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Gap IM1: We do not know to what extent spaceflight alters various aspects of human immunity during spaceflight missions up to 6 months.
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Last Published:  07/31/19 10:05:30 AM (Central)
Responsible Element: Human Health Countermeasures (HHC)
Status: Open
Description

Initial  State:  At the 2005 inception of the HRP there was little known about the in-flight status of the human immune system.  A wealth of knowledge defined immune dysregulation post-flight, including diminished cellular function, dysregulated cytokine production profiles and physiological stress.  However, it was generally unknown if these observations reflected the in-flight condition.  Several narrow-focus, low ‘n’ in-flight studies did indicate that immune dysregulation could be an in-flight phenomenon, however proper investigation of the various aspects of immunity and stress (innate/adaptive, humoral/cellular, dysfunction among specific cell types, etc.) was lacking.   The reactivation of latent herpesviruses, thought to be a direct consequence of diminished immune function, was well established during short duration spaceflight, but it was unknown if this phenomenon would persist or resolve during long-duration spaceflight.   It is generally believed that such dysregulation would not be a significant clinical risk for orbital flight (despite incidence of immune-related health events on orbit), but that persistent dysregulation could pose a crew health risk during exploration class deep-space missions.  During the intervening period since HRP inception, Integrated Immune has thoroughly characterized certain aspects of adaptive immunity and viral reactivation during short- and long-duration spaceflight.   The new findings confirm that both immune dysregulation and latent herpesvirus reactivation persist during 6-month ISS missions.   Other aspects of immunoreguation remain relatively uninvestigated during spaceflight.   [NOTE:  A thorough compilation of the immune evidence base is available in the 2013 rewrite of the HRP Evidence Book, Immunology Chapter] 


Intermediate Steps/Metrics:  Analysis of data to determine immune parameters to measure in flight. 

 

  1. Baseline data characterizing those properties of adaptive immunity and herpes virus reactivation during spaceflight  assayed by the Integrated Immune and Immuno flight studies, included leukocyte distribution, T cell function, cytokine production profiles for adaptive immune cells (T cells, etc.) along with herpesvirus reactivation.   At study completion, Gap closure ~35%. 

  2. Characterize aspects of innate immunity, as defined by those properties assayed by the Salivary Markers flight study, which will assess the distribution and function of innate immune cells (monoyctes, macrophages, dendritic cells, etc.).   At study completion, Gap closure ~45%. 

  3. Characterize other uninvestigated aspects of immunoregulation, stress, virology and crew incidence, including some specific SRP recommendations.  This is planned to be accomplished via a large integrated multi-laboratory internal/external study during the lifespan of ISS. Specific assays will be determined by immune SRP inputs, relevant NASA board inputs, the solicitation process, peer review process, and final approval.This study should essentially close Gap IM-01 (post completion status ~95%).

  4. The remaining ~5% Gap allows for emergent breakthroughs in immunology that occur during the lifespan of these studies.

Approach:  Measurement and characterization of selected immune biomarkers (leukocyte distribution, cellular function, cytokine profiles, etc.) before, during, and after spaceflight.   Specific plan will be to complete the Salivary Markers flight study, propose and gain approvals for subsequent large follow-up study, execute to completion prior to decommissioning of ISS.

Target for Closure
This Gap will close when the effects of spaceflight on human immunity (innate and adaptive) are understood sufficient to interpret clinical risk and the necessity of countermeasures. This determination should be made by a panel comprised of flight surgeons, clinical immunologists, and members of the space-immunology research community.
Mappings
Risk Risk of Adverse Health Event Due to Altered Immune Response
You are here! Gap IM1: We do not know to what extent spaceflight alters various aspects of human immunity during spaceflight missions up to 6 months.
Active
Task Space Biochemistry Profile
Task Functional immune alterations, latent Herpesvirus reactivation, physiological stress and clinical incidence onboard the International Space Station
Task Assessing Telomere Lengths and Telomerase Activity in Astronauts
Task Effects of space flights on the proteome of astronauts' plasma (Rithidech) functional immune
Task DNA damage in the ISS astronaut's lymphocytes and their association with stress-induced immune dysfunction (Honglu Wu) Functional immune
Task The impact of an ISS mission on the anti-viral and functional properties of NK-cells, T-cells, B-cells and dendritic cells (Simpson) Functional immune
Task The impact of long duration spaceflight on the function of B-cells and biomarkers of inflammation (Spielmann)
Task Spaceflight-Induced Changes in Microbial Virulence and the Impact to the Host Immune Response
Task The impact of modeled microgravity and prior radiation exposure on cytomegalovirus reactivation and host immune evasion
Task Monitoring the Cellular Immunity by in vitro Delayed Type Hypersensitivity Assay on ISS
Completed
Completed Task Flight-Induced Changes in Immune Defenses-DSO 498
Completed Task Incidence of Latent Virus Shedding During Space Flight-DSO 493
Completed Task Nutritional Status Assessment: SMO-016E
Completed Task Space Flight-Induced Reactivation of Latent Epstein-Barr Virus
Completed Task The Effects of Long-Term Exposure to Microgravity on Salivary Markers of Innate Immunity
Completed Task Validation of Procedures for Monitoring Crewmember Immune Function (Integrated Immune - SMO 015/SDBI 1900) Completed
Completed Task Examination of Splenic and Thymic Immune Function in Mice (STS-135 Mouse Tissue Sharing Pilot Study)
Completed Task Microbial Risk Assessment and Integration
Planned-Funded
Task Immune Countermeasures Validation - Flight
Terminated
Task Deep Space Exploration Atmosphere Effects on Hematologic, Immunologic, and Oxidative Stress and Damage Parameters in Astronauts: An ISS Flight Study

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