n 111) and contacts (
K and
L) The normalized AUC of anti-RBD IgA (K) or IgG (L) ELISA for patients with gastrointestinal (GI) symptoms (
n 32) and without GI symptoms (
n 117) was plotted. The
r and
P values for the correlations in (C) to (G) were determined by two-tailed Spearman’s correlations. For (H) to (L), horizontal bars indicate median values. Statistical significance was determined using a two-tailed Mann-Whitney
U test.
P 0.005) and severity of symptoms (
P 0.0001) but not timing of sample collection relative to onset (
P 0.69) or age (
P 0.22) (Fig. 1, C to F). Concentrations of anti-RBD IgA antibodies correlated strongly with anti-RBD IgG concentrations (
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A shared Toll for innate immunity
Toll-like receptor 2 (TLR2) is found in various tissues but is best known for its role in the innate immune system of activating sentinel immune cells in response to infection. Using conditional knockout mice, McCoy
et al. found that TLR2 also mediated innate immune signaling within the endothelium. TLR2 in endothelial cells activated proinflammatory signaling that promoted angiogenesis and immune cell recruitment in response to various “danger” signals, such as those produced during infection or tissue damage. Endothelial TLR2 also supported tumor growth in a mouse model of prostate cancer. These findings show that the endothelium contributes to innate immune responses and that TLR2 may be a therapeutic target in cancer (see also the Focus by Mahfoud and Petrova).
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread with devastating consequences. For passive immunization efforts, nanobodies have size and cost advantages over conventional antibodies. Here, we generated four neutralizing nanobodies that target the receptor-binding domain of the SARS-CoV-2 spike protein. We defined two distinct binding epitopes using x-ray crystallography and cryo-electron microscopy. Based on the structures, we engineered multivalent nanobodies with more than 100-fold improved neutralizing activity than monovalent nanobodies. Biparatopic nanobody fusions suppressed the emergence of escape mutants. Several nanobody constructs neutralized through receptor-binding competition, while other monovalent and biparatopic nanobodies triggered aberrant activation of the spike fusion machinery. These premature conformational changes in the spike protein forestalled productive fusion, and rendered the virions non-infectious.
Expert Insight: Compliance-ready intact mass analysis of modified oligonucleotides and impurities using the BioAccord LC-MS System
Watch this on-demand webinar to learn how the BioAccord LC-MS system delivers robust UPLC separations performance for a range of modified oligos
06 Jan 2021
Dr. Catalin Doneanu, Principal Chemist at Waters
As the pipeline for oligonucleotide-based therapeutics continues to grow, with over 300 currently in clinical trials, along with an increased demand for GMP/GLP-validated oligonucleotide reagents (including primers, probes, gRNA) for clinical DNA testing and sequencing, the need for robust, compliance-ready LC-MS analysis of oligonucleotides has never been greater.
Waters has designed the BioAccord LC-MS System to deliver robust, reproducible separations and accurate mass performance in a compact, easy-to-use format, one that facilitates deployment across regulated development, manufacturing and QC labs and supports a range of routine biopharmaceut