RESUMEN
Therapeutics for eradicating hepatitis B virus (HBV) infection are still limited and current nucleos(t)ide analogs (NAs) and interferon are effective in controlling viral replication and improving liver health, but they cannot completely eradicate the hepatitis B virus and only a very small number of patients are cured of it. The TCR-like antibodies recognizing viral peptides presented on human leukocyte antigens (HLA) provide possible tools for targeting and eliminating HBV-infected hepatocytes. Here, we generated three TCR-like antibodies targeting three different HLA-A2.1-presented peptides derived from HBV core and surface proteins. Bispecific antibodies (BsAbs) were developed by fuzing variable fragments of these TCR-like mAbs with an anti-CD3ϵ antibody. Our data demonstrate that the BsAbs could act as T cell engagers, effectively redirecting and activating T cells to target HBV-infected hepatocytes in vitro and in vivo. In HBV-persistent mice expressing human HLA-A2.1, two infusions of BsAbs induced marked and sustained suppression in serum HBsAg levels and also reduced the numbers of HBV-positive hepatocytes. These findings highlighted the therapeutic potential of TCR-like BsAbs as a new strategy to cure hepatitis B.
Asunto(s)
Anticuerpos Biespecíficos , Modelos Animales de Enfermedad , Virus de la Hepatitis B , Hepatitis B , Hepatocitos , Animales , Anticuerpos Biespecíficos/inmunología , Anticuerpos Biespecíficos/farmacología , Hepatocitos/virología , Hepatocitos/inmunología , Ratones , Humanos , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Hepatitis B/inmunología , Hepatitis B/virología , Antígeno HLA-A2/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: This study aimed to determine the prevalence and factors associated with susceptibility to hepatitis B virus (HBV) among cisgender men who have sex with men (MSM) on HIV pre-exposure prophylaxis (PrEP) in Northeastern Brazil. METHODS: This was a cross-sectional, analytical study conducted between September 2021 and June 2023. Participants underwent structured interviews to collect sociodemographic and clinical information, including hepatitis B vaccination history, HIV PrEP use and sexual health history. Blood samples were collected for hepatitis B serologic testing: HBV surface antigen (HBsAg), HBV surface antibody (anti-HBs), total and IgM HBV core antibody (anti-HBc). HBV susceptibility was defined as nonreactive results for all these serological markers. RESULTS: A total of 287 participants were enrolled into the study. The median age of the individuals was 31 years (interquartile range: 27; 36). HBV susceptibility was found in 58 out 286 individuals (20.3%; 95% CI: 15.9-25.2). Seventy-six percent of the participants reported completing the three-dose hepatitis B vaccine schedule. Susceptibility was significantly associated with a monthly income ≤ 5 minimum wages (PR: 2.02; 95% CI: 1.01-4.05), lack of complete hepatitis B vaccination schedule (PR: 4.52; 95% CI: 2.89-7.06), initiation of HIV PrEP (PR: 2.18; 95% CI: 1.21-3.94), duration of six months of HIV PrEP (PR: 2.16; 95% CI: 1.19-3.91), absence of tattoos (PR: 1.55; 95% CI: 1.00-2.40) and no history of sexually transmitted infections (PR: 1.65; 95% CI: 1.07-2.54). CONCLUSION: Our findings highlight the significant burden of HBV susceptibility among MSM on HIV PrEP in Northeastern Brazil. Socioeconomic factors, vaccination status, PrEP use and sexual health behaviors play critical roles in determining susceptibility to HBV. Integrating hepatitis B screening and vaccination into PrEP services is critical for identifying and addressing HBV susceptibility among MSM. Interventions aimed at increasing vaccination coverage and promoting safer sexual practices are essential for mitigating the burden of HBV infection in this population.
Asunto(s)
Infecciones por VIH , Hepatitis B , Homosexualidad Masculina , Profilaxis Pre-Exposición , Humanos , Masculino , Estudios Transversales , Brasil/epidemiología , Adulto , Profilaxis Pre-Exposición/estadística & datos numéricos , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Hepatitis B/prevención & control , Hepatitis B/epidemiología , Homosexualidad Masculina/estadística & datos numéricos , Prevalencia , Virus de la Hepatitis B/inmunología , Susceptibilidad a Enfermedades , Adulto Joven , Factores de Riesgo , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Vacunas contra Hepatitis B/administración & dosificación , Vacunas contra Hepatitis B/inmunologíaRESUMEN
A patient in Japan with HIV began antiretroviral therapy because of acute hepatitis B virus (HBV) 15 years ago, with low hepatitis B surface antibody, and experienced breakthrough HBV reactivation 4 months after switching from bictegravir/emtricitabine/tenofovir alafenamide to cabotegravir/rilpivirine. An immune escape mutation, E164V, was identified in the isolated HBV DNA.
