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DOE OSTI2023

Optimization of Spirulina for biomanufacturing and the delivery of protein therapeutics

Lumen Bioscience has developed a novel cyanobacterial platform that enormously decreases the cost of pharmaceuticals used to prevent and treat illnesses. Arthrospira platensis (spirulina), is a photosynthetic microorganism that has been consumed as a dietary supplement for centuries in part because of its high protein content. Commercial cultivation operations have matured over the last 50 years to allow large-scale cultivation in outdoor ponds. Lumen recently discovered methods that transform this commercially important cyanobacterium into a genetically tractable platform for bioengineering. The high protein accumulation in spirulina makes it an ideal chassis for heterologous protein expression, and centuries of safe human consumption suggest its utility as an administration vehicle for biologic drugs. Lumen can express a broad range of recombinant proteins in spirulina and has developed manufacturing processes and strains to mucosally deliver bioactive proteins to treat and/or prevent disease. For example, Lumen has produced an oral cocktail of dried whole-cell spirulina biomass, containing 3 toxin-neutralizing antibodies and 1 endolysin, that is efficacious in a preclinical in vivo models of C. difficile infection. Lumen has also demonstrated that intranasal administration of a spirulina-manufactured neutralizing antibody can prevent disease by a respiratory pathogen, SARS-CoV-2, in a hamster model. Lumen’s current pipeline includes therapeutics to treat or prevent C. difficile infection, COVID-19, inflammatory bowel disease, cardiometabolic disease, and traveler’s diarrhea. Lumen deploys strategies to maximize the expression of these therapeutics for optimal dose sizing, a key limiting factor with past food crop-based expression systems. Spirulina can express exogenous proteins at unusually high levels (>15% of dry weight) but reaching this maximum value requires optimization of multiple interacting factors. We describe our current statistics design of experiments approach that optimizes these factors with minimal replicates. This maximizes exogenous protein expression allowing Lumen to generate spirulina-based therapeutics for a rapidly expanding range of medical uses.

Heinnickel, Mark↗

DOE OSTI2021

PNNL DataHub Project: Omics Lethal Human Viruses Project Profiling of the Host Response to Influenza A Virus Infection, Processed Experimental Dataset Catalog

Influenza A virus (IAV) is a high risk biological agent, classified as a Category C priority pathogen (Orthomyxoviridae) by the National Institute of Allergy and Infectious Diseases (NIAID), and is known to cause severe respiratory disease with high mortality rates in humans. Lethal host-pathogen invasion mechanisms and the cellular intricacies behind these fatal infections still remain unclear. The NIAID Modeling Host Responses to Understand Severe Human Virus Infections Research Program project (2013-2018) aimed to develop an improved comprehensive understanding of the host response to a suite of viruses causing lethal infections leveraging a systems biology approach. Herein, PNNL sub-projects provide a never before released comprehensive infectious disease collection of primary and secondary transformation multi-Omics data profiling a series of priority pathogen primary experimental studies for enhanced open-access to viral Omics datasets and project lifecycle metadata. Secondary host-pathogen viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics (P), metabolomics (M), lipidomics (L), and transcriptomics (T) dataset downloads each have a direct relationship to a primary sample submission corresponding to a specific Influenza A virus [NCBITAXON:11320] experimental infection study. Host sample types include human lung adenocarcinoma cells ["Calu-3", BTO:0002750] and whole mouse lung [BTO:0000763] tissue collections.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

Omics Lethal Human Viruses Project Profiling of the Host Response to MERS-CoV Infection, Processed Experimental Dataset Catalog

