Monoclonal Antibodies to Meningococcal Factor H Binding Protein with Overlapping Epitopes and Discordant Functional Activity

Background: Meningococcal factor H binding protein (fHbp) is a promising vaccine candidate. Anti-fHbp antibodies can bind to meningococci and elicit complement-mediated bactericidal activity directly. The antibodies also can block binding of the human complement down-regulator, factor H (fH). Without bound fH, the organism would be expected to have increased susceptibility to bacteriolysis. Here we describe bactericidal activity of two anti-fHbp mAbs with overlapping epitopes in relation to their different effects on fH binding and bactericidal activity. Methods and Principal Findings: Both mAbs recognized prevalent fHbp sequence variants in variant group 1. Using yeast display and site-specific mutagenesis, binding of one of the mAbs (JAR 1, IgG3) to fHbp was eliminated by a single amino acid substitution, R204A, and was decreased by K143A but not by R204H or D142A. The JAR 1 epitope overlapped that of previously described mAb (mAb502, IgG2a) whose binding to fHbp was eliminated by R204A or R204H substitutions, and was decreased by D142A but not by K143A. Although JAR 1 and mAb502 appeared to have overlapping epitopes, only JAR 1 inhibited binding of fH to fHbp and had human complement-mediated bactericidal activity. mAb502 enhanced fH binding and lacked human complement-mediated bactericidal activity. To control for confounding effects of different mouse IgG subclasses on complement activation, we created chimeric mAbs in which the mouse mAb502 or JAR 1 paratopes were paired with human IgG1 constant regions. While both chimeric mAbs showed similar binding to fHbp, only JAR 1, whic

Expanding the Paradigms of Plant Pathogen Life History and Evolution of Parasitic Fitness beyond Agricultural Boundaries

International audienc

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05-1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4-7 days or ≥ 8 days of 1.25 (1.04-1.48), p = 0.015 and 1.31 (1.11-1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care

Ligand-bridged charge extraction and enhanced quantum efficiency enable efficient n-i-p perovskite/silicon tandem solar cells

Translating the high power conversion efficiencies of single-junction perovskite solar cells in their classic, non-inverted (n-i-p) architecture to efficient monolithic n-i-p perovskite/silicon tandem solar cells with high current densities has been a persistent challenge due to the lack of low-temperature processable, chemically-insoluble contact materials with appropriate polarity and sufficient optical transparency. To address this, we developed sputtered amorphous niobium oxide (a-NbOx) with ligand-bridged C-60 as an efficient electron-selective contact, deposited on the textured-silicon bottom cell. For the sunward, hole-selective contact we implemented a stack of molecularly doped broadband transparent evaporated 2,2 ',7,7 '-tetra(N,N-di-p-tolyl)amino-9,9-spirobifluorene (spiro-TTB) and atomic layer deposited vanadium oxide, which further enhances the device quantum efficiency. Combining these contact materials with two-dimensional perovskite passivation on the micrometer-thick solution-processed perovskite top cell yields 27% efficient monolithic n-i-p perovskite/silicon tandem solar cells, which represents one of the highest power conversion efficiencies reported on pyramidal textured crystalline silicon bottom cells, and the highest with this polarity.The authors would like to thanks to Nini Wei for the TEM images; funding: the research reported in this publication was supported by funding from King Abdullah University of Science and Technology (KAUST) under award no. OSR-CARF/CCF-3079 and award no. IED OSR-2019-4208