Asunto(s)
Infecciones por VIH , Virus de la Hepatitis B , Hepatitis B , Activación Viral , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Masculino , Hepatitis B/virología , Hepatitis B/tratamiento farmacológico , Piridonas/uso terapéutico , Anticuerpos contra la Hepatitis B/sangre , Anticuerpos contra la Hepatitis B/inmunología , Fármacos Anti-VIH/uso terapéutico , Pirimidinas/uso terapéutico , Persona de Mediana Edad , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , DicetopiperazinasRESUMEN
Introduction: since the introduction of the anti-HBV vaccine into the Expanded Program on Immunization (EPI) in 2005 in Cameroon, vaccination coverage has reached 99.0%. This coverage would indicate an increase in the number of children immune to Hepatitis B Virus (HBV) and a decrease in susceptibility to HBV-infection. This study was conducted to evaluate the effect of the HBV vaccine on pediatric HBV-infection in Yaounde, Cameroon. Methods: this school-based cross-sectional study was conducted from February to May 2016 among 180 children from Nkomo public school. The study population was stratified into two groups: vaccinated (n=95) versus (vs) unvaccinated (n=85). Screening for HBV biomarkers was done using a rapid panel test for detection (HBsAg, HBeAg and anti-HBc) and anti-HBs titer using enzyme linked immunosorbent assay (ELISA). Statistical analyses were done using SPSS v. 22 with p < 0.05 considered significant. Results: the mean age was 9.65 years. HBsAg (p=0.019) and anti-HBc (p=0.001) rates were detected in children aged ≥10 years and children aged < 10 years (95.95% [71/74]) were vaccinated vs 22.64% (24/106) for those aged ≥10 years (OR: 80.86; 95% CI: 23.36%-279.87%, p < 0.0001). According to anti-HBV vaccination status, HBsAg rate varied from [9.41% (8/85) to 1.05% (1/95), p=0.025], HBeAg rate varied from [2.35% (2/85) to 0% (0/95), p= 0.42] and anti-HBc rate ranged from [12.94% (11/85) to 2.10% (2/95), p= 0.011]. Conclusion: despite the variability of the anti-HBs titer, vaccination against HBV has a positive effect on the reduction of HBV-infection in children in tropical settings such as Cameroon.
Asunto(s)
Anticuerpos contra la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Vacunas contra Hepatitis B , Hepatitis B , Programas de Inmunización , Vacunación , Humanos , Camerún/epidemiología , Vacunas contra Hepatitis B/administración & dosificación , Vacunas contra Hepatitis B/inmunología , Estudios Transversales , Hepatitis B/prevención & control , Hepatitis B/epidemiología , Niño , Masculino , Femenino , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Vacunación/estadística & datos numéricos , Adolescente , Cobertura de Vacunación/estadística & datos numéricos , Ensayo de Inmunoadsorción Enzimática , Biomarcadores/sangre , Antígenos e de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/inmunología , Preescolar , Instituciones AcadémicasRESUMEN
Mixed cryoglobulinemia vasculitis (MCV) is caused in ~90% of cases by chronic hepatitis C virus (HCVposMCV) and more rarely by hepatitis B virus (HBV) infection, or apparently noninfectious. HCVposMCV develops in only ~5% of patients with chronic hepatitis C (CHC), but risk factors other than female gender have not been identified so far. We conducted a retrospective case control study investigating whether past active HBV infection, defined by hepatitis B surface antigen (HBsAg) seroclearance and anti-core antibody (HBcAb) positivity, could be a risk factor for developing HCVposMCV. The prevalence of HBsAg seroclearance was 48% within 123 HCVposMCV patients and 29% within 257 CHC patients (p=0.0003). Multiple logistic regression including as variables gender, birth year, age at HBV testing, cirrhosis, and hepatocellular carcinoma, confirmed an association of HBsAg seroclearance with HCVposMCV [adjusted odds ratio (OR) 2.82, 95% confidence interval (95% CI) 1.73-4.59, p<0.0001]. Stratification by gender, however, showed that HBsAg seroclearance was associated with HCVposMCV in male [OR 4.63, 95% CI 2.27-9.48, p<0.0001] and not in female patients [OR 1.85, 95% 95% CI 0.94-3.66, p=0.076]. HBsAg seroclearance, and more likely occult HBV infection, is an independent risk factor for HCVposMCV in male CHC patients.