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is classified as a Category C priority pathogen (Coronaviridae) by the National Institute of Allergy and Infectious Diseases (NIAID), and is known to cause severe respiratory disease with high mortality rates in humans. Lethal host-pathogen invasion mechanisms and the cellular intricacies behind these fatal infections still remain unclear. The NIAID Modeling Host Responses to Understand Severe Human Virus Infections Research Program project (2013-2018) aimed to develop an improved comprehensive understanding of the host response to a suite of viruses causing lethal infections leveraging a systems biology approach. Herein, PNNL sub-projects provide a never before released comprehensive infectious disease collection of primary and secondary transformation multi-Omics data profiling a series of priority pathogen primary experimental studies for enhanced open-access to viral Omics datasets and project lifecycle metadata. Secondary host-pathogen viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics (P), metabolomics (M), lipidomics (L), and transcriptomics (T) dataset downloads each have a direct relationship to a primary sample submission corresponding to a specific MERS-CoV [NCBITAXON:1335626] experimental infection study. Host sample types include human lung adenocarcinoma cells ["Calu-3", BTO:0002750], human bronchial epithelial cells ["Calu-3 clone 2B4"; BTO:0002022], primary human fibroblasts ["FB"; BTO:0000452], primary human airway epithelial cells ["HAE"; BTO:0005571], human microvascular endothelial cells ["HMVE"; BTO:0003123], and whole mouse lung [BTO:0000763] tissue collections.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2021

Towards Disentangling Lockdown-Driven Air Quality Changes in the Northeastern U.S.

In the absence of preventive therapies or effective treatment for most cases of coronavirus disease 2019 (COVID-19), governments worldwide have sought to minimize person-to-person severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission through a variety of lock-down measures and social distancing policies. Extreme events like the COVID-19 pandemic present a tremendous opportunity to make quantitative connections between changes in anthropogenic forcing, social and economic activity, and the related Earth system response. In this comment, we examine air quality impacts associated with pandemic response measures in the Northeastern United States.

Air Quality↗

NASA NTRS2014

Efficacy of Antimicrobials on Bacteria Cultured in a Spaceflight Analogue

As humans travel in space, they will interact with microbial flora from themselves, other crewmembers, their food, and the environment. While evaluations of microbial ecology aboard the Mir and ISS suggest a predominance of common environmental flora, the presence of (and potential for) infectious agents has been well documented. Likewise, pathogens have been detected during preflight monitoring of spaceflight food, resulting in the disqualification of that production lot from flight. These environmental and food organisms range from the obligate pathogen, Salmonella enterica serovar Typhimurium (S. Typhimurium), which has been responsible for disqualification and removal of food destined for ISS and has previously been reported from Shuttle crew refuse, to the opportunistic pathogen Staphylococcus aureus, isolated numerous times from ISS habitable compartments and the crew. Infectious disease events have affected spaceflight missions, including an upper respiratory infection that delayed the launch of STS-36 and an incapacitating Pseudomonas aeruginosa urinary tract infection of a crewmember during Apollo 13. These observations indicate that the crew has the potential to be exposed to obligate and opportunistic pathogens. This risk of exposure is expected to increase with longer mission durations and increased use of regenerative life support systems. As antibiotics are the primary countermeasure after infection, determining if their efficacy during spaceflight missions is comparable to terrestrial application is of critical importance. The NASA Rotating Wall Vessel (RWV) culture system has been successfully used as a spaceflight culture analogue to identify potential alterations in several key microbial characteristics, such as virulence and gene regulation, in response to spaceflight culture. We hypothesized that bacteria cultured in the low fluid shear RWV environment would demonstrate changes in efficacy of antibiotics compared to higher fluid shear controls. This study investigated the response of three medically significant microorganisms grown in the RWV to antibiotics that could be used on spaceflight missions. Our findings suggest potential alterations in antibiotic efficacy during spaceflight and indicate that future studies on the antibiotic response require additional basic research using the RWV and/or true spaceflight. However, while this analogue has reinforced these potential alterations, the results suggest the best approach for applied forward work is evaluating an in vivo system during spaceflight, including human and rodent studies. The complex nature of the analysis for many antibiotics and organism suggests the best approach to determine in vivo responses during pharmaceutical treatment is evaluating an in vivo system during spaceflight.

