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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 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2012

Alterations of Cellular Immune Reactions in Crew Members Overwintering in the Antarctic Research Station Concordia

Background: Concordia Station is located inside Antarctica about 1000km from the coast at an altitude of 3200m (Dome C). Hence, individuals living in this harsh environment are exposed to two major conditions: 1.) hypobaric hypoxia and 2.) confinement and extreme isolation. Both hypoxia and confinement can affect human immunity and health, and are likely to be present during exploration class space missions. This study focused on immune alterations measured by a new global immunity test assay, similar to the phased out delayed type hypersensitivity (DTH) skin test. Methods: After informed written consent 14 healthy male subjects were included to the CHOICE-study (Consequences-of-longterm-Confinement-and-Hypobaric-HypOxia-on-Immunity-in-the Antarctic-Concordia-Environment). Data collection occurred during two winter-over periods lasting each one year. During the first campaign 6 healthy male were enrolled followed by a second campaign with 8 healthy males. Blood was drawn monthly and incubated for 48h with various bacterial, viral and fungal antigens followed by an analysis of plasma cytokine levels (TNF-alpha, IL2, IFN-gamma, IL10). As a control, blood was incubated without stimulation ("resting condition"). Goals: The scope of this study was to assess the consequences of hypoxia and confinement on cellular immunity as assessed by a new in vitro DTH-like test. Results: Initial results indicate that under resting conditions the in vitro DTH-like test showed low cytokine levels which remained almost unchanged during the entire observation period. However, cytokine responses to viral, bacterial and fungal antigens were remarkably reduced at the first month after arrival at Concordia when compared to levels measured in Europe prior to departure for Antarctica. With incrementing months of confinement this depressed DTH-like response tended to reverse, and in fact to show an "overshooting" immune reaction after stimulation. Conclusion: The reduced in vitro DTH-like test response in the early phase of Antarctic wintering over con rms distinct immune suppressive effects seen after (sub-)acute hypobaric hypoxia. The reversal and overshooting reaction of cellular immune responses upon stimulation, but not the resting state, indicate either a) priming of immune answers and/or b) an uncoupled or disregulated control of cellular immune answers by auto-, para- and endocrine pathways. Further analyses and correlations are warranted. Acknowledgement: Supported by the European Space Agency (ESA), the French (IPEV) and Italian (PNRA) polar institutes, the German National Space Program (DLR, 50WB0719/WB0919), by BELSPO/PROEDEX/ESA (C90-380/-391), NASA and by the Concordia crews who have participated with great enthusiasm.

Crucian, Brian↗
NASA NTRS2010

Particular Characterisation of an In-Vitro-DTH Test to Monitor Cellular Immunity - Applications for Patient Care and Space Flight

Goal:i) Characterization of the role of the main immune reactive cell types contributing to the cellular immune response in the in-vitro DTH and ii) Validation of the in-vitro DTH under different clinical and field conditions. Methods:As positive control whole blood was incubated in the in-vitro DTH, supernatants were gathered after 12, 24 and 48h. Readout parameters of this test are cytokines in the assay's supernatant. To determine the role of T-cells, monocytes and natural killer (NK), these cell populations were depleted using magnetic beads prior to in-vitro-DTH incubation. Validation of the test has occurred under clinical (HIV-patients, ICU) and field-conditions (parabolic/space-flights, confinement). Results:T-cell depletion abandoned almost any IL-2 production and reduced IFN-gamma production irrespective of the type of antigen, whereas CD56 depleted cultures tended to lower IL-2 secretion and IFN-gamma and to parallel a IL-10-increase after viral challenge. This IL-10-increase was seen also in CD14-depleted setups. DTH read-out was significantly different under acute stress (parabolic flight) or chronic stress (ISS), respectively. Preliminary data of HIV infected patients demonstrate that this test can display the contemporary immune status during an antiviral therapy. Conclusion:The in-vitro DTH mirrors adaptive and innate immune activation and may serve as tool also for longitudinal follow up of Th1/Th2 weighed immune response under adverse life conditions on earth and in space. It is planned to implement the assay in the on the ISS (MoCISS).

Feurecker, M.↗
NASA NTRS1991

Cellular immunity and lymphokine production during spaceflights

Results are presented on changes in cellular immunity and in the production of lymphokine in spacecrews during spaceflights. Measurements were carried out on blood samples collected from 50 cosmonauts before and after spaceflights of different duration, on board Salyut-6, Salyut-7, or Mir. Additional data were obtained from rats flown on board the Cosmos-1667 and Cosmos-1887 biosatellites. The parameters measured included the PHA responsiveness of T lymphocytes, the activity of T-helper cells and of nonspecific T suppressors, the activity of the so-called natural killer lymphocytes, the production of gamma-interferon, and the cell-surface markers. Results showed that the frequency and the extent of changes in the immunologic resistance of subjects depended on the duration of the flight. However, even after the most prolonged (365 days) spaceflight, the changes observed were mostly of a functional character with subsequent rapid return to normal.

