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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 955 records · Page 53
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

SNF Data Visualization on the Centralized Used Fuel Resource for Information Exchange (CURIE) Website

To better inform stakeholders regarding the nature of spent nuclear fuel (SNF) at utility sites, an online data visualization system has been created for the U.S. Department of Energy's Office of Nuclear Energy (DOENE). The data visualization system is part of the Centralized Used Fuel Resource for Information Exchange (CURIE) website, hosted by the Oak Ridge National Laboratory (ORNL) for DOE-NE. The visualization employs a database that is part of an analysis tool known as the Used Nuclear Fuel Storage, Transportation and Disposal Analysis Resource and Data System (UNF-ST[and]DARDS). Because many of the previous document management and sharing tools related to SNF have been terminated (or are inaccessible), a new tool, the CURIE, was developed for DOE-NE and launched on March 1, 2013 at http://curie.ornl.gov. In addition to supporting DOE SNF programs, CURIE is a national resource that is accessible to industry, vendor, federal, and laboratory partners, as well as other stakeholders. CURIE's architecture was initially based on previous work that supported DOE's Bioenergy Technologies Office on the Bioenergy Knowledge Discovery Framework (KDF). The site uses an open-source search engine, Apache Solr, which provides intuitive search results based on a faceted search method similar to that used by Amazon.com{sup R}. This algorithm helps to ensure that finding documents and data is straightforward. SNF data visualization capability was added to the CURIE website which provides a capability to post and access documents and data related to the management of SNF. CURIE currently maintains over 4,100 documents and the Siting Experience Database (SED), which was developed in response to a near-term recommendation by the Blue Ribbon Commission on America's Nuclear Future (BRC). The SED is a database of the experience that has been gained and relevant documentation that has been produced in efforts to site nuclear waste facilities, both in the US and abroad. Most of these documents are publicly accessible. In addition, CURIE maintains a current calendar of related events, an SNF image gallery, featured documents, and external links to related databases and websites. CURIE also maintains private groups (or communities) to facilitate collaborative development through sharing and editing documents that are not publicly available. There are more than 250 registered users in 23 different communities within CURIE.ORNL has also been developing UNF-ST[and]DARDS to provide a controlled source of technical data for various waste management system analysis/evaluation tools, access to key technical data, and analysis capabilities for characterizing the SNF inventory. UNF-ST[and]DARDS also provides enhanced capabilities to assess safety, risk, and uncertainty throughout the integrated waste management system. This paper describes the UNF-ST[and]DARDS data available for visualization and the associated visualization techniques used by CURIE to display this data.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2016

Response of the tropical Pacific Ocean to El Niño versus global warming

Climate models project an El Niño-like SST response in the tropical Pacific Ocean to global warming (GW). By employing the Community Earth System Model (CESM) and applying an overriding technique to its ocean component, Parallel Ocean Program version 2 (POP2), this study investigates the similarity and difference of formation mechanism for the changes in the tropical Pacific Ocean under El Niño and GW. Results show that, despite sharing some similarities between the two scenarios, there are many significant distinctions between GW and El Niño: 1) the phase locking of the seasonal cycle reduction is more notable under GW compared with El Niño, implying more extreme El Niño events in the future; 2) in contrast to the penetration of the equatorial subsurface temperature anomaly that appears to propagate in the form of an oceanic equatorial upwelling Kelvin wave during El Niño, the GW-induced subsurface temperature anomaly manifest in the form of off-equatorial upwelling Rossby waves; 3) while significant across-equator northward heat transport (NHT) is induced by the wind stress anomalies associated with El Niño, little NHT is found at the equator due to a symmetric change in the shallow meridional overturning circulation that appears to be weakened in both North and South Pacific under GW; and 4) the maintaining mechanisms for the eastern equatorial Pacific warming are also substantially different.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Rab7 empowers renal tubular epithelial cells with autophagy-mediated protection against albumin-induced injury