Nickerson, CA↗

NASA NTRS2007

Environmental Public Health Surveillance for Exposure to Respiratory Health Hazards: A Joint NASA/CDC Project to Use Remote Sensing Data for Estimating Airborne Particulate Matter Over the Atlanta, Georgia Metropolitan Area

As part of the National Environmental Public Health Tracking Network (EPHTN) the National Center for Environmental Health (NCEH) at the Centers for Disease Control and Prevention (CDC) is leading a project called Health and Environment Linked for Information Exchange (HELiX-Atlanta). The goal of developing the National Environmental Public Health Tracking Network is to improve the health of communities. Currently, few systems exist at the state or national level to concurrently track many of the exposures and health effects that might be associated with environmental hazards. An additional challenge is estimating exposure to environmental hazards such as particulate matter whose aerodynamic diameter is less than or equal to 2.5 micrometers (PM2.5). HELIX-Atlanta's goal is to examine the feasibility of building an integrated electronic health and environmental data network in five counties of Metropolitan Atlanta, GA. NASA Marshall Space Flight Center (NASA/MSFC) is collaborating with CDC to combine NASA earth science satellite observations related to air quality and environmental monitoring data to model surface estimates of PM2.5 concentrations that can be linked with clinic visits for asthma. While use of the Air Quality System (AQS) PM2.5 data alone could meet HELIX-Atlanta specifications, there are only five AQS sites in the Atlanta area, thus the spatial coverage is not ideal. We are using NASA Moderate Resolution Imaging Spectroradiometer (MODIS) satellite Aerosol Optical Depth (AOD) data for estimating daily ground level PM2.5 at 10 km resolution over the metropolitan Atlanta area supplementing the AQS ground observations and filling their spatial and temporal gaps.

Quattrochi, Dale A.↗

DOE OSTI2023

Elucidating regulatory processes of intense physical activity by multi-omics analysis

Abstract Background Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment. Methods To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student’s t -test followed by pathway analysis and comparison between the different omics modalities. Results Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection. Conclusion This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

Zinc against COVID-19? Symptom surveillance and deficiency risk groups

A wide variety of symptoms is associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and these symptoms can overlap with other conditions and diseases. Knowing the distribution of symptoms across diseases and individuals can support clinical actions on timelines shorter than those for drug and vaccine development. Here, we focus on zinc deficiency symptoms, symptom overlap with other conditions, as well as zinc effects on immune health and mechanistic zinc deficiency risk groups. There are well-studied beneficial effects of zinc on the immune system including a decreased susceptibility to and improved clinical outcomes for infectious pathogens including multiple viruses. Zinc is also an anti-inflammatory and anti-oxidative stress agent, relevant to some severe Coronavirus Disease 2019 (COVID-19) symptoms. Unfortunately, zinc deficiency is common worldwide and not exclusive to the developing world. Lifestyle choices and preexisting conditions alone can result in zinc deficiency, and we compile zinc risk groups based on a review of the literature. It is also important to distinguish chronic zinc deficiency from deficiency acquired upon viral infection and immune response and their different supplementation strategies. Zinc is being considered as prophylactic or adjunct therapy for COVID-19, with 12 clinical trials underway, highlighting the relevance of this trace element for global pandemics. Using the example of zinc, we show that there is a critical need for a deeper understanding of essential trace elements in human health, and the resulting deficiency symptoms and their overlap with other conditions. This knowledge will directly support human immune health for decreasing susceptibility, shortening illness duration, and preventing progression to severe cases in the current and future pandemics.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2010

Global Estimates of Average Ground-Level Fine Particulate Matter Concentrations from Satellite-Based Aerosol Optical Depth

Exposure to airborne particles can cause acute or chronic respiratory disease and can exacerbate heart disease, some cancers, and other conditions in susceptible populations. Ground stations that monitor fine particulate matter in the air (smaller than 2.5 microns, called PM2.5) are positioned primarily to observe severe pollution events in areas of high population density; coverage is very limited, even in developed countries, and is not well designed to capture long-term, lower-level exposure that is increasingly linked to chronic health effects. In many parts of the developing world, air quality observation is absent entirely. Instruments aboard NASA Earth Observing System satellites, such as the MODerate resolution Imaging Spectroradiometer (MODIS) and the Multi-angle Imaging SpectroRadiometer (MISR), monitor aerosols from space, providing once daily and about once-weekly coverage, respectively. However, these data are only rarely used for health applications, in part because the can retrieve the amount of aerosols only summed over the entire atmospheric column, rather than focusing just on the near-surface component, in the airspace humans actually breathe. In addition, air quality monitoring often includes detailed analysis of particle chemical composition, impossible from space. In this paper, near-surface aerosol concentrations are derived globally from the total-column aerosol amounts retrieved by MODIS and MISR. Here a computer aerosol simulation is used to determine how much of the satellite-retrieved total column aerosol amount is near the surface. The five-year average (2001-2006) global near-surface aerosol concentration shows that World Health Organization Air Quality standards are exceeded over parts of central and eastern Asia for nearly half the year.