Asunto(s)
Crioglobulinemia , Antígenos de Superficie de la Hepatitis B , Hepatitis C Crónica , Vasculitis , Humanos , Masculino , Crioglobulinemia/inmunología , Crioglobulinemia/etiología , Crioglobulinemia/sangre , Persona de Mediana Edad , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/inmunología , Estudios Retrospectivos , Factores de Riesgo , Femenino , Anciano , Vasculitis/inmunología , Vasculitis/epidemiología , Vasculitis/etiología , Hepatitis B/complicaciones , Hepatitis B/inmunología , Hepatitis B/epidemiología , Estudios de Casos y Controles , Virus de la Hepatitis B/inmunología , Adulto , Factores Sexuales , Hepacivirus/inmunologíaRESUMEN
The rampant hepatitis B virus (HBV) seriously endangers human health, and hepatitis B surface antigen (HBsAg) is its early diagnostic marker. Therefore, it is crucial to construct a fast and highly sensitive HBsAg detection method. Based on high-efficiency magnetic separation technology and fluorescent composite material labelling technology, an accurate, fast and sensitive fluorescent immunosensing system for HBsAg detection was developed. Immunomagnetic beads constructed from carboxyl-functionalized Fe3O4 nanoparticles (Fe3O4-COOH) with excellent magnetic response performance were used as efficient capture carriers for HBsAg. Immunofluorescence composite microspheres constructed based on ultra-stable polystyrene-coated CsPbBr3 perovskite nanocrystals (CPB@PSAA) with high hydrophilic properties, were excellent fluorescent markers for HBsAg. Using this sensitive sandwich fluorescence sensing system a good linear relationship within the range of 0.2-15 ng/mL was established between HBsAg concentration and fluorescence intensity with a limit of detection (LOD) of 0.05 ng/mL. The system obtained satisfactory results when tested on real human serum samples. The magnetic-assisted fluorescence immune-sandwich sensor system has broad application prospects in biomedicine such as rapid and early diagnosis and effective prevention of infectious diseases.
Asunto(s)
Compuestos de Calcio , Antígenos de Superficie de la Hepatitis B , Interacciones Hidrofóbicas e Hidrofílicas , Límite de Detección , Óxidos , Titanio , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/análisis , Humanos , Óxidos/química , Titanio/química , Compuestos de Calcio/química , Colorantes Fluorescentes/química , Nanopartículas de Magnetita/química , Microesferas , Anticuerpos Inmovilizados/inmunología , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Inmunoensayo/métodosRESUMEN
Fluorescently conjugated antigen-bait systems have been extensively used to identify antigen-specific B cells and probe humoral immunity across different settings. Following this approach, we used HBV antigens to bind the B cell receptor (BCR), permitting antigen-specific B cell detection by flow cytometry. Fluorochromes can either be attached covalently via chemical conjugation to the antigen or attached non-covalently by biotinylating the antigen. Dual-staining antigen-baits (where an antigen is directly conjugated to two distinct fluorochromes) have now been used to identify HBsAg- and HBcAg-specific B cells with a high degree of reliability and specificity. This system can be used to detect and characterize cells ex vivo or adapted to isolate antigen-specific cells using fluorescence-activated cell sorting.
