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Designed mosaic nanoparticles enhance cross-reactive immune responses in mice.
Cell
January 2025
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA. Electronic address:
Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover of zoonotic sarbecoviruses into humans. Using a computational approach, we designed variants of SARS-CoV-2 RBDs and selected 7 natural sarbecovirus RBDs, each predicted to fold properly and abrogate antibody responses to variable epitopes. RBDs were attached to 60-mer nanoparticles to make immunogens displaying two (mosaic-2s), five (mosaic-5), or seven (mosaic-7) different RBDs for comparisons with mosaic-8b, which elicited cross-reactive antibodies and protected animals from sarbecovirus challenges.
View Article and Find Full Text PDFCross-reactive sarbecovirus antibodies induced by mosaic RBD-nanoparticles.
bioRxiv
January 2025
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Therapeutic monoclonal antibodies (mAbs) against SARS-CoV-2 become obsolete as spike substitutions reduce antibody binding. To induce antibodies against conserved receptor-binding domain (RBD) regions for protection against SARS-CoV-2 variants of concern and zoonotic sarbecoviruses, we developed mosaic-8b RBD-nanoparticles presenting eight sarbecovirus RBDs arranged randomly on a 60-mer nanoparticle. Mosaic-8b immunizations protected animals from challenges from viruses whose RBDs were matched or mismatched to those on nanoparticles.
View Article and Find Full Text PDFEndothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling.
Commun Biol
January 2025
Freie Universität Berlin, Institute for Chemistry and Biochemistry, Thielallee 63, 14195, Berlin, Germany.
Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs).
View Article and Find Full Text PDFSalicylic Acid-Induced Expression Profiles of LRR and LRR-RLK Candidate Genes Modulate Resistance in Blackgram and Its Two Wild Non-Progenitors.
Plants (Basel)
December 2024
Department of Genetics and Plant Breeding, Banda University of Agriculture and Technology, Banda 210 001, India.
Blackgram is an important short-duration grain legume, but its yield is highly affected by various stresses. Among biotic stresses, yellow mosaic disease (YMD) is known as a devastating disease that leads to 100% yield loss under severe conditions. The cultivated lines possess resistance, but exploring more diverse sources of resistance may be useful for pyramiding to improve the durability of said resistance.
View Article and Find Full Text PDFMHC-I proteins present epitopic peptides to CD8+ T cells to elicit multifaceted adaptive immune responses. The affinity and avidity of interactions between peptide-MHC molecules and T-cell receptors (TCR) are fundamental parameters that contribute to the induction of activated or anergic T cell states. Here, we present a loadable system, VLP-Open HLA, featuring a virus-like particle (VLP) that can accommodate up to 60 loadable HLA (HLA - human leukocyte antigen) molecules.
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