Van Donkelaar, A.↗

NASA NTRS2010

Filovirus Research: The Need for an Integrated Approach in Time and Space

The episodic appearance of Ebola virus (EBOV) and Marburg virus (MARV) across central Africa over the last 15 years not only underscores the importance of filoviruses as uniquely virulent agents to both human and wildlife communities but also implies a very complex transmission scenario that must be understood if we are to prevent or mitigate filovirus outbreaks in the future. Efforts of a global network of scientists and healthcare workers have expanded our knowledge of filoviruses to meet the growing threat of Ebola and Marburg hemorrhagic fevers in Africa. In recent decades, several newly emerging diseases have resulted in major threats to both affected communities and global public health. Viruses from wildlife hosts in particular, have exhibited a capability for cross-species transmission (CST), and have caused high-impact diseases in humans Such as Ebola and Marburg hemorrhagic fevers, Nipah and severe acute respiratory syndrome (SAILS). It has been estimated that about 60.3% (Jones et al. 2008) of human infectious diseases are of animal origin (zoonoses) and even some important viral diseases that are traditionally considered of human origin, for example measles and smallpox, may very well have their prehistoric origins in wildlife (Wolfe et al 2007). It maybe logical and prudent therefore, to anticipate that there are other, new filoviruses out there that will cross into humans at some point in time. If we anticipate that these will happen and wish to be prepared for and mitigate this potential, then an understanding of filoviruses as a biologic system in the environment will be essential to that process. We will need to know how the ecological dynamic of CST interacts with a 'new' viruse's evolutionary factors to overcome environmental, demographic and host-specific barriers to transmission and infectivity to humans.

Pinzon, Jorge E.↗

NASA NTRS2011

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases as Medical Counter Measures

Exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. As biological damage from exposure is associated with increased oxidative stress, it would be enabling to mitigate and/or prevent stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological promoters for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for exposure. Furthermore, it also appears to have potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

Schoenfeld, Michael P.↗

NASA NTRS2008

Environmental Public Health Survelliance for Exposure to Respiratory Health Hazards: A Joint NASA/CDC Project to Use Remote Sensing Data for Estimating Airborne Particulate Matter Over the Atlanta, Georgia Metropolitan Area

Describes the public health surveillance efforts of NASA, in a joint effort with the Center for Disease Control (CDC). NASA/MSFC and the CDC are partners in linking nvironmental and health data to enhance public health surveillance. The use of NASA technology creates value - added geospatial products from existing environmental data sources to facilitate public health linkages. The venture sought to provide remote sensing data for the 5-country Metro-Atlanta area and to integrate this environmental data with public health data into a local network, in an effort to prevent and control environmentally related health effects. Remote sensing data used environmental data (Environmental Protection Agency [EPA] Air Quality System [AQS] ground measurements and MODIS Aerosol Optical Depth [AOD]) to estimate airborne particulate matter over Atlanta, and linked this data with health data related to asthma. The study proved the feasibility of linking environmental data (MODIS particular matter estimates and AQS) with health data (asthma). Algorithms were developed for QC, bias removal, merging MODIS and AQS particulate matter data, as well as for other applications. Additionally, a Business Associate Agreement was negotiated for a health care provider to enable sharing of Protected Health Information.