Asunto(s)
Linfocitos B , Citometría de Flujo , Colorantes Fluorescentes , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B Crónica , Humanos , Citometría de Flujo/métodos , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Virus de la Hepatitis B/inmunología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Antígenos de Superficie de la Hepatitis B/inmunología , Colorantes Fluorescentes/química , Coloración y Etiquetado/métodos , Receptores de Antígenos de Linfocitos B/metabolismo , Receptores de Antígenos de Linfocitos B/inmunología , Antígenos del Núcleo de la Hepatitis B/inmunologíaRESUMEN
BACKGROUND: Since Imbach [1] first reported the use of high-dose intravenous immunoglobulin (IVIg) in the treatment of idiopathic thrombocytopenic purpura (ITP) in children, indications for IVIg therapy have been increaseing. At present, IVIg infusion has become an important means of clinical treatment. The phenomenon of anti-HBs and anti-HBc elevation caused by IVIg infusion in patients has been reported in journals, but similar reports in journals related to laboratory diagnosis are rare. METHODS: We reported a case of a patient with immune thrombocytopenia (ITP) which interfered with hepatitis B virus (HBV) serological detection after receiving intravenous IVIg. We used chemiluminescence immunoassay to detect serological markers of HBV. IU/mL was used to represent the detection data of HBsAg and HBsAb and cutoff value was used to represent the detection HBeAg, HBeAb, and HbcAb. RESULTS: The serological markers of HBV were all negative before IVIg infusion. One week after IVIG infusion, the item was tested again, and the results of HBsAb, HBeAb, and HBcAb were positive. As the time increased after infusion, HBsAb, HBeAb, and HBcAb in the patient gradually decreased. CONCLUSIONS: After IVIg infusion, the sudden positive change of HBsAb, HBeAb, and HbcAb in the patient's body was not caused by HBV infection, but caused by the infusion of foreign antibody. This case study shows that physicians should be particularly careful when interpreting results in patients treated with intravenous IVIg involving viral hepatitis B.
Asunto(s)
Anticuerpos contra la Hepatitis B , Virus de la Hepatitis B , Hepatitis B , Inmunoglobulinas Intravenosas , Púrpura Trombocitopénica Idiopática , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunoglobulinas Intravenosas/administración & dosificación , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/inmunología , Hepatitis B/diagnóstico , Hepatitis B/inmunología , Hepatitis B/sangre , Anticuerpos contra la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Pruebas Serológicas/métodos , Masculino , FemeninoRESUMEN
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 (â¼30 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.
Asunto(s)
Técnicas Biosensibles , Antígenos de Superficie de la Hepatitis B , Hepatitis B , Redes Neurales de la Computación , Antígenos de Superficie de la Hepatitis B/análisis , Antígenos de Superficie de la Hepatitis B/inmunología , Humanos , Hepatitis B/diagnóstico , Hepatitis B/virología , Hepatitis B/inmunología , Hepatitis B/sangre , Técnicas Biosensibles/métodos , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Límite de Detección , Oro/química , Aprendizaje Profundo , Resonancia por Plasmón de Superficie/métodos , Sistemas de Atención de PuntoRESUMEN
The question of whether patients in the immune-tolerant (IT) phase of chronic hepatitis B virus (HBV) infection should undergo antiviral therapy and determine the optimal regimen remains unclear. A comprehensive search of PubMed, Embase, MEDLINE, Cochrane Library, and Wanfang Data from inception to 5 December 2023, was conducted. Studies reporting on key outcomes such as HBV DNA undetectability, HBeAg loss or seroconversion, HBsAg loss or seroconversion, and hepatocellular carcinoma (HCC) incidence in patients in the IT phase of chronic HBV infection were included. In total, 23 studies were incorporated. Approximately 4% of patients in the IT phase achieved spontaneous HBeAg loss over 48 weeks of follow-up. Antiviral therapy demonstrated a favourable impact on HBV DNA negative conversion (Children: risk ratios [RR] = 6.83, 95% CI: 2.90-16.05; Adults: RR = 25.84, 95% CI: 6.47-103.31) and HBsAg loss rates (Children: RR = 9.49, 95% CI: 1.74-51.76; Adults: RR = 7.35, 95% CI: 1.41-38.27) for patients in the IT phase. Subgroup analysis revealed that in adult patients in the IT phase, interferon plus nucleos(t)ide analogues (NA)-treated patients exhibited a higher pooled rate of HBsAg loss or seroconversion than those treated with NA monotherapy (9% vs. 0%). Additionally, the pooled annual HCC incidence for patients in the IT phase was 3.03 cases per 1000 person-years (95% CI: 0.99-5.88). Adult patients in the IT phase had a significantly lower HCC incidence risk than HBeAg-positive indeterminate phase patients (RR = 0.46, 95% CI: 0.32-0.66), with no significant differences observed between IT and immune-active phases. Presently, there is insufficient evidence solely based on reducing the risk of HCC incidence, to recommend treating patients in the IT phase of chronic HBV infection. However, both adult and paediatric patients in the IT phase responded well to antiviral therapy, showing favourable rates of HBsAg loss or seroconversion.
