healthcare gap of the patient with hepatitis B infection in our setting and whether laboratory data completeness affects the results. This study used retrospective data taken from the Medical Records of hepatitis B patients at Dr. Sardijto Hospital in 2020. The subjects in this study were hepatitis B patients with positive HBsAg. The exclusion criteria were individuals who had co-infection with the hepatotropic virus or HIV. This study was funded by Deputi Bidang Penguatan Riset dan Pengembangan, Kementerian Riset dan Teknologi/Badan Inovasi Nasional. A total of 232 patients were included in the study. All patients underwent HBsAg examination and tested positive, with 65.09% of subjects had HBV DNA examination. HBeAg examination result was only found in 18% of patients. Anti HBc examinations were only found in 2 patients. No subjects were examined for anti-HBs in this study. The proportion of subjects examined for the liver function was still low (< 50%), with the most widely checked parameters are AST and ALT while other parameters are very rare. The utilization of serological tests and hepatic function in hepatitis B patients in Yogyakarta, Indonesia is still low. Intervention and financial support are needed to improve the quality of life of patients with hepatitis B who were treated.

Application of Risk Scores for Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: Current Status and Future Perspective.

Accurate risk prediction for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) may guide treatment strategies including initiation of antiviral therapy and also inform implementation of HCC surveillance. There have been 26 risk scores developed to predict HCC in CHB patients with (n = 14) or without (n = 12) receiving antiviral treatment; all of them invariably include age in the scoring formula. Virological biomarkers of replicative activities (i.e., hepatitis B virus DNA level or hepatitis B envelope antigen status) are frequently included in the scores derived from patients with untreated CHB, whereas measurements that gauge severity of liver fibrosis and/or reserve of hepatic function (i.e., cirrhosis diagnosis, liver stiffness measurement, platelet count, or albumin) are essential components in the scores developed from treated patients. External validation is a prerequisite for clinical application but not yet performed for all scores. For the future, higher predictive accuracy may be achieved with machine learning based on more comprehensive data.

Prospective Artificial Intelligence to Dissect the Dengue Immune Response and Discover Therapeutics.

Dengue virus (DENV) poses a serious threat to global health as the causative agent of dengue fever. The virus is endemic in more than 128 countries resulting in approximately 390 million infection cases each year. Currently, there is no approved therapeutic for treatment nor a fully efficacious vaccine. The development of therapeutics is confounded and hampered by the complexity of the immune response to DENV, in particular to sequential infection with different DENV serotypes (DENV1–5). Researchers have shown that the DENV envelope (E) antigen is primarily responsible for the interaction and subsequent invasion of host cells for all serotypes and can elicit neutralizing antibodies in humans. The advent of high-throughput sequencing and the rapid advancements in computational analysis of complex data, has provided tools for the deconvolution of the DENV immune response. Several types of complex statistical analyses, machine learning models and complex visualizations can be applied to begin answering questions about the B- and T-cell immune responses to multiple infections, antibody-dependent enhancement, identification of novel therapeutics and advance vaccine research.

Development of Zika NS1 ELISA methodology for seroprevalence detection in a cohort of Mexican patients in an endemic region

BackgroundZika (ZIKV) is a mosquito-borne virus that has caused multiple outbreaks in Americas. The early and accurate diagnosis of ZIKV is the key to minimize the health burden imposed on the infected patients. Many commercial ZIKV diagnosis kit are available based on ZIKV envelope antigen with varying sensitivity and specificity. ObjectiveThe aim of this study was to develop sensitive ELISA methodology based on recombinant ZIKV NS1 and NS1 β-ladder antigens for seroprevalence detection in a cohort of patients in an arbovirus endemic Mexican region in comparison to a commercial kit. Study designWe obtained serum samples from 60 patients presenting with febrile illness and from 10 healthy donors in Michoacán state in 2016–2017. These samples were screened for ZIKV by RT-PCR and used to develop NS1 based ELISA and compared to a commercial kit. ResultsOur results indicate that both ZIKV sNS1 and β-ladder-based ELISA can reliably detect anti-ZIKV NS1 antibodies in infected patients, relevant for the serodiagnosis of ZIKV. Determination of antibody titers showed that it offered higher sensitivity than a commercially available ZIKV ELISA. Over 90% seropositivity against ZIKV for the febrile patients was detected in Lázaro Cárdenas which is an arbovirus endemic region while lower seropositivity was observed in the healthy volunteers in Morelia (non-endemic area). ConclusionWe conclude that our simple and sensitive in-house NS1 based ELISA used in this study has excellent sensitivity, is easy to use and can provide fast results suitable for larger population-based seroprevalence studies in the future.