Konstantinova, I. V.↗
NASA NTRS1974

Early detection of disease program: Evaluation of the cellular immune response

The early cellular responses of specific components of the leukocyte and epithelial cell populations to foreign challenges of both an infectious and noninfectious character were evaluated. Procedures for screening potential flight crews were developed, documented, and tested on a control population. Methods for preparing suitable populations of lymphocytes, polymorphonuclear leukocytes, macrophages, and epithelial cells were first established and evaluated. Epithelial cells from viral infected individuals were screened with a number of anti-viral antisera. This procedure showed the earliest indication of disease as well as providing a specific diagnosis to the physicians. Both macrophages and polymorphonuclear leukocytes were studied from normal individuals, smokers, and patients with viral infections. Newer techniques enabling better definition of lymphocyte subpopulations were then developed, namely the E and EAC rosette procedures for recognition of T (thymus-derived) and B (bone-marrow-derived) lymphocyte subpopulations. Lymphocyte and lymphocyte subpopulation response to multiple mitogens have been evaluated.

Criswell, B. S.↗
NASA NTRS1976

Cellular immune response experiment MA-031

Significant changes in phytohemagglutinin (PHA) lymphocytic responsiveness occurred in the cellular immune response of three astronauts during the 9 day flight of the Apollo Soyuz Test Project. Parameters studied were white blood cell concentrations, lymphocyte numbers, B- and T-lymphocyte distributions in peripheral blood, and lymphocyte responsiveness to PHA, pokeweed mitogen, Concanavalin A, and influenza virus antigen.

Criswell, B. S.↗
NASA NTRS2002

Dietary nucleotides prevent decrease in cellular immunity in ground-based microgravity analog

Microgravity and stress of spaceflights result in immune dysfunction. The role of nutrition, especially nucleotide supplementation, has become an area of intensive research and significant interest in immunomodulation for maintenance of cellular immune responses. The studies presented here evaluate the plausibility of administering nucleotides to obviate immune dysfunction in an Earth-based in vivo analog of microgravity as studied in anti-orthostatic tail suspension (AOS) of mice. Mice were divided into three housing groups: group, isolation, and AOS. Mice were fed either control chow diet (CD), or RNA-, adenine-, or uracil-supplemented CD for the 1-wk duration of the experiments. In AOS mice, supplemental nucleotides significantly increased in vivo lymph node proliferation and ex vivo lymphoproliferation response to alloantigen and mitogens, respectively, and interleukin-2 and interferon-gamma production. A lower corticosterone level was observed in uracil-supplemented CD compared with CD. These results suggest that exogenous nucleotide supplementation, especially uracil, of normal diet is beneficial in the maintenance and restoration of the immune response during the microgravity analog conditions.

NASA Center JSC↗
DOE OSTI2021

Polymersomes Decorated with the SARS-CoV-2 Spike Protein Receptor-Binding Domain Elicit Robust Humoral and Cellular Immunity

The COVID-19 pandemic underscores the need for rapid, safe, and effective vaccines. In contrast to some traditional vaccines, nanoparticle-based subunit vaccines are particularly efficient in trafficking antigens to lymph nodes, where they induce potent immune cell activation. Here, we developed a strategy to decorate the surface of oxidation-sensitive polymersomes with multiple copies of the SARS-CoV-2 spike protein receptor-binding domain (RBD) to mimic the physical form of a virus particle. We evaluated the vaccination efficacy of these surface-decorated polymersomes (RBD surf ) in mice compared to RBD-encapsulated polymersomes (RBD encap ) and unformulated RBD (RBD free ), using monophosphoryl-lipid-A-encapsulated polymersomes (MPLA PS) as an adjuvant. While all three groups produced high titers of RBD-specific IgG, only RBD surf elicited a neutralizing antibody response to SARS-CoV-2 comparable to that of human convalescent plasma. Moreover, RBD surf was the only group to significantly increase the proportion of RBD-specific germinal center B cells in the vaccination-site draining lymph nodes. Both RBD surf and RBD encap drove similarly robust CD4 + and CD8 + T cell responses that produced multiple Th1-type cytokines. We conclude that a multivalent surface display of spike RBD on polymersomes promotes a potent neutralizing antibody response to SARS-CoV-2, while both antigen formulations promote robust T cell immunity.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults

Mosaic and consensus HIV-1 immunogens provide two distinct approaches to elicit greater breadth of coverage against globally circulating HIV-1 and have shown improved immunologic breadth in nonhuman primate models. This double-blind randomized trial enrolled 105 healthy HIV-uninfected adults who received 3 doses of either a trivalent global mosaic, a group M consensus (CON-S), or a natural clade B (Nat-B) gp160 env DNA vaccine followed by 2 doses of a heterologous modified vaccinia Ankara–vectored HIV-1 vaccine or placebo. We performed prespecified blinded immunogenicity analyses at day 70 and day 238 after the first immunization. T cell responses to vaccine antigens and 5 heterologous Env variants were fully mapped. Env-specific CD4 + T cell responses were induced in 71% of the mosaic vaccine recipients versus 48% of the CON-S recipients and 48% of the natural Env recipients. The mean number of T cell epitopes recognized was 2.5 (95% CI, 1.2–4.2) for mosaic recipients, 1.6 (95% CI, 0.82–2.6) for CON-S recipients, and 1.1 (95% CI, 0.62–1.71) for Nat-B recipients. Mean breadth was significantly greater in the mosaic group than in the Nat-B group using overall (P = 0.014), prime-matched (P = 0.002), heterologous (P = 0.046), and boost-matched (P = 0.009) measures. Overall T cell breadth was largely due to Env-specific CD4 + T cell responses. Priming with a mosaic antigen significantly increased the number of epitopes recognized by Env-specific T cells and enabled more, albeit still limited, cross-recognition of heterologous variants. Mosaic and consensus immunogens are promising approaches to address global diversity of HIV-1.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1975

Early detection of disease program: Evaluation of the cellular immune response

Surfaces of normal, cultured, and mitogen-stimulated mouse lymphoid cells were examined by scanning electron microscopy (SEM). Lymphocytes with smooth, highly villous and intermediate surfaces were observed in cell suspensions from both spleens and thymuses of normal mice and from spleens of congenitally athymic (nude) mice. Several strain-specific surface features were noted, including the spine-like appearance of microvilli on C57B1/6 lymphocytes. Although thymus cell suspensions contained somewhat more smooth cells than did spleen cell preparations, lymphocyte derivation could not be inferred from SEM examination. Studies of cells stimulated with mitogenic agents for thymus-derived lymphocytes (concanavalin A) or for bone marrow-derived lymphocytes (lipopolysaccharide) suggested that, in the mouse, development of a complex villous surface is a general concomitant of lymphocyte activation and transformation.

Criswell, B. S.↗
NASA NTRS1983

Human cellular immune responsiveness following space flight

Peripheral circulating lymphocytes were separated from astronaut blood samples three times before and two times after the first four US Space Shuttle flights. The ability of the in vitro T lymphocytes to respond to Phytohemagglutinin by blastogenesis was found to be reduced for each crewmember following spaceflight. In addition, the astronauts experienced a postflight increase in neutrophils and a decrease in eosinophils. These postflight changes in leukocytes are shown to increase with subjectively-evaluated increases in the incidence of inflight stress, indicating that stress, and not hypogravity, is likely to be the major effector of these changes.

Taylor, G. R.↗
NASA NTRS2000

Cell-Mediated Immune Function and Cytokine Regulation During Space Flight

The changes in immune function which occur during space flight potentially expose the crews to an increased risk for development of illness. Decreased cellular immune function has been repeatedly documented after space flight and confirmed during flight by in vivo delayed-type hypersensitivity testing. However, correlation of immune changes with a clinically significant risk factor has not yet been performed. Our hypothesis is that space flight induces a decrease in cell-mediated immune function accompanied by a shift from a type 1 cytokine pattern (favoring cell-mediated immunity) to a type 2 cytokine pattern (favoring humoral immunity). We further hypothesize that reactivation of latent viruses will occur during space flight in association with the decreased cellular immunity. To test these hypotheses, we will determine the effects of space flight on cell-mediated immunity and viral reactivation. We will utilize delayed-type hypersensitivity testing as an in vivo measure of integrated cell-mediated immune function. The production of cytokines and immunoregulatory factors by lymphocytes and monocytes will be measured to determine whether changes in cytokine patterns are associated with the space flight-induced immune dysregulation. Correlation of antigen-specific immune changes with reactivation of latent herpes viruses will be determined by measuring peripheral levels of viral (CMV, VZV, EBV) antigen-specific T cells and comparing to the levels of EBV-infected B-cells by fluorescence in situ hybridization and flow cytometry. A comparison of cell-mediated immune function, cytokine regulation and viral reactivation will provide new insights into crew member health risks during flight.