Asunto(s)
Antivirales , Carcinoma Hepatocelular , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/inmunología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/inmunología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/inmunología , Antivirales/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Incidencia , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , ADN Viral/sangre , Tolerancia Inmunológica , Resultado del Tratamiento , SeroconversiónRESUMEN
A highly sensitive and reliable Hepatitis B virus surface antigen (HBsAg) measurement is essential to universal screening, timely diagnosis, and management of Hepatitis B virus (HBV) infection. This study aimed to evaluate the performance of MAGLUMI HBsAg chemiluminescence immunoassay (CLIA). MAGLUMI HBsAg (CLIA) was compared against ARCHITECT HBsAg. 411 HBsAg positive samples, including different stages of infection, genotypes, subtypes, mutants, and 30 seroconversion panels were tested to evaluate diagnostic sensitivity. Diagnostic specificity was evaluated by testing 205 hospitalized samples and 5101 blood donor samples. Precision, limit of blank (LoB), limit of detection (LoD), and linearity were also verified. The diagnostic sensitivity of the MAGLUMI HBsAg (CLIA) was 100% with better seroconversion sensitivity than ARCHITECT HBsAg. The MAGLUMI HBsAg (CLIA) has optimal detection efficacy for HBV subgenotypes samples. The analytical sensitivity is 0.039 IU/mL. The initial diagnostic specificity is 99.63% on blood donors and 96.59% on hospitalized samples. The verification data demonstrated high repeatability, a LoB of 0.02 IU/mL, LoD of 0.05 IU/mL and an excellent linearity of 0.050-250 IU/mL (R2 = 0.9946). The MAGLUMI HBsAg (CLIA) is proved a highly sensitive and reliable assay with optimal subgenotype detection efficacy.
Asunto(s)
Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B , Mediciones Luminiscentes , Sensibilidad y Especificidad , Humanos , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Hepatitis B/diagnóstico , Hepatitis B/sangre , Mediciones Luminiscentes/métodos , Inmunoensayo/métodos , Inmunoensayo/normas , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Genotipo , Adulto , Femenino , Masculino , Persona de Mediana Edad , Adulto Joven , Reproducibilidad de los Resultados , Anciano , AdolescenteRESUMEN
The development of high-purity antigens promotes the urgent need of novel adjuvant with the capability to trigger high levels of immune response. Polyinosinic-polycytidylic (Poly(I:C)) is a synthetic double-stranded RNA (dsRNA) that can engage Toll-like receptor 3 (TLR3) to initiate immune responses. However, the Poly(I:C)-induced toxicity and inefficient delivery prevent its applications. In our study, combination adjuvants are formulated by aluminum oxyhydroxide nanorods (AlOOH NRs) and Poly(I:C), named Al-Poly(I:C), and the covalent interaction between the two components is further demonstrated. Al-Poly(I:C) mediates enhanced humoral and cellular immune responses in three antigen models, i.e., HBsAg virus-like particles (VLPs), human papilloma virus (HPV) VLPs and varicella-zoster virus (VZV) glycoprotein E (gE). Further mechanistic studies demonstrate that the dose and molecular weight (MW) of Poly(I:C) determine the physicochemical properties and adjuvanticity of the Al-Poly(I:C) combination adjuvants. Al-Poly(I:C) with higher Poly(I:C) dose promotes antigen-bearing dendritic cells (DCs) recruitment and B cells proliferation in lymph nodes. Al-Poly(I:C) formulated with higher MW Poly(I:C) induces higher activation of helper T cells, B cells, and CTLs. This study demonstrates that Al-Poly(I:C) potentiates the humoral and cellular responses in vaccine formulations. It offers insights for adjuvant design to meet the formulation requirements in both prophylactic and therapeutic vaccines.