Thyroid dysfunction is associated with the loss of hepatitis B surface antigen in patients with chronic hepatitis B undergoing treatment with α-interferon.

ObjectiveTo investigate the influence of thyroid dysfunction on the antiviral efficacy of α-interferon in adult patients with chronic hepatitis B (CHB).MethodsWe performed a retrospective study of 342 patients with CHB who underwent interferon treatment for >12 weeks. Patients with thyroid dysfunction before or during treatment were defined as the thyroid dysfunction group (n = 141) and those with normal thyroid function were defined as the normal thyroid function group (n = 201). The prevalences of hepatitis B virus (HBV) DNA undetectability, low hepatitis B surface antigen (HBsAg) titre (<250 IU/mL), HBsAg loss, and hepatitis B envelope antigen loss were compared.ResultsDuring interferon treatment, 69 of 270 (25.6%) participants with normal thyroid function at baseline developed thyroid dysfunction, whereas 11 of 72 (15.3%) with thyroid dysfunction at baseline regained normal thyroid function. The thyroid dysfunction group had significantly higher prevalences of low HBsAg titre (29.8% vs. 18.9%) and HBV DNA undetectability (66.0% vs. 40.3%). Multivariate logistic regression analysis showed that thyroid dysfunction was associated with HBsAg loss (odds ratio 4.945, 95% confidence interval 1.325–18.462).ConclusionsThese results suggest that thyroid dysfunction is not an absolute contraindication, but is associated with HBsAg loss, in patients with CHB undergoing α-interferon treatment.

Temperature-dependent secretion of Zika virus envelope and non-structural protein 1 in mammalian cells for clinical applications

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus associated with congenital Zika syndrome and Guillain-Barré syndrome in adults. The recombinant ZIKV envelope (E) antigen can be useful for serodiagnosis of ZIKV infection and for monitoring immune responses during preclinical and clinical ZIKV vaccine development. In this study, we describe production of ZIKV E using the modified polyethyleneimine (PEI) transfection in HEK293 cells to improve cost-effective large-scale production. We show that the secretion of ZIKV E in HEK293 cells is dependent on cell culture incubation temperatures where incubation at a low temperature of 28 °C improved protein secretion of both, E-CD4 and E, whereas a substantial decrease in secretion was observed at 37 °C. The resulting E-CD4 produced at low temperature yielded similar binding profiles in ELISAs in comparison with a commercially available E protein using human seropositive sera to ZIKV. We also show that ZIKV NS1 and NS1 β-ladder antigens produced in HEK293 cells, have similar binding profiles in ELISA which suggests that both NS1 or NS1 β-ladder can be used for serodiagnosis of ZIKV. In conclusion, we propose a cost-effective production of the ZIKV E and NS1, suitable for both, clinical and research applications in endemic countries.

Immunoprofiling Correlates of Protection Against SHIV Infection in Adjuvanted HIV-1 Pox-Protein Vaccinated Rhesus Macaques.

Human immunodeficiency virus type 1 (HIV-1) infection remains a major public health threat due to its incurable nature and the lack of a highly efficacious vaccine. The RV144 vaccine trial is the only clinical study to date that demonstrated significant but modest decrease in HIV infection risk. To improve HIV-1 vaccine immunogenicity and efficacy, we recently evaluated pox-protein vaccination using a next generation liposome-based adjuvant, Army Liposomal Formulation adsorbed to aluminum (ALFA), in rhesus monkeys and observed 90% efficacy against limiting dose mucosal SHIV challenge in male animals. Here, we analyzed binding antibody responses, as assessed by Fc array profiling using a broad range of HIV-1 envelope antigens and Fc features, to explore the mechanisms of ALFA-mediated protection by employing machine learning and Cox proportional hazards regression analyses. We found that Fcγ receptor 2a-related binding antibody responses were augmented by ALFA relative to aluminium hydroxide, and these responses were associated with reduced risk of infection in male animals. Our results highlight the application of systems serology to provide mechanistic insights to vaccine-elicited protection and support evidence that antibody effector responses protect against HIV-1 infection.

