Transient clinical improvement and immune modulation following recombinant Zoster vaccination in a patient with ME/CFS

Introduction Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem disorder associated with immune dysregulation yet lacks definitive biomarkers or effective therapies. Acute immune perturbations may transiently modulate disease manifestations. Methods We report the case of a female patient in her 60s with severe, long-standing ME/CFS who experienced changes in symptom following administration of recombinant zoster vaccine (RZV; Shingrix). Peripheral blood mononuclear cells were analyzed pre- and post-vaccination using flow cytometry, with comparison to a female healthy control. Plasma galectin-9 (Gal-9) levels were quantified by ELISA. Results Both RZV doses were associated with rapid, transient remission of symptoms, including improved sleep, cognition, pain, mobility, and respiratory function, followed by relapse. Immunologically, pre-vaccination profiling revealed elevated monocytes, increased CD71 + erythroid cells, and features of T cell exhaustion marked by Gal-9/PD-1 co-expression and impaired cytokine responses. Post-vaccination, monocyte frequency decreased, Gal-9 + /PD-1 + T cells were reduced, and NK cell degranulation improved, indicating partial restoration of immune function. Conclusion This case demonstrates that immune stimulation via RZV may transiently reverse immune dysfunction and improve clinical symptoms in ME/CFS. These findings support a role for reversible immune exhaustion in disease pathogenesis and highlight potential avenues for biomarker development and therapeutic intervention.