Asunto(s)
Adyuvantes Inmunológicos , Poli I-C , Poli I-C/administración & dosificación , Poli I-C/farmacología , Animales , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/química , Femenino , Ratones Endogámicos C57BL , Hidróxido de Aluminio/administración & dosificación , Hidróxido de Aluminio/química , Nanotubos/química , Inmunidad Humoral/efectos de los fármacos , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/administración & dosificación , Humanos , Ratones , Inmunidad Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Vacunas/administración & dosificación , Vacunas/inmunología , Óxido de AluminioRESUMEN
BACKGROUND: Occult hepatitis B infection (OBI) refers to the presence of hepatitis B virus (HBV) DNA in the serum or liver of individuals who tested negative for HBV surface antigen (HBsAg). This study aimed to determine seropositivity for antibodies against HBV core antigen (anti-HBc) and the frequency of OBI among the HBsAg non-reactive blood donors in Mashhad, northeastern Iran. METHODS: In this cross-sectional study, serum samples of HBsAg-negative blood donors were examined for anti-HBc during June and August 2018. Anti-HBc-positive samples were tested for antibodies against HBsAg (anti-HBs), and those with negative results were classified as isolated anti-HBc cases. The presence of HBV DNA in the C, S, and X gene regions was assessed by a qualitative real-time polymerase chain reaction method in all HBsAg-negative samples. OBI subjects were detected by the presence of at least one HBV genomic region. RESULTS: Of 540 HBsAg-negative donors, 29 (5.4%; 95% confidence interval: 3.6-7.6%) showed seroreactivity for anti-HBc, of whom 18 individuals were also seropositive for anti-HBs. All donors showed negative results for all three HBV genes regardless of their serum anti-HBc status. CONCLUSION: Based on our findings, we suggest routine screening of Iranian blood donation volunteers for serum anti-HBc and anti-HBs but not HBV DNA.
Asunto(s)
Donantes de Sangre , ADN Viral , Anticuerpos contra la Hepatitis B , Antígenos del Núcleo de la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B , Humanos , Estudios Transversales , Irán/epidemiología , Donantes de Sangre/estadística & datos numéricos , ADN Viral/sangre , Adulto , Masculino , Anticuerpos contra la Hepatitis B/sangre , Hepatitis B/epidemiología , Hepatitis B/sangre , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos del Núcleo de la Hepatitis B/sangre , Persona de Mediana Edad , Adulto Joven , Prevalencia , AdolescenteRESUMEN
Cytokines may related to intrauterine Hepatitis B virus (HBV) transmission. 205 HBsAg(+) pregnant cases and 74 HBsAg(-) women were included. Neonatal blood samples were taken within 24 h of delivery and before HBV vaccinations. Serological HBV biomarkers and cytokines were detected. 21.9 % of the newborns from HBsAg(+) women were intrauterinally transmitted, including 7.3 % with dominant transmission (DBT) and 14.6 % occult transmission (OBT). HBV DNA load (odd ratio [OR], 1.44; 95 % confidence interval [CI], 1.05-1.98), interferon-γ (IFN-γ) (OR, 1.01; 95 %CI, 1.00-1.02) and toll-like receptor 9 (TLR9) (OR, 1.27; 95 %CI, 1.06-1.52) positively correlated with DBT. Only IFN-γ (OR, 1.01; 95 %CI, 1.00-1.01) positively associated with OBT. According to the generated restricted cubic spline, TLR9 was positively correlates with rise of DBT in a log-shape. It may be possible to develop a nomogram which intercalates these factors to predict intrauterine HBV transmissions. Further research should consider immune processes involved in chorioamnionitis.
Asunto(s)
Citocinas , Virus de la Hepatitis B , Hepatitis B , Transmisión Vertical de Enfermedad Infecciosa , Receptor Toll-Like 9 , Humanos , Femenino , Embarazo , Estudios Transversales , Hepatitis B/transmisión , Hepatitis B/sangre , Hepatitis B/inmunología , China/epidemiología , Adulto , Citocinas/sangre , Virus de la Hepatitis B/inmunología , Recién Nacido , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , ADN Viral/sangre , Interferón gamma/sangre , Complicaciones Infecciosas del Embarazo/sangre , Complicaciones Infecciosas del Embarazo/virologíaRESUMEN
Aluminum salts still remain as the most popular adjuvants in marketed human prophylactic vaccines due to their capability to trigger humoral immune responses with a good safety record. However, insufficient induction of cellular immune responses limits their further applications. In this study, we prepare a library of silicon (Si)- or calcium (Ca)-doped aluminum oxyhydroxide (AlOOH) nanoadjuvants. They exhibit well-controlled physicochemical properties, and the dopants are homogeneously distributed in nanoadjuvants. By using Hepatitis B surface antigen (HBsAg) as the model antigen, doped AlOOH nanoadjuvants mediate higher antigen uptake and promote lysosome escape of HBsAg through lysosomal rupture induced by the dissolution of the dopant in the lysosomes in bone marrow-derived dendritic cells (BMDCs). Additionally, doped nanoadjuvants trigger higher antigen accumulation and immune cell activation in draining lymph nodes. In HBsAg and varicella-zoster virus glycoprotein E (gE) vaccination models, doped nanoadjuvants induce high IgG titer, activations of CD4+ and CD8+ T cells, cytotoxic T lymphocytes, and generations of effector memory T cells. Doping of aluminum salt-based adjuvants with biological safety profiles and immunostimulating capability is a potential strategy to mediate robust humoral and cellular immunity. It potentiates the applications of engineered adjuvants in the development of vaccines with coordinated immune responses.
