Respiratory syncytial virus infection in patients with haematological diseases: a retrospective multicentre study.

Purpose: This study aims to evaluate the burden of respiratory syncytial virus (RSV) infections in patients with haematological diseases. It seeks to analyse the relevance of prevention, diagnosis and treatment of RSV infections.

Methods: A multi-centre, retrospective study was conducted across University Hospitals in Cologne, Düsseldorf, Bonn, and the University Medical Centre Hamburg-Eppendorf between Jan 2016 and Aug 2023.

Tertiary lymphoid structures in pancreatic cancer are structurally homologous, share gene expression patterns and B-cell clones with secondary lymphoid organs but show increased T-cell activation.

Tertiary lymphoid structures (TLS) in cancer are considered ectopic hotspots for immune activation that are similar to lymphoid follicles in secondary lymphoid organs (SLO). This study elucidates shared and TLS/SLO-specific features in pancreatic ductal adenocarcinoma (PDAC). TLS abundance was related to superior survival and T-cell abundance in 110 treatment-naïve PDAC samples, underlining their clinical relevance.

Semi-mechanistic population pharmacokinetic modeling of DZIF-10c, a neutralizing antibody against SARS-Cov-2: predicting systemic and lung exposure following inhaled and intravenous administration.

DZIF-10c (BI 767551) is a recombinant human monoclonal antibody of the IgG1 kappa isotype. It acts as a SARS-CoV-2 neutralizing antibody. DZIF-10c has been developed for both systemic exposure by intravenous infusion as well as for specific exposure to the respiratory tract by application as an inhaled aerosol generated by a nebulizer.

Protocol for developing Pseudomonas aeruginosa type III secretion system-neutralizing monoclonal antibodies from human B cells.

Monoclonal antibodies (mAbs) targeting bacterial virulence factors may represent promising therapeutics in the fight against severe bacterial infections. Here, we present an approach for developing human-derived antibodies targeting the type III secretion system (T3SS) of Pseudomonas aeruginosa (PA) by neutralizing the function of the T3SS-tip protein PcrV. The protocol involves identifying individuals with protective antibodies, isolating PcrV-specific B cells from these individuals, and producing and testing anti-PcrV mAbs derived from single B cells.

A human monoclonal antibody neutralizing SARS-CoV-2 Omicron variants containing the L452R mutation.

The effectiveness of SARS-CoV-2 therapeutic antibodies targeting the spike (S) receptor-binding domain (RBD) has been hampered by the emergence of variants of concern (VOCs), which have acquired mutations to escape neutralizing antibodies (nAbs). These mutations are not evenly distributed on the RBD surface but cluster on several distinct surfaces, suggesting an influence of the targeted epitope on the capacity to neutralize a broad range of VOCs. Here, we identified a potent nAb from convalescent patients targeting the receptor-binding domain of a broad range of SARS-CoV-2 VOCs.

Blocking the angiopoietin-2-dependent integrin β-1 signaling axis abrogates small cell lung cancer invasion and metastasis.

Small cell lung cancer (SCLC) is the most aggressive lung cancer entity with an extremely limited therapeutic outcome. Most patients are diagnosed at an extensive stage. However, the molecular mechanisms driving SCLC invasion and metastasis remain largely elusive.

CARs derived from broadly neutralizing, human monoclonal antibodies identified by single B cell sorting target hepatitis B virus-positive cells.

To design new CARs targeting hepatitis B virus (HBV), we isolated human monoclonal antibodies recognizing the HBV envelope proteins from single B cells of a patient with a resolved infection. HBV-specific memory B cells were isolated by incubating peripheral blood mononuclear cells with biotinylated hepatitis B surface antigen (HBsAg), followed by single-cell flow cytometry-based sorting of live, CD19 IgG HBsAg cells. Amplification and sequencing of immunoglobulin genes from single memory B cells identified variable heavy and light chain sequences.

SARS-CoV-2 Test-to-Stay in Daycare.

Background And Objectives: Test-to-stay concepts apply serial testing of children in daycare after exposure to SARS-CoV-2 without use of quarantine. This study aims to assess the safety of a test-to-stay screening in daycare facilities.

Methods: 714 daycare facilities and approximately 50 000 children ≤6 years in Cologne, Germany participated in a SARS-CoV-2 Pool-polymerase chain reaction (PCR) screening from March 2021 to April 2022.

Semen enhances transmitted/founder HIV-1 infection and only marginally reduces antiviral activity of broadly neutralizing antibodies.

Topically applied microbicides may play a critical role in preventing sexual transmission of human immunodeficiency virus type 1 (HIV-1); however, their efficacy can be compromised by amyloid fibrils present in semen, which significantly increase HIV-1 infectivity. This phenomenon may have contributed to the failure of most microbicide candidates in clinical settings. Understanding the impact of semen on microbicide effectiveness is thus crucial.

Hybrid immunity to SARS-CoV-2 in patients with chronic lymphocytic leukemia.