Most patients with chronic kidney disease (CKD) present with proteinuria and extracellular matrix (ECM) deposition in the interstitium. Matrix metalloproteinase-2 (MMP-2) is important for maintaining ECM metabolism and it affects the formation and development of CKD. Autophagy has been reported to be protective against renal tubular injury, but the role of autophagy related to ECM metabolism is unclear. Rab7 is a shared molecule of endocytosis and autophagy. The aim of this study is to explore the role of autophagy in regulating MMP-2 activity and to determine whether Rab7 functions in regulating MMP-2 activity and injury in albumin-overloaded TECs. In this study, abovine serum albumin (BSA)-overload rat model was first established and collagen deposition and deficient autophagic response were observed in vivo, and stimulation with albumin nanoparticles resulted in MMP-2 overactivation and obstructed autophagic flux induced by lysosomal dysfunction in vitro. Furthermore, overactivation of MMP-2 was mediated by its related regulatory molecules such as membrane-type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinase-2 (TIMP-2) and reversion-inducing-cysteine-rich protein with kazal motifs (RECK) on the membrane of TECs (HK-2 cellline). After up-regulating Rab7, albumin-induced MMP-2 overactivation was attenuated, which was reversed by chloroquine (CQ; an endocytosis inhibitor). In addition, our data indicated that up-regulation of Rab7 relieved epithelial-mesenchymal transition (EMT) and apoptosis in albumin-treated TECs. Taken together, our study demonstrated that autophagy regulates MMP-2 activity in a Rab7-dependent manner. Thus, Rab7 is a newly developed target for protecting TECs from albumin-induced injury.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Multi-omic elucidation of aromatic catabolism in adaptively evolved Rhodococcus opacus

Lignin utilization has been identified as a key factor in biorefinery profitability. However, lignin depolymerization generates heterogeneous aromatic mixtures that inhibit microbial growth and conversion of lignocellulose to biochemicals. Rhodococcus opacus is a promising aromatic-catabolizing, oleaginous bacterium, but mechanisms for its aromatic tolerance and utilization remain undercharacterized. To better understand these mechanisms, we adaptively evolved R. opacus for improved utilization of 32 combinations of diverse aromatic compounds. Evolved R. opacus mutants showed up to 1900% growth improvement in the utilization of phenol, guaiacol, 4-hydroxybenzoate, vanillate, and benzoate compared to the wild-type strain. Whole genome sequencing revealed several redox-related genes with mutations shared across multiple adapted mutants. PVHG6, the mutant with the most improved growth on a mixture of multiple aromatic compounds, showed 56% lower superoxide dismutase activity than the wild-type strain, suggesting that redox reactions are important for aromatic tolerance and utilization. Comparative transcriptomics revealed by-product detoxification pathways and five aromatic funneling pathways that were upregulated in response to specific aromatic compounds. Gene knockout experiments confirmed the two degradation routes of the β-ketoadipate pathway for five aromatic compounds. Finally, these results provide an improved understanding of aromatic bioconversion and facilitate development of R. opacus as a biorefinery host.

09 BIOMASS FUELS↗
DOE OSTI2022

Differentially Private Synthesis and Sharing of Network Data Via Bayesian Exponential Random Graph Models

Abstract Network data often contain sensitive relational information. One approach to protecting sensitive information while offering flexibility for network analysis is to share synthesized networks based on the information in originally observed networks. We employ differential privacy (DP) and exponential random graph models (ERGMs) and propose the DP-ERGM method to synthesize network data. We apply DP-ERGM to two real-world networks. We then compare the utility of synthesized networks generated by DP-ERGM, the DyadWise Randomized Response (DWRR) approach, and the Synthesis through Conditional distribution of Edge given nodal Attribute (SCEA) approach. In general, the results suggest that DP-ERGM preserves the original information significantly better than two other approaches in network structural statistics and inference for ERGMs and latent space models. Furthermore, DP-ERGM satisfies node DP through modeling the global network structure with ERGM, a stronger notion of privacy than the edge DP under which DWRR and SCEA operate.

graph synthesis↗
DOE OSTI2016

SU-F-P-10: A Web-Based Radiation Safety Relational Database Module for Regulatory Compliance

