The Effects of Long-Term Exposure to Microgravity on Salivary Markers of Innate Immunity (Salivary Markers) - 07.29.14

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The Effects of Long-Term Exposure to Microgravity on Salivary Markers of Innate Immunity (Salivary Markers) investigation involves the collection of blood, saliva, urine and a health assessment on six subjects pre-, in- and post-flight to determine if spaceflight induced immune system dysregulation increases infection susceptibility or poses a significant health risk to crewmembers onboard the International Space Station. The investigation utilizes a longitudinal, repeated measures design to determine the effects of long-term exposure to microgravity on a host of salivary antimicrobial proteins (AMPs), latent viral reactivation, antibacterial properties of saliva, and blood markers associated with innate host immune defense.
 

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This content was provided by Richard J. Simpson, Ph.D., and is maintained in a database by the ISS Program Science Office.

Experiment Details

OpNom Salivary Markers

Principal Investigator(s)

  • Richard J. Simpson, Ph.D., Department of Health and Human Performance, Houston, TX, United States

  • Co-Investigator(s)/Collaborator(s)
  • Brian E. Crucian, Ph.D., Wyle Laboratories, Houston, TX, United States
  • Thomas W. Lowder, Ph.D., Department of Health and Human Performance, University of Houston, Houston, TX, United States
  • Mark S. Clarke, Ph.D., University of Houston/JSC Space Center, Houston, TX, United States
  • Guillaume Spielmann, Ph.D., University of Houston, Houston, TX, United States
  • Daniel O' Connor, PhD., Houston, TX, United States
  • Duane L. Pierson, Ph.D., Johnson Space Center, Houston, TX, United States
  • Satish K. Mehta, Ph.D., Enterprise Advisory Services Incorporated, Houston, TX, United States

  • Developer(s)
    Johnson Space Center, Human Research Program, Houston, TX, United States

    Sponsoring Space Agency
    National Aeronautics and Space Administration (NASA)

    Sponsoring Organization
    Human Exploration and Operations Mission Directorate (HEOMD)

    Research Benefits
    Earth Benefits, Scientific Discovery, Space Exploration

    ISS Expedition Duration
    March 2013 - Ongoing

    Expeditions Assigned
    35/36,37/38,39/40,41/42,43/44,45/46

    Previous ISS Missions

    Integrated Immune


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    Experiment Description

    Research Overview

    • Future space exploration missions are dependent on a robust immune system to minimize the risk of infection among crewmembers. It is not known if the immune system is impaired during long-duration (i.e., several months vs. weeks) spaceflight because previous research in this area has been restricted to short-duration spaceflight missions. Also, because the effects of spaceflight on immunity have been assessed using blood and saliva samples collected from crewmembers immediately after returning to Earth, it is not known if these observed changes in immune function are due to prolonged periods in space or whether they are due to the stressors associated with landing. It is therefore important to collect blood, urine and saliva samples during spaceflight (i.e., on the International Space Station) so that the true effects of spaceflight on the human immune system can be determined. This research study will be important to determine if any risks to crewmembers exist as a result of impaired immunity.
    • Blood, urine and saliva samples will be collected before, during and after long-duration missions to the ISS. These samples will be used to measure markers of latent viral reactivation (a global indicator of immune impairment and infection risk) in conjunction with salivary antimicrobial proteins and immune cell functional assays. As we will collect our samples during flight and return these to Earth for analysis, we will be able to determine if any changes in immune function occur during flight that could leave the crewmember at an increased risk of infection and illness.
    • This research study will help identify if there are any risks of an adverse health event in crewmembers due to an impaired immune system. Maintaining a robust immune system during prolonged spaceflight missions (i.e., to other planets or asteroids) will be important to ensure mission success. If any impairments in immunity are found due to spaceflight, this will allow us to develop appropriate countermeasures to help mitigate the risks.
       