Frequency of Hepatitis B Virus Envelope Antigen and Antibodies Among Chronic Carriers in Ibadan, Nigeria.

Hepatitis B virus (HBV) infection is a major health challenge in sub-Saharan Africa with a prevalence rate of >7%. It is an important clinical problem due to its potential adverse sequelae, including hepatocellular carcinoma. The additional challenge of its associated chronic infection makes its prevention difficult despite the widely available vaccine. Infectious chronic HBV carriers are likely to be the most common source of HBV infection in the community. This study aims to study the degree of infectiousness of HBV carriers by testing for HBV envelope antigen (HBeAg) and antibody among HBV carriers attending the gastrointestinal clinic at University College Hospital (UCH, Ibadan, Nigeria). This is a cross-sectional study among 129 consecutively recruited HBV infected individuals who gave informed consent to participate in the study. The participants of the study were recruited from clients attending the gastrointestinal clinic of UCH. The sera obtained from the participants were tested for HBsAg, HBeAg, and antibodies to HBV envelope antibodies (HBeAb) using commercially available enzyme-linked immunosorbent assay (ELISA) test kits by DIA.PRO (Diagnostic Bioprobes Srl, Milan, Italy) according to the manufacturer's instruction. Of 129 samples collected, 63 (48.8%) tested positive for HBeAg, whereas 72 (55.8%) tested positive for HBeAb (p = 0.012); HBeAg prevalence was higher in females than males and also prevalent among the age group of 31-40 years. Seventy-four (57.4%) of the participants also tested positive for both HBeAg and HBeAb, whereas 55 (42.6%) were negative for both. This study shows that there is a high level of infectiousness among HBsAg-positive individuals in Ibadan, Nigeria.

Transforming growth factor β as a possible independent factor in chronic hepatitis B.

To investigate the association between immune-cell-related cytokines and the development of chronic hepatitis B (CHB), patients with chronic hepatitis B virus (HBV) infection in the immunotolerant (IT) phase (n = 30) or hepatitis B envelope antigen (HBeAg)-positive CHB (n = 250) were enrolled in this study. Serological indicators and plasma cytokine levels were measured at the time of enrollment. The results showed that there were significant differences in the median age of the patients (27 vs. 31 years), alanine aminotransferase levels (ALT, 29.85 vs. 234.70 U/L), alanine aminotransferase levels (AST, 23.40 vs. 114.90 U/L), HBsAg levels (4.79 vs. 3.88 log10 IU/ml), HBeAg levels (1606.36 vs. 862.47 S/CO), and the HBV DNA load (8.17 vs. 6.71 log10 IU/ml) between the IT and CHB groups (all P < 0.01). The median values of Fms-like tyrosine kinase 3 ligand (FLT3-L), interferon-gamma (IFN-γ), interleukin- 17A (IL-17A), and transforming growth factor beta (TGF-β1) were significantly higher in the IT group than in the CHB group (FLT3-L, 41.62 vs. 27.47 pg/ml; IFN-γ, 42.48 vs. 33.18 pg/ml; IL-17A, 15.66 vs. 8.90 pg/ml; TGF-β1, 4921.50 vs. 2234 pg/ml; all P < 0.01). The median IFN-α2, TGF-β3 and IL-10 levels in the IT group were significantly lower than those in the CHB group (IFN-α2, 15.24 vs. 35.78 pg/ml, P = 0.000; TGF-β3, 131.69 vs. 162.61 pg/ml, P = 0.025; IL-10, 5.02 vs. 7.9 pg/ml, P = 0.012). Multivariate logistic regression analysis indicated that TGF-β 1 (OR = 0.999, 95% CI 0.999-1.000, P < 0.001) and TGF-β2 levels (OR = 1.008, 95%CI 1.004-1.012, P < 0.001) were modestly but significantly associated with the incidence of CHB. The results suggest that TGF-β level might be an independent factor related to the occurrence of CHB.

Broadly neutralizing HIV-1 antibody reactivity in HIV tests: implications for diagnostics.

