tetano
Editor, Senior Moderator
Front Immunol
. 2025 Oct 30:16:1682049.
doi: 10.3389/fimmu.2025.1682049. eCollection 2025. Minimal association between Th1-specific responses to COVID-19 vaccines and SARS-CoV-2 breakthrough infections in multiple sclerosis patients receiving disease-modifying therapies
Alessandra Aiello[SUP] 1 [/SUP], Assunta Navarra[SUP] 2 [/SUP], Shalom Haggiag[SUP] 3 [/SUP], Serena Ruggieri[SUP] 3 [/SUP], Gilda Cuzzi[SUP] 1 [/SUP], Valentina Vanini[SUP] 1 4 [/SUP], Andrea Salmi[SUP] 1 [/SUP], Stefania Notari[SUP] 5 [/SUP], Anna Maria Gerarda Altera[SUP] 1 [/SUP], Silvia Meschi[SUP] 6 [/SUP], Francesca Colavita[SUP] 6 [/SUP], Eleonora Cimini[SUP] 5 [/SUP], Carla Tortorella[SUP] 3 [/SUP], Luca Prosperini[SUP] 3 [/SUP], Maria Esmeralda Quartuccio[SUP] 3 [/SUP], Simonetta Galgani[SUP] 3 [/SUP], Vincenzo Puro[SUP] 7 [/SUP], Fabrizio Maggi[SUP] 6 [/SUP], Alba Grifoni[SUP] 8 [/SUP], Alessandro Sette[SUP] 8 9 [/SUP], Emanuele Nicastri[SUP] 10 [/SUP], Claudio Gasperini[SUP] 3 [/SUP], Delia Goletti[SUP] 1 [/SUP]
Affiliations
Background: The COVID-19 pandemic highlighted challenges in managing patients with multiple sclerosis (PwMS), as disease-modifying therapies (DMTs) can interfere with immune responses to infections and vaccines.
Objective: This study investigates the spike-specific T-cell response after the third dose of mRNA COVID-19 vaccines in PwMS undergoing DMTs, evaluating different cytokines, beyond IFN-γ, and exploring their potential association with SARS-CoV-2 breakthrough infections (BI).
Methods: We prospectively enrolled 31 PwMS and 27 healthcare workers (HCWs). The spike-specific T-cell response was evaluated by measuring Th1 cytokines (IFN-γ, IL-2, TNF-α) and IP-10 using an easy-to-use whole-blood assay.
Results: Most PwMS mounted a Wuhan spike-specific T-cell response by releasing Th1 cytokines (IFN-γ, IL-2, TNF-α) and IP-10, albeit with significantly reduced Th1 cytokine levels compared to HCWs. Fingolimod-treated patients showed the weakest response with significantly reduced IFN-γ and IL-2 levels compared to HCWs (both p<0.0001), as well as to ocrelizumab (p=0.0018 and p=0.0002, respectively) and cladribine/IFN-β-treated patients (p=0.041 and p<0.0001, respectively). Moreover, a cell-mediated response was observed against the Delta spike variant, and all cytokines correlated with each other. BI occurred in 38.7% of PwMS, with predominantly mild COVID-19 cases. Male sex (IRR: 4.05, p=0.017) and primary progressive MS (IRR: 3.65, p=0.052) were associated with a higher BI incidence rate. Spike-specific T-cell response did not associate with a higher protection against BI.
Conclusions: This study provides an in-depth immunological characterization of the spike-specific T-cell response in PwMS under DMTs, evaluating immunological biomarkers whose relevance may extend beyond COVID-19 for studying immune responses to other infections and vaccinations.
Keywords: SARS-CoV-2 infection; T-cell response; Th1 cytokines; disease-modifying therapies; mRNA vaccines; multiple sclerosis.
. 2025 Oct 30:16:1682049.
doi: 10.3389/fimmu.2025.1682049. eCollection 2025. Minimal association between Th1-specific responses to COVID-19 vaccines and SARS-CoV-2 breakthrough infections in multiple sclerosis patients receiving disease-modifying therapies
Alessandra Aiello[SUP] 1 [/SUP], Assunta Navarra[SUP] 2 [/SUP], Shalom Haggiag[SUP] 3 [/SUP], Serena Ruggieri[SUP] 3 [/SUP], Gilda Cuzzi[SUP] 1 [/SUP], Valentina Vanini[SUP] 1 4 [/SUP], Andrea Salmi[SUP] 1 [/SUP], Stefania Notari[SUP] 5 [/SUP], Anna Maria Gerarda Altera[SUP] 1 [/SUP], Silvia Meschi[SUP] 6 [/SUP], Francesca Colavita[SUP] 6 [/SUP], Eleonora Cimini[SUP] 5 [/SUP], Carla Tortorella[SUP] 3 [/SUP], Luca Prosperini[SUP] 3 [/SUP], Maria Esmeralda Quartuccio[SUP] 3 [/SUP], Simonetta Galgani[SUP] 3 [/SUP], Vincenzo Puro[SUP] 7 [/SUP], Fabrizio Maggi[SUP] 6 [/SUP], Alba Grifoni[SUP] 8 [/SUP], Alessandro Sette[SUP] 8 9 [/SUP], Emanuele Nicastri[SUP] 10 [/SUP], Claudio Gasperini[SUP] 3 [/SUP], Delia Goletti[SUP] 1 [/SUP]
Affiliations
- PMID: 41246331
- PMCID: PMC12611814
- DOI: 10.3389/fimmu.2025.1682049
Background: The COVID-19 pandemic highlighted challenges in managing patients with multiple sclerosis (PwMS), as disease-modifying therapies (DMTs) can interfere with immune responses to infections and vaccines.
Objective: This study investigates the spike-specific T-cell response after the third dose of mRNA COVID-19 vaccines in PwMS undergoing DMTs, evaluating different cytokines, beyond IFN-γ, and exploring their potential association with SARS-CoV-2 breakthrough infections (BI).
Methods: We prospectively enrolled 31 PwMS and 27 healthcare workers (HCWs). The spike-specific T-cell response was evaluated by measuring Th1 cytokines (IFN-γ, IL-2, TNF-α) and IP-10 using an easy-to-use whole-blood assay.
Results: Most PwMS mounted a Wuhan spike-specific T-cell response by releasing Th1 cytokines (IFN-γ, IL-2, TNF-α) and IP-10, albeit with significantly reduced Th1 cytokine levels compared to HCWs. Fingolimod-treated patients showed the weakest response with significantly reduced IFN-γ and IL-2 levels compared to HCWs (both p<0.0001), as well as to ocrelizumab (p=0.0018 and p=0.0002, respectively) and cladribine/IFN-β-treated patients (p=0.041 and p<0.0001, respectively). Moreover, a cell-mediated response was observed against the Delta spike variant, and all cytokines correlated with each other. BI occurred in 38.7% of PwMS, with predominantly mild COVID-19 cases. Male sex (IRR: 4.05, p=0.017) and primary progressive MS (IRR: 3.65, p=0.052) were associated with a higher BI incidence rate. Spike-specific T-cell response did not associate with a higher protection against BI.
Conclusions: This study provides an in-depth immunological characterization of the spike-specific T-cell response in PwMS under DMTs, evaluating immunological biomarkers whose relevance may extend beyond COVID-19 for studying immune responses to other infections and vaccinations.
Keywords: SARS-CoV-2 infection; T-cell response; Th1 cytokines; disease-modifying therapies; mRNA vaccines; multiple sclerosis.