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Evans, David

Publications and source records attributed to Evans, David.

Isolation and characterization of IgG3 glycan-targeting antibodies with exceptional cross-reactivity for diverse viral families

Broadly reactive antibodies that target sequence-diverse antigens are of interest for vaccine design and monoclonal antibody therapeutic development because they can protect against multiple strains of a virus and provide a barrier to evolution of escape mutants. Using LIBRA-seq (linking B cell receptor to antigen specificity through sequencing) data for the B cell repertoire of an individual chronically infected with human immunodeficiency virus type 1 (HIV-1), we identified a lineage of IgG3 antibodies predicted to bind to HIV-1 Envelope (Env) and influenza A Hemagglutinin (HA). Two lineage members, antibodies 2526 and 546, were confirmed to bind to a large panel of diverse antigens, including several strains of HIV-1 Env, influenza HA, coronavirus (CoV) spike, hepatitis C virus (HCV) E protein, Nipah virus (NiV) F protein, and Langya virus (LayV) F protein. We found that both antibodies bind to complex glycans on the antigenic surfaces. Antibody 2526 targets the stem region of influenza HA and the N-terminal domain (NTD) region of SARS-CoV-2 spike. A crystal structure of 2526 Fab bound to mannose revealed the presence of a glycan-binding pocket on the light chain. Antibody 2526 cross-reacted with antigens from multiple pathogens and displayed no signs of autoreactivity. These features distinguish antibody 2526 from previously described glycan-reactive antibodies. Further study of this antibody class may aid in the selection and engineering of broadly reactive antibody therapeutics and can inform the development of effective vaccines with exceptional breadth of pathogen coverage.

Microbiology↗

Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire

The generation of broadly neutralizing antibodies (bnAbs) to conserved epitopes on HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The animal models commonly used for HIV do not reliably produce a potent broadly neutralizing serum antibody response, with the exception of cows. Cows have previously produced a CD4 binding site response by homologous prime and boosting with a native-like Env trimer. In small animal models, other engineered immunogens were shown to focus antibody responses to the bnAb V2-apex region of Env. Here, we immunized two groups of cows (n = 4) with two regimens of V2-apex focusing Env immunogens to investigate whether antibody responses could be generated to the V2-apex on Env. Group 1 was immunized with chimpanzee simian immunodeficiency virus (SIV)-Env trimer that shares its V2-apex with HIV, followed by immunization with C108, a V2-apex focusing immunogen, and finally boosted with a cross-clade native-like trimer cocktail. Group 2 was immunized with HIV C108 Env trimer followed by the same HIV trimer cocktail as Group 1. Longitudinal serum analysis showed that one cow in each group developed serum neutralizing antibody responses to the V2-apex. Eight and 11 bnAbs were isolated from Group 1 and Group 2 cows, respectively, and showed moderate breadth and potency. Potent and broad responses in this study developed much later than previous cow immunizations that elicited CD4bs bnAbs responses and required several different immunogens. All isolated bnAbs were derived from the ultralong CDRH3 repertoire. The finding that cow antibodies can target more than one broadly neutralizing epitope on the HIV surface reveals the generality of elongated structures for the recognition of highly glycosylated proteins. The exclusive isolation of ultralong CDRH3 bnAbs, despite only comprising a small percent of the cow repertoire, suggests these antibodies outcompete the long and short CDRH3 antibodies during the bnAb response.

Microbiology↗

Terrestrial Very-Long-Baseline Atom Interferometry: Workshop Summary

This document presents a summary of the 2023 Terrestrial Very-Long-Baseline Atom Interferometry Workshop hosted by CERN. The workshop brought together experts from around the world to discuss the exciting developments in large-scale atom interferometer (AI) prototypes and their potential for detecting ultralight dark matter and gravitational waves. The primary objective of the workshop was to lay the groundwork for an international TVLBAI proto-collaboration. This collaboration aims to unite researchers from different institutions to strategize and secure funding for terrestrial large-scale AI projects. The ultimate goal is to create a roadmap detailing the design and technology choices for one or more km-scale detectors, which will be operational in the mid-2030s. The key sections of this report present the physics case and technical challenges, together with a comprehensive overview of the discussions at the workshop together with the main conclusions.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

The DeepMIP Contribution to PMIP4: Experimental Design for Model Simulations of the EECO, PETM, and pre-PETM (version 1.0)

Past warm periods provide an opportunity to evaluate climate models under extreme forcing scenarios, in particular high ( greater than 800 ppmv) atmospheric CO2 concentrations. Although a post hoc intercomparison of Eocene (approximately 50 Ma) climate model simulations and geological data has been carried out previously, models of past high-CO2 periods have never been evaluated in a consistent framework. Here, we present an experimental design for climate model simulations of three warm periods within the early Eocene and the latest Paleocene (the EECO, PETM, and pre-PETM). Together with the CMIP6 pre-industrial control and abrupt 4(times) CO2 simulations, and additional sensitivity studies, these form the first phase of DeepMIP - the Deep-time Model Intercomparison Project, itself a group within the wider Paleoclimate Modeling Intercomparison Project (PMIP). The experimental design specifies and provides guidance on boundary conditions associated with palaeogeography, greenhouse gases, astronomical configuration, solar constant, land surface processes, and aerosols. Initial conditions, simulation length, and output variables are also specified. Finally, we explain how the geological data sets, which will be used to evaluate the simulations, will be developed.