Asunto(s)
Adyuvantes Inmunológicos , Hidróxido de Aluminio , Calcio , Antígenos de Superficie de la Hepatitis B , Silicio , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/farmacología , Animales , Silicio/química , Ratones , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/química , Calcio/química , Hidróxido de Aluminio/química , Hidróxido de Aluminio/farmacología , Ratones Endogámicos C57BL , Femenino , Vacunas/inmunología , Vacunas/química , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Nanopartículas/química , Humanos , Óxido de AluminioRESUMEN
Interferon-alpha (IFN-α) is a first-line drug for treating chronic hepatitis B (CHB). Guanylate-binding protein 1 (GBP1) is one of the interferon-stimulating factors, which participates in the innate immunity of the host and plays an antiviral and antibacterial role. In this study, we explored how GBP1 is involved in IFN-α antiviral activity against HBV. Before being gathered, HepG2-NTCP and HepG2 2.15 cells were transfected with the wild-type hGBP1 plasmid or si-GBP1, respectively, and followed by stimulation with Peg-IFNα-2b. We systematically explored the role of GBP1 in regulating HBV infection in cell models. Additionally, we also examined GBP1 levels in CHB patients. GBP1 activity increased, and its half-life was prolonged after HBV infection. Overexpression of GBP1 inhibited the production of HBsAg and HBeAg, as well as HBs protein and HBV total RNA levels, whereas silencing of GBP1 inhibited its ability to block viral infections. Interestingly, overexpressing GBP1 co-treatment with Peg-IFNα-2b further increased the antiviral effect of IFN-α, while GBP1 silencing co-treatment with Peg-IFNα-2b partly restored its inhibitory effect on HBV. Mechanistically, GBP1 mediates the anti-HBV response of Peg-IFNα-2b by targeting HBs. Analysis of clinical samples revealed that GBP1 was elevated in CHB patients and increased with Peg-IFNα-2b treatment, while GBP1 showed good stability in the interferon response group. Our study demonstrates that GBP1 inhibits HBV replication and promotes HBsAg clearance. It is possible to achieve antiviral effects through the regulation of IFN-α induced immune responses in response to HBV.
Asunto(s)
Antivirales , Proteínas de Unión al GTP , Virus de la Hepatitis B , Hepatitis B Crónica , Interferón-alfa , Humanos , Interferón-alfa/farmacología , Interferón-alfa/inmunología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/fisiología , Antivirales/farmacología , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/inmunología , Células Hep G2 , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Hepatitis B Crónica/inmunología , Masculino , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/metabolismo , Femenino , Adulto , Replicación Viral/efectos de los fármacos , Hepatitis B/virología , Hepatitis B/inmunología , Hepatitis B/tratamiento farmacológicoAsunto(s)
Anticuerpos contra la Hepatitis B , Hepatitis B , Homosexualidad Masculina , Salud Sexual , Humanos , Masculino , Homosexualidad Masculina/estadística & datos numéricos , Reino Unido/epidemiología , Anticuerpos contra la Hepatitis B/sangre , Hepatitis B/epidemiología , Hepatitis B/inmunología , Adulto , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Adulto Joven , Conducta SexualRESUMEN
The concurrent seropositivity of HBsAg and anti-HBs has been described among patients with chronic hepatitis B (CHB), but its prevalence is variable. HBV S-gene mutations can affect the antigenicity of HBsAg. Patients with mutations in the 'α' determinant region of the S gene can develop severe HBV reactivation under immunosuppression. In this study at a tertiary liver center in the United States, we evaluated the frequency and virological characteristics of the HBsAg mutations among CHB patients with the presence of both HBsAg and anti-HBs. In this cohort, 45 (2.1%) of 2178 patients were identified to have a coexistence of HBsAg and anti-HBs, and 24 had available sera for the genome analysis of the Pre-S1, Pre-S2, and S regions. The frequency of mutations in the S gene was significantly higher among those older than 50 years (mean 8.5 vs. 5.4 mutations per subject, p = 0.03). Twelve patients (50%) had mutations in the 'α' determinant region of the S gene. Mutations at amino acid position 126 were most common in eight subjects. Three had a mutation at position 133. Only one patient had a mutation at position 145-the classic vaccine-escape mutation. Despite the universal HBV vaccination program, the vaccine-escape mutant is rare in our cohort of predominantly Asian patients.
