BNT162b2-boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19.

Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) has been reported to be superior in inducing protective immunity compared to repeated application of the same vaccine.

Differential Relapse Patterns After Discontinuation of Entecavir vs Tenofovir Disoproxil Fumarate in Chronic Hepatitis B.

Background And Aims: Whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differentially affect relapse and outcomes following treatment discontinuation across different patient subpopulations remains unclear. We aimed to compare rates of off-therapy hepatitis B surface antigen (HBsAg) loss, virological and clinical relapse, and retreatment between chronic hepatitis B (CHB) patients who discontinued TDF or ETV therapy.

Methods: This study included 1402 virally suppressed CHB patients who stopped either ETV (n = 981) or TDF (n = 421) therapy between 2001 and 2020 from 13 participating centers across North America, Europe, and Asia.

Improving personalized tumor growth predictions using a Bayesian combination of mechanistic modeling and machine learning.

Background: In clinical practice, a plethora of medical examinations are conducted to assess the state of a patient's pathology producing a variety of clinical data. However, investigation of these data faces two major challenges. Firstly, we lack the knowledge of the mechanisms involved in regulating these data variables, and secondly, data collection is sparse in time since it relies on patient's clinical presentation.

Rapid SARS-CoV-2 Adaptation to Available Cellular Proteases.

Recent emergence of SARS-CoV-1 variants demonstrates the potential of this virus for targeted evolution, despite its overall genomic stability. Here we show the dynamics and the mechanisms behind the rapid adaptation of SARS-CoV-2 to growth in Vero E6 cells. The selective advantage for growth in Vero E6 cells is due to increased cleavage efficiency by cathepsins at the mutated S1/S2 site.

Single-cell transcriptional profiling of splenic fibroblasts reveals subset-specific innate immune signatures in homeostasis and during viral infection.

Our understanding of the composition and functions of splenic stromal cells remains incomplete. Here, based on analysis of over 20,000 single cell transcriptomes of splenic fibroblasts, we characterized the phenotypic and functional heterogeneity of these cells in healthy state and during virus infection. We describe eleven transcriptionally distinct fibroblastic cell clusters, reassuring known subsets and revealing yet unascertained heterogeneity amongst fibroblasts occupying diverse splenic niches.

Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study).

Background & Aims: Functional cure, defined based on hepatitis B surface antigen (HBsAg) loss, is rare during nucleos(t)ide analogue (NA) therapy and guidelines on finite NA therapy have not been well established. We aim to analyze off-therapy outcomes after NA cessation in a large, international, multicenter, multiethnic cohort of patients with chronic hepatitis B (CHB).

Methods: This cohort study included patients with virally suppressed CHB who were hepatitis B e antigen (HBeAg)-negative and stopped NA therapy.

Humoral immune response following prime and boost BNT162b2 vaccination in people living with HIV on antiretroviral therapy.

Objectives: People living with HIV (PLWH) with low CD4 T-cell counts may be at a higher risk for severe coronavirus disease 2019 (COVID-19) outcomes and in need of efficient vaccination. The World Health Organization (WHO) now recommends prioritizing PLHIV for COVID-19 vaccination. Data on immune responses after messenger RNA (mRNA) vaccination in PLHIV in relation to CD4 counts are scarce.

Impact of HBsAg and HBcrAg levels on phenotype and function of HBV-specific T cells in patients with chronic hepatitis B virus infection.

Objective: Hepatitis B virus (HBV)-specific T cells are main effector cells in the control of HBV infection and hepatitis B surface antigen (HBsAg) is suggested to be a critical factor in the impaired immune response, a hallmark of chronic HBV infection. In addition to HBsAg, other viral markers such as hepatitis B core-related antigen (HBcrAg) are available, but their potential association with HBV-specific immune responses is not defined yet, which will be important if these markers are used for patient stratification for novel therapies aimed at functional HBV cure.

Design: We analysed T cell responses in 92 patients with hepatitis B e antigen negative chronic HBV infection with different HBsAg and HBcrAg levels.

A versatile genetic toolbox for Prevotella copri enables studying polysaccharide utilization systems.

Prevotella copri is a prevalent inhabitant of the human gut and has been associated with plant-rich diet consumption and diverse health states. The underlying genetic basis of these associations remains enigmatic due to the lack of genetic tools. Here, we developed a novel versatile genetic toolbox for rapid and efficient genetic insertion and allelic exchange applicable to P.

Epigenome-Wide DNA Methylation and Pesticide Use in the Agricultural Lung Health Study.

Background: Pesticide exposure is associated with many long-term health outcomes; the potential underlying mechanisms are not well established for most associations. Epigenetic modifications, such as DNA methylation, may contribute. Individual pesticides may be associated with specific DNA methylation patterns but no epigenome-wide association study (EWAS) has evaluated methylation in relation to individual pesticides.

Case Report: Convalescent Plasma Therapy Induced Anti-SARS-CoV-2 T Cell Expansion, NK Cell Maturation and Virus Clearance in a B Cell Deficient Patient After CD19 CAR T Cell Therapy.