climate models↗

Improving Post-Hurricane Katrina Forest Management with MODIS Time Series Products

Hurricane damage to forests can be severe, causing millions of dollars of timber damage and loss. To help mitigate loss, state agencies require information on location, intensity, and extent of damaged forests. NASA's MODerate Resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) time series data products offers a potential means for state agencies to monitor hurricane-induced forest damage and recovery across a broad region. In response, a project was conducted to produce and assess 250 meter forest disturbance and recovery maps for areas in southern Mississippi impacted by Hurricane Katrina. The products and capabilities from the project were compiled to aid work of the Mississippi Institute for Forest Inventory (MIFI). A series of NDVI change detection products were computed to assess hurricane induced damage and recovery. Hurricane-induced forest damage maps were derived by computing percent change between MODIS MOD13 16-day composited NDVI pre-hurricane "baseline" products (2003 and 2004) and post-hurricane NDVI products (2005). Recovery products were then computed in which post storm 2006, 2007, 2008 and 2009 NDVI data was each singularly compared to the historical baseline NDVI. All percent NDVI change considered the 16-day composite period of August 29 to September 13 for each year in the study. This provided percent change in the maximum NDVI for the 2 week period just after the hurricane event and for each subsequent anniversary through 2009, resulting in forest disturbance products for 2005 and recovery products for the following 4 years. These disturbance and recovery products were produced for the Mississippi Institute for Forest Inventory's (MIFI) Southeast Inventory District and also for the entire hurricane impact zone. MIFI forest inventory products were used as ground truth information for the project. Each NDVI percent change product was classified into 6 categories of forest disturbance intensity. Stand age and stand type raster data, also provided by MIFI, were used along with the forest disturbance/recovery products to create forest damage stratification products integrating 3 stand type classes, 6 stand age classes, and 6 forest disturbance intensity classes. This stratification product will be used to aid MIFI timber inventory planning and to prepare for damage assessments due to future hurricane events. Validation of MODIS percent NDVI change products was performed by comparing the MODIS percent NDVI change products to those from Landsat data for the same time and MIFI inventory district area.

Lewis, Mark David↗

Source Determination for Substorm-Related Ion Injections

The grant supported an effort to restore and analyze data from the Spacecraft Charging at High Altitude (SCATHA) spacecraft. This spacecraft, which was originally an Air Force mission, was launched into a near geo-synchronous orbit in early 1979 to, investigate the inner magnetosphere at altitudes where it was known that spacecraft can undergo significant charging events. SCATHA included an ion composition experiment (designated SC8) and in many ways was a precursor to other missions, such as the AMPTE Charge Composition Explorer.

Strangeway, Robert J.↗

Investigation of the Transport of Solar Ions Through the Earth's Magnetosphere

The objective of this study has been to infer, by statistical means, the most probable mode of entry of solar wind plasma into Earth's magnetotail, using a particular set of archived data from the Lockheed Plasma Composition Experiment on the International Sun-Earth Explorer One (ISEE-1) satellite, jointly sponsored by the National Aeronautics and Space Administration (NASA) and the European Space Agency (ESA) in the 1970's and 80's. Despite their considerable age, the Lockheed ISEE-1 data are still, at the time of this report, the only substantial ion composition data in the sub-keV to keV energy range available from the magnetotail beyond 9 R(sub E), because of various technical problems with ion mass spectrometers on later missions, and are therefore a unique source of information about the mixing of solar and terrestrial origin plasmas in the tail, within the ISEE-1 apogee of almost 23 R(sub E). The entire set of archived data used in this study, covering the 4.5 years of operation of the instrument and comprising not only tail measurements but also data from the inner magnetosphere as well as data from outside the magnetopause, is now available to the public via the WorldWideWeb at the address: http://cis.spasci.com/ISEE_ions The fundamental assumption of this and other studies of magnetosphere ion composition is that He++ and O+ ions are virtually certain "tags" of solar and terrestrial origins, respectively. This is an assumption with strong theoretical basis and it is corroborated by observational evidence, including the often substantial differences between the velocity distribution functions of those two species. The H+ ions can have a dual origin, in principle, but the close resemblance in the ISEE-1 data between the dynamics of H+ and He++ ions indicates a predominantly solar origin of the H+ ions in the tail, at least. By the same token, the usually minor He+ ions are probably almost entirely of terrestrial origin, because of their similarity to the O+ ions.

Lennartsson, O. W.↗