Sams, Clarence F.↗
DOE OSTI2024

Evaluation of two inoculation routes of an adenovirus-mediated viral protein inhibitor in a Crimean-Congo hemorrhagic fever mouse model

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne nairovirus with a wide geographic spread that can cause severe and lethal disease. No specific medical countermeasures are approved to combat this illness. The CCHFV L protein contains an ovarian tumor (OTU) domain with a cysteine protease thought to modulate cellular immune responses by removing ubiquitin and ISG15 post-translational modifications from host and viral proteins. Viral deubiquitinases like CCHFV OTU are attractive drug targets, as blocking their activity may enhance cellular immune responses to infection, and potentially inhibit viral replication itself. We previously demonstrated that the engineered ubiquitin variant CC4 is a potent inhibitor of CCHFV replication in vitro. A major challenge of the therapeutic use of small protein inhibitors such as CC4 is their requirement for intracellular delivery, e.g., by viral vectors. In this study, we examined the feasibility of in vivo CC4 delivery by a replication-deficient recombinant adenovirus (Ad-CC4) in a lethal CCHFV mouse model. Since the liver is a primary target of CCHFV infection, we aimed to optimize delivery to this organ by comparing intravenous (tail vein) and intraperitoneal injection of Ad-CC4. While tail vein injection is a traditional route for adenovirus delivery, in our hands intraperitoneal injection resulted in higher and more widespread levels of adenovirus genome in tissues, including, as intended, the liver. However, despite promising in vitro results, neither route of in vivo CC4 treatment resulted in protection from a lethal CCHFV infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Longitudinal proteomics analysis in the immediate microenvironment of islet allografts during progression of rejection

The applicability and benefits of pancreatic islet transplantation are limited due to various issues including the need to avoid immune-mediated rejection. In the present study, we used our experimental platform of allogeneic islet transplant in the anterior chamber of the eye (ACE-platform) to longitudinally monitor the progress of rejection in mice and obtain aqueous humor samples representative of the microenvironment of the graft for accurately-timed proteomic analyses. LC-MS/MS-based proteomics performed on such mass-limited samples (~5 μL) identified a total of 1296 proteins. Various analyses revealed distinct protein patterns associated with the mounting of the inflammatory and immune responses and their evolution with the progression of the rejection. Pathway analyses indicated predominant changes in cytotoxic functions, cell movement, and innate and adaptive immune responses. Furthermore, network prediction analyses revealed transition from humoral to cellular immune response and exacerbation of pro-inflammatory signaling. One of the proteins identified by this localized proteomics as a candidate biomarker of islet rejection, Cystatin 3, was further validated by ELISA in the aqueous humor. This study provides (1) experimental evidence demonstrating the feasibility of longitudinal localized proteomics using small aqueous humor samples and (2) proof-of-concept for the discovery of biomarkers of impending immune attack from the immediate local microenvironment of ACE-transplanted islets.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Antigenic combinations against Francisella bacteria and related nanolipoprotein particles, compositions, methods and systems

Provided herein are antigenic combinations and related compositions, methods and systems for immunizing a host from an infection caused by Francisella bacterium. The antigenic combination comprises an antigenic polysaccharide component from a Francisella bacterium capable of triggering a humoral immune response in an individual, a protein antigen component from the Francisella bacterium capable of triggering a cellular immune response in the individual, and an adjuvant, the antigenic Francisella polysaccharide component, the Francisella protein antigen component and the adjuvant are in a suitable amount to immunize an individual against the Francisella bacterium.

Fischer, Nicholas↗
NASA NTRS1993

Immune changes in humans concomitant with space flights of up to 10 days duration

The time relation of various classes of in-flight human physiological changes is illustrated. Certain problems, such as neurovestibular, fluid, and electrolyte imbalances tend to occur early in a flight, followed by stabilization at some microgravity equilibrium level. Cardiovascular dysfunctions and erythrocyte mass losses appear to follow a similar pattern, although the significant changes occur later in flight. Bone and calcium changes and radiation effects are thought to progressively worsen with time, whereas the time course of immune change is yet to be fully understood. Significant immunologic changes in cosmonauts and astronauts during and after space flight have been documented as have microbiological changes. Thus, space flight can be expected to effect a blunting of the human cellular immune mechanism concomitant with a relative increase in potentially pathogenic microorganisms. This combination would seem to increase the probability of infectious disease events in flight.