Here, we described the case of a B cell-deficient patient after CD19 CAR-T cell therapy for refractory B cell Non-Hodgkin Lymphoma with protracted coronavirus disease 2019 (COVID-19). For weeks, this patient only inefficiently contained the virus while convalescent plasma transfusion correlated with virus clearance. Interestingly, following convalescent plasma therapy natural killer cells matured and virus-specific T cells expanded, presumably allowing virus clearance and recovery from the disease.

Cellular and humoral immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on haemodialysis.

Background: Patients with chronic renal insufficiency on maintenance haemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only a few studies have addressed SARS-CoV-2 vaccine elicited immunity in this immunocompromised population.

Methods: We assessed immunogenicity of the mRNA vaccine BNT162b2 in at-risk dialysis patients and characterised systemic cellular and humoral immune responses in serum and saliva using interferon γ release assay and multiplex-based cytokine and immunoglobulin measurements.

Antiviral Activity of Influenza A Virus Defective Interfering Particles against SARS-CoV-2 Replication In Vitro through Stimulation of Innate Immunity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) emerged in late 2019 and resulted in a devastating pandemic. Although the first approved vaccines were already administered by the end of 2020, worldwide vaccine availability is still limited. Moreover, immune escape variants of the virus are emerging against which the current vaccines may confer only limited protection.

Identification of cell lines CL-14, CL-40 and CAL-51 as suitable models for SARS-CoV-2 infection studies.

The SARS-CoV-2 pandemic is a major global threat that sparked global research efforts. Pre-clinical and biochemical SARS-CoV-2 studies firstly rely on cell culture experiments where the importance of choosing an appropriate cell culture model is often underestimated. We here present a bottom-up approach to identify suitable permissive cancer cell lines for drug screening and virus research.

Humoral and Cellular Immune Responses Against Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Human Coronaviruses After Single BNT162b2 Vaccination.

Background: Vaccine-induced neutralizing antibodies are key in combating the coronavirus disease 2019 (COVID-19) pandemic. However, delays of boost immunization due to limited availability of vaccines may leave individuals vulnerable to infection and prolonged or severe disease courses. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC)-B.

Distinct Immune Imprints of Post-Liver Transplantation Hepatitis C Persist Despite Viral Clearance.

Recurrence or de novo infection of hepatitis C virus (HCV) after liver transplantation (LT) has been associated with progressive graft hepatitis that can be improved by treatment with novel direct-acting antivirals. Cases of rejection episodes have been described during and after HCV treatment. The evolution of innate and adaptive immune response during and after cure of HCV LT is unknown.

Exploring beyond clinical routine SARS-CoV-2 serology using MultiCoV-Ab to evaluate endemic coronavirus cross-reactivity.

The humoral immune response to SARS-CoV-2 is a benchmark for immunity and detailed analysis is required to understand the manifestation and progression of COVID-19, monitor seroconversion within the general population, and support vaccine development. The majority of currently available commercial serological assays only quantify the SARS-CoV-2 antibody response against individual antigens, limiting our understanding of the immune response. To overcome this, we have developed a multiplex immunoassay (MultiCoV-Ab) including spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses.

Rate of Immune Complex Cycling in Follicular Dendritic Cells Determines the Extent of Protecting Antigen Integrity and Availability to Germinal Center B Cells.

Follicular dendritic cells (FDCs) retain immune complexes (ICs) for prolonged time periods and are important for germinal center (GC) reactions. ICs undergo periodic cycling in FDCs, a mechanism supporting an extended half-life of Ag. Based on experimental data, we estimated that the average residence time of PE-ICs on FDC surface and interior were 21 and 36 min, respectively.

Modulation of inflammatory responses by gastrointestinal Prevotella spp. - From associations to functional studies.

Numerous studies have associated alterations in the gut microbiota composition with almost every known inflammatory disease. However, proving the biological relevance of distinct microbial signatures and linking specific microorganisms to host phenotypes, remains a considerable challenge. Correspondingly, increased abundance of members of Prevotella genus within microbial communities colonizing distinct mucosal surfaces has been found in individuals diagnosed with rheumatoid arthritis, periodontitis, metabolic disorders, and intestinal and vaginal dysbiosis.

Generation of two human ISG15 knockout iPSC clones using CRISPR/Cas9 editing.

Interferon stimulated gene 15 (ISG15) is one of the most highly upregulated proteins in response to viral infection and is involved in numerous pathways with multiple mechanisms of actions. ISG15 deficiency has been reported to induce type I interferonopathy owing to defective negative regulation of IFN-I signalling as well as enhanced antiviral protection. Here, we have generated ISG15 knockout clones from human iPSCs, which provide useful cell resources to study mechanisms of ISG15 deficiency and gain more insight into the biological function of ISG15.

Shared DNA methylation signatures in childhood allergy: The MeDALL study.

Background: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema.

Objective: We sought to identify DNA methylation profiles associated with childhood allergy.

Methods: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design.