     

    Description

    The goal of the Salivary Markers study is to determine if spaceflight induced immune system dysregulation increases infection susceptibility or poses a significant health risk to crewmembers onboard the International Space Station. Immune system dysregulation has been documented during and after spaceflight, but it is not known if these changes increase infection susceptibility or pose a significant health risk to crewmembers. Inherent problems with current in-flight research are small sample sizes and the difficulty to control for the many confounding factors that impact on the immune system. As such, it is not known if changes in immunity are due to the microgravity environment per se, or to the stressors associated with landing and re-adaptation to the 1G environment. The present project will utilize a longitudinal repeated measures design to determine the effects of long-term exposure to microgravity on a host of salivary antimicrobial proteins (AMPs), latent viral reactivation, antibacterial properties of saliva, and blood markers associated with innate host immune defense, whilst also considering the impact of other acute stressors such as Soyuz landing. Saliva, urine and blood samples will be collected from crewmembers selected for ISS missions and ground-based controls pre-flight (L-180 and L-60 days), at “early”, “mid” and “late” phases during the approximately 5-6 month period on the ISS, and up to R+63 days after return to Earth. Subjects on yearlong missions will collect two “midpoint” samples. Saliva sampling was selected as the primary source because it is an excellent biological fluid with which to detect broad-spectrum biomarkers of front-line host immune defense and is suitable for the spaceflight environment. Attempts will also be made to establish relationships between salivary and cellular immune markers, viral reactivation and other stressors associated with spaceflight (i.e., mood state disturbances, circadian desynchronization, sleep loss/disruption, stress biomarkers) using serial data. Blood samples will be used for monocyte, NK-cell and neutrophil phenotype and functional assays. This project will help to establish if spaceflight alters innate immune function, which is important to determine if altered immunity poses a significant risk of an adverse health event among crewmembers. Moreover, these data will serve as a foundation for future countermeasure developments and technological advances to detect real time changes in immune function during subsequent lunar or Mars missions. 

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    Applications

    Space Applications

    The data obtained from this study will serve as a foundation for future countermeasure developments and technological advances to detect real time changes in immune function during subsequent lunar or Mars Missions.
     

    Earth Applications

    The data collected during this investigation may lead to a greater understanding of how the immune system is affected by different factors from stress to the environment. This data could potentially be used to help develop new treatments and preventative measures for immune dysfunctions.
     

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    Operations

    Operational Requirements

    Samples are required from 6 crewmembers.  Additionally, data will be collected before, during and after the yearlong mission of the US crewmember launching on 42S.  Subjects perform two sessions preflight (one at L-180 days and another at L-60 days), three sessions in-flight (FD10 +11/- 10 days, FD90 +30/- 50 days and R-1) and four sessions postflight (R+0, R+18, R+33 and R+63). Yearlong subjects will also perform an additional session at FD214 (±30 days). In-flight, urine and saliva samples are frozen in MELFI for later return. Blood will nominally be returned ambient; however, if a return vehicle is not available in the proper timeframe, a subset of the nominal samples will be collected, centrifuged and frozen in MELFI for later return. Ambient Blood samples must be returned to the PI for processing within 72 hours of collection, therefore, the blood draws must occur in conjunction with a Soyuz flight. 

    Operational Protocols

    Operations for this experiment consist of three types of sample collections: blood, urine and saliva early (FD10), mid (FD90), and late (R-1) in the mission. Subjects on yearlong missions will also collect samples for a second “midpoint” (FD214). Nominally, blood (four tubes, 29 ml total for six-month mission crewmembers; five tubes, 37.5 ml total for one-year mission crewmembers) will be placed into a sample pouch and returned ambient. If no return vehicle is available in the proper timeframe, a subset of the nominal samples (four tubes, 19 ml) will be collected, centrifuged, and then frozen in MELFI for later return. Three saliva samples are collected daily for seven days. Two of the samples are stored in bags and one is stored in a vial. Bagged saliva samples consist of the subject soaking a synthetic swab with saliva and placing the swab in a salivette bag.  The two bagged samples are each collected using a different method to soak the swab (one is placed sublingually and one is rolled in the mouth). Timed saliva samples are collected by soaking a synthetic swab with saliva for two minutes and placing that sample into a pre-weighed collection vial. All saliva samples are collected upon awakening and then frozen in MELFI.  The one-year mission crewmember will also collect dry book saliva samples (collected on filter paper bound in a small, specialized book at certain time intervals throughout the day) on the same day as each ambient blood draw (FD90, FD214, and R-1). The dry book samples will be returned ambient with the blood samples via Soyuz.  24-hour urine collections require the subject to collect all urine starting with the first void of the day and continuing for a full 24-hour period. A Health Assessment Questionnaire will be collected to document conditions related to immunology; such as allergies, rashes, hypersensitivities, infections and wound healing.

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    Results/More Information

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    Related Websites

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    Imagery