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

Abstract:

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.

Source: Bigleri A, Alimo ET, Abouda A, Osman M, Cohen Tervaert JW, Elahi S. Transient clinical improvement and immune modulation following recombinant Zoster vaccination in a patient with ME/CFS. Brain Behav Immun Health. 2026 Oct 13;58:101388. doi: 10.1016/j.bbih.2026.101388. PMID: 42927120; PMCID: PMC13694728. https://pmc.ncbi.nlm.nih.gov/articles/PMC13694728/ (Full text)

Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis

Abstract:

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), long COVID (LC) and post-COVID-19 vaccine syndrome show similarities in their pathophysiology and clinical manifestations. These disorders are related to viral or adjuvant persistence, immunological alterations, autoimmune diseases and hormonal imbalances.

A developmental model is postulated that involves the interaction between immune hyperactivation, autoimmune hypophysitis or pituitary hypophysitis, and immune depletion. This process might begin with a deficient CD4 T-cell response to viral infections in genetically predisposed individuals (HLA-DRB1), followed by an uncontrolled immune response with CD8 T-cell hyperactivation and elevated antibody production, some of which may be directed against autoantigens, which can trigger autoimmune hypophysitis or direct damage to the pituitary, resulting in decreased production of pituitary hormones, such as ACTH. As the disease progresses, prolonged exposure to viral antigens can lead to exhaustion of the immune system, exacerbating symptoms and pathology.

It is suggested that these disorders could be included in the autoimmune/adjuvant-induced inflammatory syndrome (ASIA) because of their similar clinical manifestations and possible relationship to genetic factors, such as polymorphisms in the HLA-DRB1 gene. In addition, it is proposed that treatment with antivirals, corticosteroids/ginseng, antioxidants, and metabolic precursors could improve symptoms by modulating the immune response, pituitary function, inflammation and oxidative stress.

Therefore, the purpose of this review is to suggest a possible autoimmune origin against the adenohypophysis and a possible improvement of symptoms after treatment with corticosteroid replacement therapy.

Source: Manuel Ruiz-Pablos, Bruno Paiva, Aintzane Zabaleta. Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis. Front. Immunol., 08 July 2024, Sec. Viral Immunology, Volume 15 – 2024 | https://doi.org/10.3389/fimmu.2024.1422940 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1422940/full (Full text)