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Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity.
Nat Commun
January 2025
Institute of Virology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation in vitro, but their role in infection and pathogenesis is unknown. To examine their in vivo function in an animal model evolutionarily closely related to humans, we identified and characterized Rh05, Rh152/151 and Rh173 as the complete set of vFcγRs encoded by rhesus CMV (RhCMV). Each one of these proteins displays functional similarities to their prospective HCMV orthologs with respect to antagonizing host FcγR activation in vitro.
View Article and Find Full Text PDFBlocking the CD39/CD73 pathway synergizes with anti-CD20 bispecific antibody in nodal B-cell lymphoma.
J Immunother Cancer
January 2025
Heidelberg University Hospital Department of Hematology Oncology and Rheumatology, Heidelberg, Germany
Bispecific antibodies (BsAb) have emerged as a leading treatment modality in patients suffering from B-cell non-Hodgkin's lymphoma (B-NHL). However, treatment failure is common and may potentially be attributed to pre-existing or emerging T-cell exhaustion. CD39 catalyzes-together with CD73-the hydrolysis of immunogenic ATP into immunosuppressive adenosine and thus actively promotes an immunosuppressive micromilieu.
View Article and Find Full Text PDFA comprehensive benchmarking for evaluating TCR embeddings in modeling TCR-epitope interactions.
Brief Bioinform
November 2024
Department of Computer Science, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Hong Kong, 999077, China.
The complexity of T cell receptor (TCR) sequences, particularly within the complementarity-determining region 3 (CDR3), requires efficient embedding methods for applying machine learning to immunology. While various TCR CDR3 embedding strategies have been proposed, the absence of their systematic evaluations created perplexity in the community. Here, we extracted CDR3 embedding models from 19 existing methods and benchmarked these models with four curated datasets by accessing their impact on the performance of TCR downstream tasks, including TCR-epitope binding affinity prediction, epitope-specific TCR identification, TCR clustering, and visualization analysis.
View Article and Find Full Text PDFMulticentre adaptive randomised trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin versus calcineurin inhibitor-based or sirolimus-based post-transplant cyclophosphamide (Methods of T cell Depletion, MoTD trial).
BMJ Open
January 2025
Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK.
Introduction: Graft-versus-host disease (GvHD) remains a major complication of allogeneic stem cell transplantation (allo-SCT), affecting 30-70% of patients (representing 800 new patients per year in the UK). The risk is higher in patients undergoing unrelated allo-SCT. About 1 in 10 patients die as a result of GvHD or through complications of its treatment.
View Article and Find Full Text PDFReplication-incompetent VSV-based vaccine elicits protective responses against SARS-CoV-2 and influenza virus.
Sci Adv
January 2025
Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses lead to severe respiratory illnesses and death in humans, exacerbated in individuals with underlying health conditions, remaining substantial global public health concerns. Here, we developed a bivalent replication-incompetent single-cycle pseudotyped vesicular stomatitis virus vaccine that incorporates both a prefusion-stabilized SARS-CoV-2 spike protein lacking a furin cleavage site and a full-length influenza A virus neuraminidase protein. Vaccination of K18-hACE2 or C57BL/6J mouse models generated durable levels of neutralizing antibodies, T cell responses, and protection from morbidity and mortality upon challenge with either virus.
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