Taylor, Gerald R.↗
DOE OSTI2024

Crimean Congo hemorrhagic fever virus nucleoprotein and GP38 subunit vaccine combination prevents morbidity in mice

Immunizing mice with Crimean-Congo hemorrhagic fever virus (CCHFV) nucleoprotein (NP), glycoprotein precursor (GPC), or with the GP38 domain of GPC, can be protective when the proteins are delivered with viral vectors or as a DNA or RNA vaccine. Subunit vaccines are a safe and cost-effective alternative to some vaccine platforms, but Gc and Gn glycoprotein subunit vaccines for CCHFV fail to protect despite eliciting high levels of neutralizing antibodies. Here, we investigated humoral and cellular immune responses and the protective efficacy of recombinant NP, GP38, and GP38 forms (GP85 and GP160) associated with the highly glycosylated mucin-like (MLD) domain, as well as the NP + GP38 combination. Vaccination with GP160, GP85, or GP38 did not confer protection, and vaccination with the MLD-associated GP38 forms blunted the humoral immune responses to GP38, worsened clinical chemistry, and increased viral RNA in the blood compared to the GP38 vaccination. In contrast, NP vaccination conferred 100% protection from lethal outcome and was associated with mild clinical disease, while the NP + GP38 combination conferred even more robust protection by reducing morbidity compared to mice receiving NP alone. Thus, recombinant CCHFV NP alone is a promising vaccine candidate conferring 100% survival against heterologous challenge. Moreover, incorporation of GP38 should be considered as it further enhances subunit vaccine efficacy by reducing morbidity in surviving animals.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Impact of Selenium and Vitamin E Deficiency on Zika Virus Pathogenesis and Immune Response in Mice

Micronutrient status is recognized to influence host susceptibility to viral infections, yet its impact on Zika virus (ZIKV) pathogenesis remains incompletely understood. We investigated the effects of dietary selenium and combined selenium plus vitamin E deficiency on ZIKV infection outcomes in a type I interferon α/β receptor knockout (Ifnar1 −/− ) murine model. Mice maintained on deficient diets exhibited significantly lower neutralizing antibody titers and reduced levels of key antiviral cytokines (IFN-γ, TNF-α, IFN-α, IFN-β, IL-12p70, CCL5) compared to controls. Correspondingly, higher viral RNA loads were detected in the brains of double-deficient mice, which also experienced greater weight loss and increased mortality. Deep sequencing revealed no major differences in overall viral genome diversity across diet groups; however, specific mutations, including V330L and D67E in the E gene, and V360I in the NS3 gene, were enriched or detected in nutritionally deficient animals. These findings suggest that antioxidant micronutrient deficiency impairs both humoral and cellular immune responses to ZIKV, potentially facilitating enhanced neuroinvasion. While the functional consequences of the identified mutations warrant further investigation, our results underscore the importance of adequate micronutrient intake for optimal antiviral defense. Further studies are needed to clarify the epidemiological significance of these observations.

Biological and medical sciences↗
DOE OSTI2026

Circadian immunometabolic states impart a temporal response to SARS-CoV-2 spike proteins in mammalian macrophages

Circadian rhythms, the 24-hour cycles that tune organismal physiology to the daily rhythms of light and dark, optimally organize cellular processes such as metabolism and mitochondrial function. In mammals, macrophage functions are regulated by these 24-hour circadian rhythms such that the immunometabolic response is coordinated across the day, consolidating macrophage physiology into temporally distinct phases to time the cellular immune response. However, while it is known that there are time-of-day specific responses to stress in a macrophage, little has been done to determine if circadian regulation coordinates the response of a macrophage to real-world pathogens. Importantly, key proteins in the response to viral infection have been found to be under circadian control, and time of day of application is known to affect the efficacy of vaccinations, including in the case of the COVID-19 virus. Therefore, to investigate if the circadian regulation of macrophage physiology imparted a time-of-day response to viral exposure, we exposed primary mouse and human macrophages to the SARS-CoV-1 and CoV-2 spike proteins at different times over the circadian day. To establish a time-of-day effect, we performed a multi-omics analysis and in vitro tissue culture assays examining macrophage responses over circadian time. We found that, conserved across the species, the timing of spike protein exposure dictated two distinct temporal responses which were characterized by hallmarks of immunometabolic suppression and modest inflammatory activation. However, these responses were primarily influenced by central metabolic and mitochondrial changes and not by classical immune activation.

Circadian Biology↗