Passive immunization with broadly neutralizing antibodies (bNAbs) is under evaluation for HIV prevention. BNAbs target gp120 or gp41, two HIV envelope antigens commonly present in diagnostic tests. Depending on bNAb type and dose administered to humans, serum levels can reach nearly 1 mg/ml and wane over several weeks to months. We investigated the reactivity of bNAbs in HIV serological tests to inform diagnostic testing practices for persons treated with these products. The antigp120 bNAbs VRCO1, PGT121, PGT145, 3BNC117, 10-1074 and N6 and antigp41 bNAbs 10E8 and 10E8v4 were tested with the laboratory-based Bio-Rad Ag/Ab Combo assay, the point-of-care single-use Determine Combo, OraQuick, Reveal G4, SureCheck, Uni-Gold, INSTI and DPP HIV-1/2 assays, and the supplemental Geenius and HIV-1 Western Blot assays. At 1 mg/ml, all bNAbs were nonreactive in four screening tests. OraQuick, SureCheck, Reveal G4 and INSTI detected at least two bNAbs each; SureCheck exhibited reactivity to six bNAbs. Geenius was HIV-1 indeterminate (gp160+) with all bNAbs except PGT121, which was HIV antibody-negative. HIV-1 Western Blot was indeterminate (gp41+/gp160+) with 10E8 and 10E8v4 and negative with the remaining bNAbs. There was no correlation between the test antigen construct(s) and bNAb reactivity. We identified a laboratory-based Ag/Ab EIA and three single-use rapid HIV tests that are nonreactive against a panel of bNAbs supporting some diagnostic tests can distinguish HIV-1 infection events among persons receiving bNAb immunoprophylaxis. Evaluation of HIV diagnostic tests prior to clinical use may identify suitable serologic assays for persons administered bNAbs.

Molecular characterization of hepatitis B virus basal core promoter and precore region of isolates from chronic hepatitis B patients.

To analyse mutations in precore and core promoter regions of hepatitis B virus genome in chronic hepatitis B patients. The cross-sectional prospective study was conducted at the Centre of Biotechnology and Microbiology, University of Peshawar and Pakistan Health Research Council (PHRC), Research Centre, Khyber Medical College Peshawar from June 2014 to June 2015, and comprised samples from treatment-naïve chronic hepatitis B patients aged >15 years from three cities of Pakistan. The samples included patients who were both positive and negative for hepatitis B envelope antigen. Viral load, hepatitis B envelope antigen / anti-hepatitis B envelope status, hepatitis B virus enzyme-linked immunosorbent assay and alanine aminotransferase levels were determined. Direct sequencing of basal core promoter and precore regions of hepatitis B virus genome was carried out following a nested polymerase chain reaction approach. Phylogenetic tree was constructed using Molecular Evolutionary Genetics Analysis software version 6.0. Data was analysed using SPSS 16. Of the 50 patients, 33(66%) were males. The overall mean age was 28.5±11.4 years. Of all the subjects, 25(50%) each were positive and negative for hepatitis B envelope antigen. Precore stop codon mutation G1896A was detected in 19 (38%) isolates; 17(34%) among negative patients and 2(4%) in positive patients. Classic A1762T/G1764A double mutation was noted in 15(30%) isolates. Mutation at position 1764 was observed in 12(48%) samples. A rare G1764T mutation was also detected in 6(12%) isolates. The CG1802-1803 mutation was detected in 47(94%) isolates, while all the 50(100%) isolates had T1858A. The GCAC Kozak sequence was present in 43(86%) isolates; CAA1817-1819 in 49(98%); and G1888 in 49(98%). Overall, 9(18%) isolates had wild-type sequences at all important loci, including positions 1762, 1764 and 1896. The pattern of sequences at genotype specific positions and phylogenetic tree speculates that majority of study isolates belonged to genotype D. Basal core promoter and precore regions variants along with the preponderances of genotype D-specific mutations suggested a higher risk of hepatocellular carcinoma and poor clinical outcome in such patients.

Natural History of Chronic Hepatitis B Infection Among Chinese Children and Young Adults: A Single-Center Experience.