Quattrochi, Dale A.↗

NASA NTRS2011

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including, cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, parkinson s and alzheimer s disease, cataracts, and aging

Schoenfeld, Michael P.↗

NASA NTRS2012

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases as Medical Counter Measures

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

Schoenfeld, Michael P.↗

NASA NTRS2011

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

Schoenfeld, Michael P.↗

DOE OSTI2020

Multi-omics Characterization of the Host Response to COVID-19

This project is a multi-disciplinary collaboration between investigators at PNNL with expertise in mass spectrometry (MS)-based omics technology development, omics measurement methods development and application, statistics, machine learning and integration of disparate datasets for a systems-level understanding, and expertise in pathogenic coronaviruses, and investigators at the University of Wisconsin-Madison (UW-Madison) with expertise in pathogenic respiratory viruses (e.g. influenza). The goal of this project is to obtain a comprehensive picture of the human host factors critical for the outcome of SARS-CoV-2 infection. We will generate broad untargeted multi-omics profiles using both state-of-the-art and novel instrumentation and approaches to enable the identification of the molecular mechanisms and host response pathways that impact human COVID-19 outcomes. We anticipate these results will lead to the generation of biomarker panels that are predictive of disease outcomes and mechanistic hypotheses that can be further interrogated in future studies and will provide the basis for vaccine or therapeutic development. To do so, we are obtaining and analyzing blood samples from COVID-19 patients with a range of disease outcomes that were treated at the Center Hospital of the National Center for Global Health and Medicine in Tokyo, Japan and other collaborating hospitals in our network. Specifically, this project will fund proteomics and metabolomics analyses of clinical COVID samples, machine learning-based integration of the data, and pathway-based interpretation of the data. This project was funded in June 2020. In the time span of June to September 2020, the project team developed an analytically and statistically robust analysis plan and made various preparations to facilitate sample receipt from our UW-Madison collaborators. This included blocking and randomization of sample prep orders, ordering of reagents and reference materials, and shipping of materials needed for preparation of the samples under BSL3 conditions to our collaborators at UW-Madison. As of FY21, this project has been picked up via a sponsor, the Naval Medical Research Center, which will cover the remainder of the proposed scope of work.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2023

Single-dose mucosal replicon-particle vaccine protects against lethal Nipah virus infection up to 3 days after vaccination

Nipah virus (NiV) causes a highly lethal disease in humans who present with acute respiratory or neurological signs. No vaccines against NiV have been approved to date. Here, we report on the clinical impact of a novel NiV-derived nonspreading replicon particle lacking the fusion (F) protein gene (NiVΔF) as a vaccine in three small animal models of disease. A broad antibody response was detected that included immunoglobulin G (IgG) and IgA subtypes with demonstrable Fc-mediated effector function targeting multiple viral antigens. Single-dose intranasal vaccination up to 3 days before challenge prevented clinical signs and reduced virus levels in hamsters and immunocompromised mice; decreases were seen in tissues and mucosal secretions, critically decreasing potential for virus transmission. This virus replicon particle system provides a vital tool to the field and demonstrates utility as a highly efficacious and safe vaccine candidate that can be administered parenterally or mucosally to protect against lethal Nipah disease.

60 APPLIED LIFE SCIENCES↗

NASA NTRS2005

Environmental Public Health Tracking: Health and Environment Linked for Information Exchange-Atlanta (HEXIX-Atlanta: A cooperative Program Between CDC and NASA for Development of an Environmental Public Health Tracking Network in the Atlanta Metropolitan Area

The Centers for Disease Control and Prevention (CDC) is coordinating HELIX- Atlanta to provide information regarding the five-county Metropolitan Atlanta Area (Clayton, Cobb, DeKalb, Fulton, and Gwinett) via a network of integrated environmental monitoring and public health data systems so that all sectors can take action to prevent and control environmentally related health effects. The HELIX-Atlanta Network is a tool to access interoperable information systems with optional information technology linkage functionality driven by scientific rationale. HELIX-Atlanta is a collaborative effort with local, state, federal, and academic partners, including the NASA Marshall Space Flight Center. The HELIX-Atlanta Partners identified the following HELIX-Atlanta initial focus areas: childhood lead poisoning, short-latency cancers, developmental disabilities, birth defects, vital records, respiratory health, age of housing, remote sensing data, and environmental monitoring, HELIX-Atlanta Partners identified and evaluated information systems containing information on the above focus areas. The information system evaluations resulted in recommendations for what resources would be needed to interoperate selected information systems in compliance with the CDC Public Health Information Network (PHIN). This presentation will discuss the collaborative process of building a network that links health and environment data for information exchange, including NASA remote sensing data, for use in HELIX-Atlanta.

Quattrochi, Dale A.↗