Purpose: Maintaining compliance with Radioactive Materials Licenses is inherently a time-consuming task requiring focus and attention to detail. Staff tasked with these responsibilities, such as the Radiation Safety Officer and associated personnel must retain disparate records for eventual placement into one or more annual reports. Entering results and records in a relational database using a web browser as the interface, and storing that data in a cloud-based storage site, removes procedural barriers. The data becomes more adaptable for mining and sharing. Methods: Web-based code was written utilizing the web framework Django, written in Python. Additionally, the application utilizes JavaScript for front-end interaction, SQL, HTML and CSS. Quality assurance code testing is performed in a sequential style, and new code is only added after the successful testing of the previous goals. Separate sections of the module include data entry and analysis for audits, surveys, quality management, and continuous quality improvement. Data elements can be adapted for quarterly and annual reporting, and for immediate notification of user determined alarm settings. Results: Current advances are focusing on user interface issues, and determining the simplest manner by which to teach the user to build query forms. One solution has been to prepare library documents that a user can select or edit in place of creation a new document. Forms are being developed based upon Nuclear Regulatory Commission federal code, and will be expanded to include State Regulations. Conclusion: Establishing a secure website to act as the portal for data entry, storage and manipulation can lead to added efficiencies for a Radiation Safety Program. Access to multiple databases can lead to mining for big data programs, and for determining safety issues before they occur. Overcoming web programming challenges, a category that includes mathematical handling, is providing challenges that are being overcome.

61 RADIATION PROTECTION AND DOSIMETRY↗
NASA NTRS1999

Visual- and Vestibular-Autonomic Influence on Short-Term Cardiovascular Regulatory Mechanisms

This synergy project was a one-year effort conducted cooperatively by members of the NSBRI Cardiovascular Alterations and Neurovestibular Adaptation Teams in collaboration with NASA Johnson Space Center (JSC) colleagues. The objective of this study was to evaluate visual autonomic interactions on short-term cardiovascular regulatory mechanisms. Based on established visual-vestibular and vestibular-autonomic shared neural pathways, we hypothesized that visually induced changes in orientation will trigger autonomic cardiovascular reflexes. A second objective was to compare baroreflex changes during postural changes as measured with the new Cardiovascular System Identification (CSI) technique with those measured using a neck barocuff. While the neck barocuff stimulates only the carotid baroreceptors, CSI provides a measure of overall baroreflex responsiveness. This study involved a repeated measures design with 16 healthy human subjects (8 M, 8 F) to examine cardiovascular regulatory responses during actual and virtual head-upright tilts. Baroreflex sensitivity was first evaluated with subjects in supine and upright positions during actual tilt-table testing using both neck barocuff and CSI methods. The responses to actual tilts during this first session were then compared to responses during visually induced tilt and/or rotation obtained during a second session.

Mullen, Thomas J.↗
NASA NTRS2009

Internet Protocol Display Sharing Solution for Mission Control Center Video System

With the advent of broadcast television as a constant source of information throughout the NASA manned space flight Mission Control Center (MCC) at the Johnson Space Center (JSC), the current Video Transport System (VTS) characteristics provides the ability to visually enhance real-time applications as a broadcast channel that decision making flight controllers come to rely on, but can be difficult to maintain and costly. The Operations Technology Facility (OTF) of the Mission Operations Facility Division (MOFD) has been tasked to provide insight to new innovative technological solutions for the MCC environment focusing on alternative architectures for a VTS. New technology will be provided to enable sharing of all imagery from one specific computer display, better known as Display Sharing (DS), to other computer displays and display systems such as; large projector systems, flight control rooms, and back supporting rooms throughout the facilities and other offsite centers using IP networks. It has been stated that Internet Protocol (IP) applications are easily readied to substitute for the current visual architecture, but quality and speed may need to be forfeited for reducing cost and maintainability. Although the IP infrastructure can support many technologies, the simple task of sharing ones computer display can be rather clumsy and difficult to configure and manage to the many operators and products. The DS process shall invest in collectively automating the sharing of images while focusing on such characteristics as; managing bandwidth, encrypting security measures, synchronizing disconnections from loss of signal / loss of acquisitions, performance latency, and provide functions like, scalability, multi-sharing, ease of initial integration / sustained configuration, integration with video adjustments packages, collaborative tools, host / recipient controllability, and the utmost paramount priority, an enterprise solution that provides ownership to the whole process, while maintaining the integrity of the latest technological displayed image devices. This study will provide insights to the many possibilities that can be filtered down to a harmoniously responsive product that can be used in today's MCC environment.

