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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 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Systematic Screening of COVID-19 Disease Based on Chest CT and RT-PCR for Cancer Patients Undergoing Radiation Therapy in a Coronavirus French Hotspot

Patients with cancer are presumed to be more vulnerable to COVID-19. We evaluated a screening strategy combining chest computed tomography (CT) and reverse-transcription polymerase chain reaction (RT-PCR) for patients treated with radiation therapy at our cancer center located in a COVID-19 French hotspot during the first wave of the pandemic.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Engineered immunogens to elicit antibodies against conserved coronavirus epitopes

Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Persistence of viral RNA in North American elk experimentally infected with an ancestral strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Abstract White-tailed deer (Odocoileus virginianus) have emerged as a reservoir host for SARS-CoV-2 given their susceptibility to infection and demonstrated high rates of seroprevalence and infection across the United States. As SARS-CoV-2 circulates within free-ranging white-tailed deer populations, there is the risk of transmission to other wildlife species and even back to the human population. The goal of this study was to determine the susceptibility, shedding, and immune response of North American elk (Cervus elaphus canadensis) to experimental infection with SARS-CoV-2, to determine if another wide-ranging cervid species could potentially serve as a reservoir host for the virus. Here we demonstrate that while North American elk do not develop clinical signs of disease, they do develop a neutralizing antibody response to infection, suggesting the virus is capable of replicating in this mammalian host. Additionally, we demonstrate SARS-CoV-2 RNA presence in the medial retropharyngeal lymph nodes of infected elk three weeks after experimental infection. Consistent with previous observations in humans, these data may highlight a mechanism of viral persistence for SARS-CoV-2 in elk.

Science & Technology - Other Topics↗
DOE OSTI2023

Building a Computational and Experimental Rapid Response Pipeline to Counter the Coronavirus Disease 2019 Outbreak and Emerging Biothreats

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs, especially where protective candidates can be rapidly identified or developed for emerging biothreats and escape variants. Current cutting-edge technologies for this purpose still rely on pathogen-exposed convalescent volunteers and a large screening effort to find a proverbial needle in a haystack. Computational design of protective antibodies based on pre-existing templates skips those requirements and allows for greater control over the breadth and target epitope, while also co-optimizing for potency and developability or other biophysical characteristics. We approached this problem by building and expanding an in vitro experimental rapid antibody production and characterization pipeline to support development of an autonomous, closed loop, active learning software system based on structural simulation and ground truth experimental data to design and evaluate antibody antigen interactions. Starting from early in the pandemic, we targeted SARS-CoV-2, the causative agent of COVID-19, by re-purposing neutralizing antibodies against SARS-CoV-1 that had been identified in the wake of that outbreak in the early 2000’s. We successfully re-targeted three different anti-SARS-CoV-1 antibodies to neutralize SARS-CoV-2 in vitro, where the antibodies were generated externally and tested through conventional binding and neutralization assays internally or with collaborators. As antibodies were identified from the blood of humans infected with SARS-CoV-2, we shifted to collaborate with academic partners to develop improved versions of their human-derived antibodies. This work reached its most important stage in rapid response to the emergence of the Omicron variant of concern (VOC) in late 2021. In a matter of weeks, enabled by on demand innovation to our screening pipeline, we computationally designed and experimentally characterized derivative antibodies of COV2-2130, one of two antibodies from Vanderbilt that form the basis of the AstraZeneca Evusheld prophylactic drug product. This drug product suffers a serious loss of efficacy against Omicron BA.1 and BA.1.1, the first Omicron strains. Due to tight integration of computational design and experimental evaluation, we were able to identify a pair of designs with potent neutralization of the main targets Omicron BA.1 and BA.1.1; but also the earlier Delta variant, and subsequent Omicron strains including BA.2, BA.4, BA.5, and BA.2.75, demonstrating that our multi-target design process can, by its nature, produce robust antibody designs that strictly improve over the parental antibody. These results, recognized by a 2022 Director’s Science and Technology award, have enabled the follow-on GUIDE program, to commence in FY23. While earlier design campaigns were substantially outsourced, we have engineered better and faster processes internally to better compliment, calibrate, and speed computational designs. As part of the follow-on GUIDE program, we will stand up a rapid and high-throughput antibody production and characterization facility staffed with the expertise and capabilities to foster our current collaboration across PLS and ENG as well as other partnerships toward computational design of biologics.

59 BASIC BIOLOGICAL SCIENCES↗