Effect of dynamics and timing of SARS-CoV-2 vaccination on immune response in people with multiple sclerosis during cladribine treatment.

Since the onset of the COVID-19 pandemic, the World Health Organization has recommended vaccination for people with multiple sclerosis (pwMS). However, vaccine-induced immune responses in pwMS receiving immunomodulatory therapies are currently poorly characterized. Herein, we evaluated humoral and T cell-mediated immune responses against BNT162b2 mRNA vaccine in pwMS treated with cladribine (n = 30), focusing on how the time interval between drug administration and vaccination affects the magnitude and dynamics of vaccine-induced immune response. We found that cladribine influenced both B and T cell frequencies with different kinetics over time. Accordingly, vaccination after cladribine administration resulted in reduced antibody production but preserved T cell responses, whereas pwMS receiving vaccine before cladribine exhibited an effective humoral immunity but hampered SARS-CoV-2 Spike-specific T cell response. Our findings may inform the clinical decision-making process by providing evidence to support the identification of an appropriate time window for vaccination during cladribine treatment.