Objective: Preventing severe COVID-19 remains a priority globally, particularly in the immunocompromised population. As shown in healthy individuals, immunity against SARS-CoV-2 can be yielded by previous infection, vaccination, or both (hybrid immunity). The objective of this observation study was to investigate hybrid immunity in patients with chronic lymphocytic leukemia (CLL).

Torque Teno Virus Load Is Associated With Centers for Disease Control and Prevention Stage and CD4+ Cell Count in People Living With Human Immunodeficiency Virus but Seems Unrelated to AIDS-Defining Events and Human Pegivirus Load.

Background: Torque teno virus (TTV) is part of the human virome. TTV load was related to the immune status in patients after organ transplantation. We hypothesize that TTV load could be an additional marker for immune function in people living with HIV (PLWH).

Five-year single-center analysis of cytomegalovirus viremia in kidney transplant recipients and possible implication for novel prophylactic therapy approaches.

Background: Cytomegalovirus (CMV) infections are a common complication after kidney transplantation (KTx) and negatively affecting patient outcome. Valganciclovir (VGC) prophylaxis is often limited by drug-induced side effects and dose reduction due to decline in kidney function.

Method: In the present study, episodes of CMV viremia in the first year after KTx in a cohort of 316 recipients were analyzed retrospectively to identify risk factors linked to persistent infections.

LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells.

Introduction: Epstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for transformation remains to be identified.

Methods: Here, we addressed this question by transducing human peripheral B cells from EBV-negative donors with retrovirus expressing the latent EBV genes encoding Latent Membrane Protein (LMP) 1 and 2A and Epstein-Barr Nuclear Antigen (EBNA) 2.

Somatic hypermutation introduces bystander mutations that prepare SARS-CoV-2 antibodies for emerging variants.

Somatic hypermutation (SHM) drives affinity maturation and continues over months in SARS-CoV-2-neutralizing antibodies (nAbs). However, several potent SARS-CoV-2 antibodies carry no or only a few mutations, leaving the question of how ongoing SHM affects neutralization unclear. Here, we reverted variable region mutations of 92 antibodies and tested their impact on SARS-CoV-2 binding and neutralization.

Bridging the gap - estimation of 2022/2023 SARS-CoV-2 healthcare burden in Germany based on multidimensional data from a rapid epidemic panel.

Objectives: Throughout the SARS-CoV-2 pandemic, Germany like other countries lacked adaptive population-based panels to monitor the spread of epidemic diseases.

Methods: To fill a gap in population-based estimates needed for winter 2022/23 we resampled in the German SARS-CoV-2 cohort study MuSPAD in mid-2022, including characterization of systemic cellular and humoral immune responses by interferon-γ-release assay (IGRA) and CLIA/IVN assay. We were able to confirm categorization of our study population into four groups with differing protection levels against severe COVID-19 courses based on literature synthesis.

Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool.

The human immune response must continuously adapt to newly emerging SARS-CoV-2 variants. To investigate how B cells respond to repeated SARS-CoV-2 antigen exposure by Wu01 booster vaccination and Omicron breakthrough infection, we performed a molecular longitudinal analysis of the memory B cell pool. We demonstrate that a subsequent breakthrough infection substantially increases the frequency of B cells encoding SARS-CoV-2-neutralizing antibodies.

Single-cell analysis of memory B cells from top neutralizers reveals multiple sites of vulnerability within HCMV Trimer and Pentamer.

Human cytomegalovirus (HCMV) can cause severe diseases in fetuses, newborns, and immunocompromised individuals. Currently, no vaccines are approved, and treatment options are limited. Here, we analyzed the human B cell response of four HCMV top neutralizers from a cohort of 9,000 individuals.

Dynamics and durability of HIV-1 neutralization are determined by viral replication.

Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers-persons with HIV-1 who naturally develop broad and potent nAbs-can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART).

Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals.

HIV-1 broadly neutralizing antibodies (bNAbs) are able to suppress viremia and prevent infection. Their induction by vaccination is therefore a major goal. However, in contrast to antibodies that neutralize other pathogens, HIV-1-specific bNAbs frequently carry uncommon molecular characteristics that might prevent their induction.

Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa.

Drug-resistant Pseudomonas aeruginosa (PA) poses an emerging threat to human health with urgent need for alternative therapeutic approaches. Here, we deciphered the B cell and antibody response to the virulence-associated type III secretion system (T3SS) in a cohort of patients chronically infected with PA. Single-cell analytics revealed a diverse B cell receptor repertoire directed against the T3SS needle-tip protein PcrV, enabling the production of monoclonal antibodies (mAbs) abrogating T3SS-mediated cytotoxicity.

The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm.

The novel coronavirus pandemic, first reported in December 2019, was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells, which can elicit acute respiratory distress syndrome (ARDS) characterized by the rapid onset of widespread inflammation, the so-called cytokine storm. In response to viral infections, monocytes are recruited into the lung and subsequently differentiate into dendritic cells (DCs).