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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 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Pollen antigens and atmospheric circulation driven seasonal respiratory viral outbreak and its implication to the Covid-19 pandemic

Abstract The patterns of respiratory virus illness are expressed differently between temperate and tropical climates. Tropical outbreaks often peak in wet seasons. Temperate outbreaks typically peak during the winter. The prevailing causal hypotheses focus on sunlight, temperature and humidity variations. Yet no consistent factors have been identified to sufficiently explain seasonal virus emergence and decline at any latitude. Here we demonstrate close connections among global-scale atmospheric circulations, IgE antibody enhancement through seasonal pollen inhalation, and respiratory virus patterns at any populated latitude, with a focus on the US. Pollens emerge each Spring, and the renewed IgE titers in the population are argued to terminate each winter peak of respiratory illness. Globally circulated airborne viruses are postulated to subsequently deposit across the Southern US during lower zonal geostrophic winds each late Summer. This seasonally refreshed viral load is postulated to trigger a new influenza outbreak, once the existing IgE antibodies diminish to a critical value each Fall. Our study offers a new and consistent explanation for the seasonal diminishment of respiratory viral illnesses in temperate climates, the subdued seasonal signature in the tropics, the annually circulated virus phenotypes, and the northerly migration of influenza across the US every year. Our integrated geospatial and IgE hypothesis provides a new perspective for prediction, mitigation and prevention of the outbreak and spread of seasonal respiratory viruses including Covid-19 pandemic.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike mutations enable increased transmission and antibody resistance. We combined cryo–electron microscopy (cryo-EM), binding, and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans, and others that originated and spread in human populations. All variants showed increased angiotensin-converting enzyme 2 (ACE2) receptor binding and increased propensity for receptor binding domain (RBD)–up states. While adaptation to mink resulted in spike destabilization, the B.1.1.7 (UK) spike balanced stabilizing and destabilizing mutations. A local destabilizing effect of the RBD E484K mutation was implicated in resistance of the B.1.1.28/P.1 (Brazil) and B.1.351 (South Africa) variants to neutralizing antibodies. Our studies revealed allosteric effects of mutations and mechanistic differences that drive either interspecies transmission or escape from antibody neutralization.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Two human antibodies to a meningococcal serogroup B vaccine antigen enhance binding of complement Factor H by stabilizing the Factor H binding site

Microbial pathogens bind host complement regulatory proteins to evade the immune system. The bacterial pathogen Neisseria meningitidis, or meningococcus, binds several complement regulators, including human Factor H (FH). FH binding protein (FHbp) is a component of two licensed meningococcal vaccines and in mice FHbp elicits antibodies that inhibit binding of FH to FHbp, which defeat the bacterial evasion mechanism. However, humans vaccinated with FHbp develop antibodies that enhance binding of FH to the bacteria, which could limit the effectiveness of the vaccines. In the present study, we show that two vaccine-elicited antibody fragments (Fabs) isolated from different human subjects increase binding of complement FH to meningococcal FHbp by ELISA. The two Fabs have different effects on the kinetics of FH binding to immobilized FHbp as measured by surface plasmon resonance. The 1.7- and 2.0-Å resolution X-ray crystal structures of the Fabs in complexes with FHbp illustrate that the two Fabs bind to similar epitopes on the amino-terminal domain of FHbp, adjacent to the FH binding site. Superposition models of ternary complexes of each Fab with FHbp and FH show that there is likely minimal contact between the Fabs and FH. Collectively, the structures reveal that the Fabs enhance binding of FH to FHbp by altering the conformations and mobilities of two loops adjacent to the FH binding site of FHbp. In addition, the 1.5 Å-resolution structure of one of the isolated Fabs defines the structural rearrangements associated with binding to FHbp. The FH-enhancing human Fabs, which are mirrored in the human polyclonal antibody responses, have important implications for tuning the effectiveness of FHbp-based vaccines.

59 BASIC BIOLOGICAL SCIENCES↗