Short Title: Anti-viral Drug

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

1. To study the effect of antiviral drugs on the reactivation and shedding of varicella zoster virus (VZV) in the saliva of Antarctic expeditioners before, during and after winter-over.

2. To study the effect of antiviral drugs on stress hormones and immune biomarkers (inflammatory

cytokines, etc.) in the saliva of Antarctic expeditioners before, during and after winter-over.

Short Title: NK cells CM

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
SA1: Determine the effect of simulated microgravity on the anti-tumor capacity of human NK-cells and γδ-T cells in vivo. Experimental Approach: We will use our established rotating cell culture model to expose human PBMCs, expanded NK-cells or expanded γδ-T cells to simulated microgravity or controls (static-1G and rotational control) prior to adoptive transfer into human tumor bearing NOD-scid-IL2Rγnull (NSG) mice. The NSG mice will be engrafted with a human luciferase-labelled human leukemia cell line (K562), as blood cancers are considered a risk for long duration exploration crew. The NSG mice will also be engrafted with an NK-cell sensitive solid tumor (human neuroblastoma; SK-N-SH cell line) which will enable us to study tumor infiltrates by isolating tissues and quantifying the human immune cells in the tumor by multi-parameter flow cytometry. Spectral imaging (LagoX) will be utilized to measure tumor progression and dissemination of the luciferase-tagged human cancer cell lines. Hypothesis: Exposure to simulated microgravity will have an adverse effect on the in vivo dynamics of human NK and γδ-T cells, impairing their ability to infiltrate and control human tumor growth in a humanized rodent model.

SA2: Determine the effect of systemic administration of IL-2 and ZOL on the function of NK and γδ-T cells respectively. Experimental Approach: NSG mice adoptively transferred with human PBMCs, NK-cells and γδ-T cells will be infused with zoledronic acid (ZOL) and IL-2 as a potential countermeasure to microgravity-induced immune system impairment. ZOL and IL-2 are currently used clinically to increase the proliferation and function of NK-cells and γδ-T cells in bone marrow transplant patients to prevent disease relapse. Hypothesis: Systemic administration of IL-2 and ZOL will ‘rescue’ the in vivo anti-tumor activity of human NK-cells and γδ-T cells following their exposure to simulated microgravity. 

Short Title: Immune CM Validation – Palmer

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Directed

Aims:
1. To determine if the complete immune countermeasure protocol developed for spaceflight ameliorates the effect of coastal Antarctica winterover, as a relevant ground-analog for deep space missions, on salivary stress hormones, salivary cytokine profiles, and the incidence of latent herpesvirus reactivation and shedding.

2. To determine if the complete immune countermeasure protocol mitigates the perturbations to the immune system caused by an Antarctic winter-over mission. Specifically, we will determine if the countermeasure prevents fluctuations in phenotype frequency and depression in cellular function (T, NK, B, monocytes, dendritic). The concentrations of a variety of other factors associated with immunity, including relevant nutritional analytes, markers of oxidative damage, and inflammation, will also be monitored.