Valacyclovir reduces inflammation and IgG subclass activation by suppressing herpesvirus reactivation in antarctic expeditioners

Astronauts experience a higher frequency and greater magnitude of latent herpesvirus reactivation than the general population during and after space travel. This is likely due to space-related physiological and psychological stressors. Repeated symptomatic or asymptomatic viral reactivations may further increase immune burden and contribute to persistent low-grade inflammation and immune dysregulation, highlighting the need for effective countermeasures during long duration missions. In our previous randomized, placebo-controlled trial in Antarctic expeditioners, we demonstrated that daily administration of valacyclovir (1g/day) markedly reduced both the frequency and load of Epstein-Barr virus (>24fold) and herpes simplex virus-1 (>4fold). Using the saliva supernatants from this published parent study, the present brief research report examines salivary C-reactive protein (CRP) and immunoglobulins A, G1-4, and M to further characterize downstream immune effects of antiviral suppression.

Detailed participant information, saliva sampling procedures, and the study timeline are described in the previous manuscript. Residual frozen saliva supernatants from the original study were analyzed for CRP (Salimetrics) and immunoglobulins IgA, IgM, and IgG1-4 (Millipore Sigma), according to manufacturer instructions.

CRP concentrations were significantly lower in the valacyclovir group compared with the placebo group across the mission. IgG subclasses demonstrated clear treatment effects: IgG1, IgG3, and IgG4 were reduced in the valacyclovir group, while IgG2 remained unchanged. IgA and IgM showed no overall differences between groups.

Suppressing latent herpesvirus reactivation with valacyclovir reduces inflammatory and humoral immune activation in Antarctic expeditioners. These findings advance the understanding of virus-driven immune dysregulation and support antiviral prophylaxis as a potential countermeasure for maintaining immune stability during long-duration spaceflight.