NOTE: End date changed to 10/1/2022 per L. Singh/HRP JSC (Ed., 4/8/21)

These findings will indicate if valacyclovir treatment will reduce or stop viral reactivation and its shedding in saliva. This will enhance the selection and vetting of potential countermeasures to address clinical risks associated with reduced immune function. This will improve crew health care on International Space Station (ISS) missions, and will further enable exploration-class missions.

Reactivation and shedding of herpes viruses such as Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV1), varicella zoster virus (VZV), and cytomegalovirus (CMV) increase in astronauts during spaceflight as compared to their preflight and postflight levels. These potential reactivation events increase the risk of associated clinical conditions like herpes zoster, chronic neuropathic pain, vision loss, stroke, cognitive impairment, and cold sores. Furthermore, continued viral shedding for a longer period after space travel may increase the risk of transmitting the virus to crew contacts who are uninfected with the virus – including, but not limited to, the immunocompromised or to newborn infants. Thus, it is essential to develop spaceflight countermeasures to prevent reactivation of these herpes viruses, ensuring the health of the crewmembers and their contacts upon return. One such countermeasure is prophylactic administration of an antiviral drug (valacyclovir) against the alpha herpesviruses (VZV, HSV-1). To determine the effectiveness of this countermeasure using a large population, we studied shedding of EBV, VZV and HSV-1 in Antarctic expeditioners (who have been reported to have similar viral shedding patterns in their saliva during winter-over as astronauts during long spaceflights). Countermeasure efficacy of this antiviral drug was determined by 3 major parameters, including viral load, physiological stress biomarkers (cortisol, DHEA, and amylase) and immune markers (inflammatory cytokines) during the winter-over in the saliva of expeditioners with and without administration of this drug. Thirty-two volunteers from two Antarctic stations (McMurdo and South Pole) participated in this study. Subjects were randomly assigned to either treatment group (valacyclovir HCl: 1 g/day), or placebo group (oyster Calcium 500mg/day). EBV and HSV-1 viral shedding was significantly reduced in the treatment group versus the placebo group by >24 fold (EBV) and >5 fold (HSV1) over the course of winter-over period. No VZV shedding was seen in any of the subjects. 50% of the placebo saliva samples had measurable viral DNA (either EBV, HSV1, or both) compared to 19% of the treatment group. There was no significant change in the Cortisol to DHEA ratio or alpha amylase, indicating physiological stress was similar between the groups. No difference was detected in salivary cytokines except IL-10, which was significantly lower in the treatment group than the placebo group. These data indicate that valacyclovir (1g/day) is a safe and successful intervention to reduce herpes virus reactivations and shedding in individuals subjected to extreme environments and stressors.

These findings will indicate if valacyclovir treatment will reduce or stop viral reactivation and its shedding in saliva. This will enhance the selection and vetting of potential countermeasures to address clinical risks associated with reduced immune function. This will improve crew health care on International Space Station (ISS) missions, and will further enable exploration-class missions.

Background and Significance: In a recent collaborative study with Dr. Alexander Chouker (European Space Agency-ESA physician researcher), 19 subjects at Concordia Station in Antarctica were examined during overwintering for their latent viral reactivation and shedding patterns in their saliva samples collected each month for before, during, and after winter-over period. VZV DNA was found by real time polymerase assay in 10 out of 19 subjects (52%) with most of the shedding occurring during the study than before or afterwards. This is about the same rate of VZV shedding as we have found in astronauts during short and long duration spaceflights (50-65%). This data provide the motivation for this proposal, i.e., that wintering over in Antarctica is an excellent analog to spaceflight for studying the efficacy of a countermeasure against viral shedding. More specifically, we can study the effect of antiviral agents (e.g., valacyclovir) during an Antarctica winterover and apply lessons learned to upcoming spaceflight missions. This might allow us to prevent viral shedding in astronauts and thus reduce the risk of contaminating the internal environment of the spacecraft with infectious viruses, as well as decreasing their risk of associated VZV diseases including zoster, chronic neuropathic pain, vision loss, stroke and cognitive impairment.

Hypothesis: Prophylactic administration of valacyclovir (1 gram daily) to Antarctic expeditioners will significantly reduce salivary shedding of VZV compared to placebo controls. Measures of stress and immune dysregulation should remain unaltered. To test this hypothesis, we will treat 20 expeditioners with daily valacyclovir and another 20 with placebo and measure VZV DNA (as well as other herpesviruses) before, during, and after the expedition.

Study Population

* General description of the study population: Antarctica expeditioners

* Target number of non-astronaut participants: Total 40: 20 experimental, 20 Placebo

Saliva samples

* About 900 human saliva samples (2 ml each) were collected in total throughout the winter season at McMurdo and 500 samples were collected from South Pole.

* Samples were maintained at -80°C during shipping and received in the Immunology and Virology Lab of Johnson Space Center.

Future plan: A detailed inventory of the samples collected from both McMurdo and South Pole will be done and a plan will be drawn to process these samples as described in the original proposal.

These findings will indicate if valacyclovir treatment will reduce or stop viral reactivation and its shedding in saliva. This will enhance the selection and vetting of potential countermeasures to address clinical risks associated with reduced immune function. This will improve crew health care on International Space Station (ISS) missions, and will further enable exploration-class missions.