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We designed a protein biosensor that uses thermodynamic coupling for sensitive and rapid detection of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in serum. The biosensor is a switchable, caged luciferase-receptor-binding domain (RBD) construct that detects serum-antibody interference with the binding of virus RBD to angiotensin-converting enzyme 2 (ACE-2) as a proxy for neutralization. Our coupling approach does not require target modification and can better distinguish sample-to-sample differences in analyte binding affinity and abundance than traditional competition-based assays.
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http://dx.doi.org/10.1038/s41587-022-01280-8 | DOI Listing |
AAPS J
September 2025
Gene Transfer and Immunogenicity Branch, Division of Gene Therapy 2, Office of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, WO52 RM3124, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993-0002, USA.
As the field of gene therapy advances and as the importance of sex as a biological variable in shaping viral immune responses is recognized, the impact of sex on adeno-associated virus (AAV) vectors mediated gene therapies remain largely unexplored. Here we review current understanding of the immune response against AAV gene therapy as well as the knowledge of sex differences observed in viral responses. We discuss sex differences in innate immune mechanisms such as Toll-like receptor recognition and complement activation, as well as the functional responses of key immune cells such as dendritic cells, macrophages, and T/B cells that are involved in AAV immunogenicity.
View Article and Find Full Text PDFArch Virol
September 2025
State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 150069, Harbin, Heilongjiang, China.
Epizootic hemorrhagic disease virus (EHDV) causes severe disease in ruminants. We assessed the pathogenicity of the Chinese EHDV-7 isolate YN09 in mice lacking the type I interferon receptor and in sheep. In mice, YN09 infection resulted in 100% mortality, with histopathological lesions, viral replication, and immunoreactivity in multiple organs.
View Article and Find Full Text PDFVet Microbiol
September 2025
College of Animal Science and Technology/Laboratory of Functional Microbiology and Animal Health, Henan University of Science and Technology, Luoyang 471023, PR China; Luoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Henan University of Science and Techno
Bovine Viral Diarrhea Virus (BVDV) is a major pathogen associated with calf diarrhea and reproductive disorders in cattle. This study evaluated the immune-protective potential of a subunit vaccine based on the capsid C protein of the BVDV HNL-1 strain. In mice model, the C protein subunit vaccine exhibits a favorable safety and elicits robust immune-protective efficacy comparable to commercial inactivated vaccines.
View Article and Find Full Text PDFSci Adv
September 2025
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
Influenza A viruses remain a global health threat, yet no universal antibody therapy exists. Clinical programs have centered on neutralizing mAbs, only to be thwarted by strain specificity and rapid viral escape. We instead engineered three non-neutralizing IgG2a mAbs that target distinct, overlapping epitopes within the conserved N terminus of the M2 ectodomain (M2e).
View Article and Find Full Text PDFSci Transl Med
September 2025
Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
Hepatocyte apoptosis is a key feature of metabolic dysfunction-associated steatohepatitis (MASH), but the fate of apoptotic hepatocytes in MASH is poorly understood. Here, we explore the hypotheses that clearance of dead hepatocytes by liver macrophages (efferocytosis) is impaired in MASH because of low expression of the efferocytosis receptor T cell immunoglobulin and mucin domain containing 4 (TIM4; gene ) by MASH liver macrophages, which then drives liver fibrosis in MASH. We show that apoptotic hepatocytes accumulate in human and experimental MASH, using mice fed the fructose-palmitate-cholesterol (FPC) diet or the high-fat, choline-deficient amino acid-defined (HF-CDAA) diet.
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