Asunto(s)
Anticuerpos contra la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B Crónica , Mutación , Centros de Atención Terciaria , Humanos , Antígenos de Superficie de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/inmunología , Femenino , Masculino , Persona de Mediana Edad , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Adulto , Anticuerpos contra la Hepatitis B/sangre , Anticuerpos contra la Hepatitis B/inmunología , Hepatitis B Crónica/virología , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/epidemiología , Estados Unidos/epidemiología , Evasión Inmune/genética , Anciano , Prevalencia , Adulto JovenRESUMEN
Hepatitis B virus reactivation (HBV-R) is a serious complication that can occur in patients with resolved HBV infection during cancer chemotherapy. We examined the levels of HBV surface antibody (HBsAb) and HBV core antibody (HBcAb) to assess the incidence of HBV-R in cancer patients including hematopoietic stem cell transplantation (HSCT) and rituximab administration. This retrospective cohort study included 590 patients with resolved HBV infection. The incidence of HBV-R was evaluated 761.5 (range, 90-3898) days after the inititiation of chemotherapy. Of the patients, 13 (2.2%) developed HBV-R after the start of chemotherapy. All 13 patients exhibited lower HBsAb (<100 mIU/mL) levels at baseline. A higher level of HBcAb (≥100 cut off index (C.O.I.)) was a possible risk factor for HBV-R as well as HSCT and rituximab administration. The simultaneous presence of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I. increased the risk of HBV-R by 18.5%. Patients treated with rituximab were at a higher risk of HBV-R (18.4%) despite having HBcAb <100 C.O.I. Our results suggest that assessment of HBsAb and HBcAb levels prior to the chemotherapy is important for identifying patients at high risk of HBV-R, especially in solid cancers without HSCT and rituximab administration.
Asunto(s)
Anticuerpos contra la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B , Rituximab , Activación Viral , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anticuerpos contra la Hepatitis B/sangre , Anticuerpos contra la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/fisiología , Activación Viral/efectos de los fármacos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Adulto , Anciano , Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Adulto Joven , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos del Núcleo de la Hepatitis B/sangre , Anciano de 80 o más Años , AdolescenteRESUMEN
Although a sizable number of pregnant women patronize Traditional Birth Attendants (TBAs) for deliveries in Nigeria, efforts to prevent or reduce the risk of HBV transmission are not targeted at the TBAs and the pregnant women patronizing them. This may be linked to the dearth of information on the serological profiles of HBV among this cohort. We, therefore, show the serological profiles of HBV among the cohort. One hundred and seventy pregnant women and 91 TBAs participated in this study between May and July 2019. Serological markers of HBV infection were assayed using ELISA. A prevalence of, 8.0% (95% CI: 5.0% - 11.5%) for HBsAg, 0.8% (95% CI: 0.0% - 1.9%) for HBeAg, 2.7% (95% CI: 0.8% - 5.0%) for HBcIgM, 26.1% (95% CI: 20.7% - 31.4%) for anti-HBs, 21.5% (95% CI: 16.5% - 25.4%) for anti-HBe and 67.0% (95% CI: 60.9% - 72.8%) for anti-HBc was found indicating a high percentage of carriers. Although 32 (12.3%) of the entire participants claimed to be fully vaccinated, serological evidence was only detected in 4 (12.5%). The high percentage of carriers and low evidence of vaccination necessitate intensified efforts to ensure that adequate interventions are made available and accessible to the TBAs and the pregnant women patronizing them (including newborn babies).