Brown, Michael A.↗
DOE OSTI2020

Measuring Mobility Potential: A Novel Metric to Quantify Mobility Energy Productivity (MEP) of Transportation Systems

For nearly a century, the automobile has been the primary mode of personal transportation in American life. This remains true today as millions of people rely heavily on cars to connect suburbs with cities or to travel long distances - often out of routine or convenience. However, advances in technology are fueling an era of transportation transformation, with the potential to transform a system that has remained virtually unchanged for decades. The challenges of interconnecting our cities and creating a cross-continental transportation system for military purposes spawned the interstate highway system, generating the age of the automobile. In this century, congestion and mobility challenges of rising urban populations are spawning ever-evolving mobility and communications technologies to connect people to goods, services, and employment within a metropolitan and national context - all of which define a high quality of life. Aspiring smart cities are wrestling with questions such as: How does mobility impact a person's quality of life? Would people make different travel choices if they were presented with better information about their mobility options? Would businesses make different location decisions if they could assess the quality of mobility in that area? The ability to quantify the quality of mobility at a given location is the first step toward answering these questions. In response, an interdisciplinary team at the National Renewable Energy Laboratory (NREL) has developed the Mobility-Energy Productivity (MEP) metric. The MEP metric provides an avenue to not only measure the quality of mobility at a specific location in its current configuration, but also to test how various technological advances (e.g., connected and automated vehicles, plug-in electric vehicles, shared mobility) and infrastructure investments (e.g., building an additional highway lane, constructing a new shopping mall, implementing a transit-oriented development) impact the mobility of that location over time.

30 DIRECT ENERGY CONVERSION↗
NASA NTRS1994

Parallel Computing for Probabilistic Response Analysis of High Temperature Composites

The objective of this Phase I research was to establish the required software and hardware strategies to achieve large scale parallelism in solving PCM problems. To meet this objective, several investigations were conducted. First, we identified the multiple levels of parallelism in PCM and the computational strategies to exploit these parallelisms. Next, several software and hardware efficiency investigations were conducted. These involved the use of three different parallel programming paradigms and solution of two example problems on both a shared-memory multiprocessor and a distributed-memory network of workstations.

Sues, R. H.↗
DOE OSTI2022

The bright frontiers of microbial metabolic optogenetics

In recent years, light-responsive systems from the field of optogenetics have been applied to several areas of metabolic engineering with remarkable success. By taking advantage of light's high tunability, reversibility, and orthogonality to host endogenous processes, optogenetic systems have enabled unprecedented dynamical controls of microbial fermentations for chemical production, metabolic flux analysis, and population compositions in co-cultures. In this article, we share our opinions on the current state of this new field of metabolic optogenetics. Furthermore, we make the case that it will continue to impact metabolic engineering in increasingly new directions, with the potential to challenge existing paradigms for metabolic pathway and strain optimization as well as bioreactor operation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2011

Structural and magnetic characterization of BiFe{sub x}Mn{sub 2-x}O{sub 5} oxides (x=0.5, 1.0)

The title compounds have been synthesized by a citrate technique followed by thermal treatments in air (BiFe{sub 0.5}Mn{sub 1.5}O{sub 5}) or under high oxygen pressure conditions (BiFeMnO{sub 5}), and characterized by X-ray diffraction (XRD), neutron powder diffraction (NPD) and magnetization measurements. The crystal structures have been refined from NPD data in the space group Pbam at 295 K. These phases are isostructural with RMn{sub 2}O{sub 5} oxides (R=rare earths) and contain infinite chains of Mn{sup 4+}O{sub 6} octahedra sharing edges, linked together by (Fe,Mn){sup 3+}O{sub 5} pyramids and BiO{sub 8} units. These units are strongly distorted with respect to those observed in other RFeMnO{sub 5} compounds, due to the presence of the electronic lone pair on Bi{sup 3+}. It is noteworthy the certain level of antisite disorder exhibited in both samples, where the octahedral positions are partially occupied by Fe cations, and vice versa. BiFe{sub x}Mn{sub 2-x}O{sub 5} (x=0.5, 1.0) are short-range magnetically ordered below 20 K for x=0.5 and at 40 K for x=1.0. The main magnetic interactions seem to be antiferromagnetic (AFM); however, the presence of a small hysteresis in the magnetization cycles indicates the presence of some weak ferromagnetic (FM) interactions. - Graphical Abstract: BiFe{sub x}Mn{sub 2-x}O{sub 5} (x=0.5, 1.0) samples are isostructural with BiMn{sub 2}O{sub 5}, belonging to the Pbam space group. The crystal structure contains infinite chains of edge-sharing Mn{sup 4+}O{sub 6} octahedra, interconnected by dimer units of Fe{sup 3+}O{sub 5} square pyramids. These units are strongly distorted due to the presence of the electronic lone pair on Bi{sup 3+}. They are magnetically ordered at low temperatures. The main magnetic interactions seem to be antiferromagnetic with the presence of some weak ferromagnetic response. Highlights: > Two new compounds of formula BiFe{sub x}Mn{sub 2-x}O{sub 5} (x=0.5, 1.0) have been obtained. > Their crystallographic structure is isotypical with that of RMn{sub 2}O{sub 5} materials. > The presence of the electronic lone pair on Bi{sup 3+} severely distorts the crystal structure. > There is no establishment of a long-range ferrimagnetic structure.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

Determination of battery stability with advanced diagnostics.