There are limited data on the natural history of chronic hepatitis B virus (HBV) infection in Asian American children. The aim of the present study was to describe a single-center experience of chronic HBV infection in Chinese American patients in New York City. A retrospective chart review was conducted for patients with chronic HBV infection who had pediatric visits from 2006 to 2017. Clinical and laboratory data were collected to characterize the status of HBV infection and its disease course both cross-sectionally and longitudinally. Available maternal charts were reviewed. Of the total 353 patients, 72 patients (20%) were US-born. Positive hepatitis B envelope antigen (HBeAg) was documented in 208 patients (58%). Three phases of chronic HBV infection were categorized for 329 patients: immune-tolerant 112 (34%), HBeAg-positive immune-active 47 (14%), and inactive carrier 82 (25%). The remaining 88 patients (27%) did not fit into a particular category with 26 of 88 patients meeting the criteria for inactive carrier except for mildly elevated alanine aminotransferase. Age and liver enzyme levels were significantly different between HBeAg-positive and HBeAg-negative groups (P < 0.05). Among 179 patients followed for ≥5 years, the spontaneous seroconversion rate was 38%. In eight patients with linked maternal data, all children completed the HBV vaccine series and seven of eight received hepatitis B immunoglobulin. All mothers were HBeAg-positive with high HBV DNA and had no anti-viral therapy during pregnancy. Both immune-tolerant and inactive carrier phases were common for chronic HBV infection with a spontaneous seroconversion rate of 38%. All US-born patients were born in the era of implemented universal immune-prophylaxis.

Modified Adenovirus Prime-Protein Boost Clade C HIV Vaccine Strategy Results in Reduced Viral DNA in Blood and Tissues Following Tier 2 SHIV Challenge.

Designing immunogens and improving delivery methods eliciting protective immunity is a paramount goal of HIV vaccine development. A comparative vaccine challenge study was performed in rhesus macaques using clade C HIV Envelope (Env) and SIV Gag antigens. One group was vaccinated using co-immunization with DNA Gag and Env expression plasmids cloned from a single timepoint and trimeric Env gp140 glycoprotein from one of these clones (DNA+Protein). The other group was a prime-boost regimen composed of two replicating simian (SAd7) adenovirus-vectored vaccines expressing Gag and one Env clone from the same timepoint as the DNA+Protein group paired with the same Env gp140 trimer (SAd7+Protein). The env genes were isolated from a single pre-peak neutralization timepoint approximately 1 year post infection in CAP257, an individual with a high degree of neutralization breadth. Both DNA+Protein and SAd7+Protein vaccine strategies elicited significant Env-specific T cell responses, lesser Gag-specific responses, and moderate frequencies of Env-specific TFH cells. Both vaccine modalities readily elicited systemic and mucosal Env-specific IgG but not IgA. There was a higher frequency and magnitude of ADCC activity in the SAd7+Protein than the DNA+Protein arm. All macaques developed moderate Tier 1 heterologous neutralizing antibodies, while neutralization of Tier 1B or Tier 2 viruses was sporadic and found primarily in macaques in the SAd7+Protein group. Neither vaccine approach provided significant protection from viral acquisition against repeated titered mucosal challenges with a heterologous Tier 2 clade C SHIV. However, lymphoid and gut tissues collected at necropsy showed that animals in both vaccine groups each had significantly lower copies of viral DNA in individual tissues compared to levels in controls. In the SAd7+Protein-vaccinated macaques, total and peak PBMC viral DNA were significantly lower compared with controls. Taken together, this heterologous Tier 2 SHIV challenge study shows that combination vaccination with SAd7+Protein was superior to combination DNA+Protein in reducing viral seeding in tissues in the absence of protection from infection, thus emphasizing the priming role of replication-competent SAd7 vector. Despite the absence of correlates of protection, because antibody responses were significantly higher in this vaccine group, we hypothesize that vaccine-elicited antibodies contribute to limiting tissue viral seeding.

Serological detection of hepatitis B and D virus co-infection among patients attending a tertiary health facility at Maiduguri, Nigeria

BackgroundHepatitis D virus (HDV) is highly pathogenic, and clinical studies revealed that HDV infection aggravates the natural history of the underlying hepatitis B virus (HBV) infection by progression to cirrhosis that leads to early decompensation of liver function compared with HBV mono-infection. To determine the seroprevalence of HDV among HBsAg-seropositive patients and associated biochemical profiles at Maiduguri, Nigeria, a hospital-based cross-sectional study on 180 sera of patients positive for HBsAg by ELISA were evaluated for anti-HDV, hepatitis B envelop antigen, anti-HBs antibodies and liver enzyme profiles.ResultsHDV seroprevalence of 3.3% among 180 HBsAg-positive patients. Relatively higher seroprevalence of HDV was observed in males (4.3%) than in females (2.3%). The highest infection rate (20%) was obtained in patients ≥ 56 years. However, no significant association between positive anti-HDV seroprevalence and gender (p > 0.05). Of the 6 (3.3%) anti-HDV-positive patients, only 1 (16.7%) was positive for HBeAg while all were negative for anti-HBs antibodies. The mean level of liver enzyme level of AST and ALT of the anti-HDV-positive patients significantly differ from that of HBsAg mono-infected patients (p ˂ 0.05). However, no significant difference (p < 0.05) between the mean levels of liver enzymes of ALP in anti-HDV-positive and HBsAg mono-infected patients (p ˃ 0.05) was found.ConclusionThis study revealed a relatively low presence of HDV in HBsAg-positive patients. Furthermore, HDV-HBV co-infected patients had somewhat worse liver enzyme upregulation. This underscores the need for rapid HDV testing and treatment in HBV-infected patients.