Lithium ion batteries for use in battery electric vehicles (BEVs) has seen considerable expansion over the last several years. It is expected that market share and the total number of BEVs will continue to increase over coming years and that there will be changes in the environmental and use conditions for BEV batteries. Specifically aging of the batteries and exposure to an increased number of crash conditions presents a distinct possibility that batteries may be in an unknown state posing danger to the operator, emergency response personnel and other support personnel. The present work expands on earlier efforts to explore the ability to rapidly monitor using impedance spectroscopy techniques and characterize the state of different battery systems during both typical operations and under abusive conditions. The work has found that it is possible to detect key changes in performance for strings of up to four cells in both series and parallel configurations for both typical and abusive response. As a method the sensitivity for detecting change is enhanced for series configurations. For parallel configurations distinct changes are more difficult to ascertain, but under abusive conditions and for key frequencies it is feasible to use current rapid impedance techniques to identify change. The work has also found it feasible to use rapid impedance as an evaluation method for underload conditions, especially for series strings of cells.

25 ENERGY STORAGE↗
DOE OSTI2026

Coordinated Natural Gas and Electric Planning: Case Studies of Current Approaches and Practices

This paper examines how natural gas and electric utilities across eight U.S. states and two Canadian provinces are beginning to coordinate historically separate planning processes in response to growing system interdependencies, policy mandates, aging infrastructure, and changing customer energy choices. Electricity planning has long relied on robust integrated resource planning frameworks that weigh numerous objectives, risks, and costs. Natural gas planning, on the other hand, is typically less transparent and more narrowly focused on safety and system integrity. As economic, reliability, and policy drivers place new and shared demands on both systems, jurisdictions and utilities are experimenting with approaches such as coordinated forecasting, non pipeline alternatives, and combined planning pilots. A few have issued regulatory or statutory directives for greater data sharing and methodological alignment. Case studies from British Columbia, California, Colorado, Illinois, Massachusetts, Minnesota, New York, Québec, Rhode Island, and Washington illustrate a wide range of approaches to rethinking siloed planning. The paper identifies several common themes across the jurisdictions examined. It provides observations on the methods, processes, and organizational steps that may be needed in the future to address the challenges being faced by states and utilities. Lastly, it identifies some initial steps that states and utilities can consider if they would like to pursue more integrated, cost-effective, policy-aligned energy system planning.

03 NATURAL GAS↗
NASA NTRS2024

Landslide Hazard is Projected to Increase Across High Mountain Asia

High Mountain Asia has long been known as a hotspot for landslide risk, and studies have suggested that landslide hazard is likely to increase in this region over the coming decades. Extreme precipitation may become more frequent, with a nonlinear response relative to increasing global temperatures. However, these changes are geographically varied. This article maps probable changes to landslide hazard, as shown by a landslide hazard indicator (LHI) derived from downscaled precipitation and temperature. In order to capture the nonlinear response of slopes to extreme precipitation, a simple machine-learning model was trained on a database of landslides across High Mountain Asia to develop a regional LHI. This model was applied to statistically downscaled data from the 30 members of the Seamless System for Prediction and Earth System Research large ensembles to produce a range of possible outcomes under the Shared Socioeconomic Pathways 2-4.5 and 5-8.5. The LHI reveals that landslide hazard will increase in most parts of High Mountain Asia. Absolute increases will be highest in already hazardous areas such as the Central Himalaya, but relative change is greatest on the Tibetan Plateau. Even in regions where landslide hazard declines by year 2100, it will increase prior to the mid-century mark. However, the seasonal cycle of landslide occurrence will not change greatly across High Mountain Asia. Although substantial uncertainty remains in these projections, the overall direction of change seems reliable. These findings highlight the importance of continued analysis to inform disaster risk reduction strategies for stakeholders across High Mountain Asia.