The Difference of Hypoxic Inducible Factor-1α, Vascular Endothelial Growth Factor, and Transforming Growth Factor-β1 Based on Liver Fibrosis Severity in Patients with Chronic Hepatitis B

BACKGROUND: Hepatitis B is a global health problem. The disease damages hepatocytes and creates tissue hypoxic condition. Hypoxia triggers production of several mediators such as hypoxic inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-β1. The mediators act in liver fibrosis and cirrhosis, and hepatocellular carcinoma.&#x0D; AIM: The objective of the study was to determine the difference in serum HIF-1α, VEGF, and TGF-β1 levels based on liver fibrosis severity in patients with chronic hepatitis B.&#x0D; MATERIALS AND METHODS: This cross-sectional study was performed in Haji Adam Malik Hospital Medan, Indonesia, from January to July 2020. Subjects were chronic hepatitis B patients aged 18 years or older. Exclusion criteria were other chronic diseases, malignancies, or pregnancy. Liver fibrosis was determined using shear wave elastography and categorized as follow: F1, F2, F3, and F4. Serum HIF-1α, VEGF, and TGF-β1 levels were measured using enzyme-linked immunosorbent assay. Specimens were obtained from venous blood.&#x0D; RESULTS: A total of 63 patients were enrolled in this study with mean age of 40.3 (SD 11.69) years. Subjects were dominated by males (58.7%). There were no differences in serum HIF-1α, VEGF, and TGF-β1 levels based on liver fibrosis grading and also based on hepatitis B envelope antigen (HBeAg) status and gender. Associations between liver fibrosis grading, HBeAg, and gender were absent. There was a positive correlation between liver fibrosis severity and age (r = 0.311, p = 0.013).&#x0D; CONCLUSION: Serum HIF-1α, VEGF, and TGF-β1 levels were not different among chronic hepatitis B patients based on liver fibrosis severity.

Seroprevalence of Hepatitis B Virus Infection among the Tribal Population of Attapady, Kerala,India

Introduction: Hepatitis B Virus (HBV) infection remains a significant global health concern that may cause acute or chronic hepatitis. Chronically infected patients are at risk for cirrhosis and hepatocellular carcinoma. The disease causes a problem in the tribal communities. There are lack of studies on the prevalence of HBV among the tribal population. Aim: To assess the seroprevalence of HBV infection among the tribal population of Attapady, Kerala. Materials and Methods: This was a community based cross- sectional study conducted on serum samples collected from 269 subjects among the tribal population of Attapady. Serum samples were tested for quantitative antibody to HBsAg (anti-HBs), Hepatitis B surface antigen (HBsAg) and Hepatitis B envelope antigen (HBeAg) Enzyme Linked Immunosorbent Assay (ELISA). Total hepatitis B core antibody (anti-HBc) and IgM antibody to hepatitis B core antigen (anti HBc IgM), frequencies were obtained using proportion and 95% Confidence Interval CI. Results: The seroprevalence of HBsAg was 10.4%. HBeAg was detected in 7.1% of HBsAg positive patients. 21.2% had protective anti-HBs titer. Anti-HBe was detected in five patients. Anti-HBc total and anti-HBc IgM were positive for 26.7% and 2.6%, respectively. Anti-HBc IgM alone and isolated anti-HBc were detected in 1.5% and 5.9 %, respectively. Anti-HBs and anti-HBc total both became positive in 8.6% cases. Conclusion: HBV infection poses a huge burden on tribal health. All HBsAg positive patients should be tested further to determine the stage of the disease. There is need to explore high HBV prevalence areas with studies on associated risk factors to bring out the ongoing transmission process and focus on preventive measures. HBV vaccination, antenatal screening, and health awareness should be given priority to tackle the burden.