Thomas A Stanley↗
DOE OSTI2019

Panel Session 81: Engaging on Safety at the Work Face - Workers, Front Line Managers, and Subcontractors

This panel focuses on engaging on safety at the work face, with the people who are there every day. This panel will discuss management approaches deployed to directly engage internal and subcontracted workers that have delivered measurable improvements in safety performance and culture. The panelists will share what they did that worked and their perspectives on why. About 24 to 30 people were in attendance. All statements below are paraphrased by the panel reporter and should not be considered direct quotes by the panelists. Presentations proposed include: 1 - Engaging on Safety at the Work Face: Workers, Front Line Managers, and Subcontractors (Jan Preston, Fluor Corporation (USA)); 2 - Responsibility for Safety: Workers and Line Management Joining Together to Improve Performance (Cynthia Williams, Canadian Nuclear Laboratories (Canada)); 3 - Worker Involvement: Trust and the Processing of the Remediated Nitrate Salts (David Funk, Los Alamos National Laboratory (USA)); 4 - Safety Culture: How Employee Engagement is Transforming the Paducah Site (Myrna Espinosa Redfield, Four Rivers Nuclear Partnership (USA)); 5 - Hazard Identification and Control: Subcontractor Performance, Oversight, and Continuous Improvement (Clint Wolfley, URS/CH2M Oak Ridge - UCOR (USA)); 6 - Managing Safety Performance Through Change (Alice Doswell, Fluor (USA))

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2022

Structural and dynamic mechanisms of GABA A receptor modulators with opposing activities

γ-Aminobutyric acid type A (GABA A ) receptors are pentameric ligand-gated ion channels abundant in the central nervous system and are prolific drug targets for treating anxiety, sleep disorders and epilepsy. Diverse small molecules exert a spectrum of effects on γ-aminobutyric acid type A (GABA A ) receptors by acting at the classical benzodiazepine site. They can potentiate the response to GABA, attenuate channel activity, or counteract modulation by other ligands. Structural mechanisms underlying the actions of these drugs are not fully understood. Here we present two high-resolution structures of GABA A receptors in complex with zolpidem, a positive allosteric modulator and heavily prescribed hypnotic, and DMCM, a negative allosteric modulator with convulsant and anxiogenic properties. These two drugs share the extracellular benzodiazepine site at the α/γ subunit interface and two transmembrane sites at β/α interfaces. Structural analyses reveal a basis for the subtype selectivity of zolpidem that underlies its clinical success. Molecular dynamics simulations provide insight into how DMCM switches from a negative to a positive modulator as a function of binding site occupancy. Together, these findings expand our understanding of how GABA A receptor allosteric modulators acting through a common site can have diverging activities.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

The human naive B cell repertoire contains distinct subclasses for a germline-targeting HIV-1 vaccine immunogen

Traditional vaccine development to prevent some of the worst current pandemic diseases has been unsuccessful so far. Germline-targeting immunogens have potential to prime protective antibodies (Abs) via more targeted immune responses. Success of germline-targeting vaccines in humans will depend on the composition of the human naive B cell repertoire, including the frequencies and affinities of epitope-specific B cells. However, the human naive B cell repertoire remains largely undefined. Assessment of antigen-specific human naive B cells among hundreds of millions of B cells from multiple donors may be used as pre–phase 1 ex vivo human testing to potentially forecast B cell and Ab responses to new vaccine designs. VRC01 is an HIV broadly neutralizing Ab (bnAb) against the envelope CD4-binding site (CD4bs). In this work, we characterized naive human B cells recognizing eOD-GT8, a germline-targeting HIV-1 vaccine candidate immunogen designed to prime VRC01-class Abs. Several distinct subclasses of VRC01-class naive B cells were identified, sharing sequence characteristics with inferred precursors of known bnAbs VRC01, VRC23, PCIN63, and N6. Multiple naive B cell clones exactly matched mature VRC01-class bnAb L-CDR3 sequences. Non–VRC01-class B cells were also characterized, revealing recurrent public light chain sequences. Unexpectedly, we also identified naive B cells related to the IOMA-class CD4bs bnAb. These different subclasses within the human repertoire had strong initial affinities (KD) to the immunogen, up to 13 nM, and represent encouraging indications that multiple independent pathways may exist for vaccine-elicited VRC01-class bnAb development in most individuals. The frequencies of these distinct eOD-GT8 B cell specificities give insights into antigen-specific compositional features of the human naive B cell repertoire and provide actionable information for vaccine design and advancement.

59 BASIC BIOLOGICAL SCIENCES↗