ABSTRACT
Introduction: Some MS DMTs, such as anti-CD20 antibodies and sphingosine-1-phosphate (S1P) receptor modulators, decrease post-infection and post-vaccination SARS-Cov-2 humoral responses. However, humoral immunity is only one component of the adaptive response, and T cell responses, which may be preserved in anti-CD20 treated patients, play an important role. Objective(s): To characterize SARS-Cov-2 spike specific memory T-cell receptor repertoires in patients with MS and related conditions post-vaccination with mRNA vaccines. Aim(s): To characterize SARS-Cov-2 vaccine-mediated responses for people using MS DMTs. Method(s): Patients without prior COVID-19 infection provided a whole blood sample >3 weeks and <6 months after vaccination with two doses of Pfizer-BioNTech or Moderna mRNA vaccines. Sequencing of the complementary determining region within T-cell receptors (TCRs) was performed. Antigen recognition activates unique TCRs and results in expansion of antigen-specific T-cell clones. Sample TCR sequences were cross-matched with sequences known to react to SARS-CoV-2 using "Multiplex Identification of T-cell Receptor Antigen Specificity (MIRA)", allowing for characterization of SARS-CoV-2-spike-specific TCR frequency (clonal depth) and diversity (clonal breadth). Humoral responses were compared. Result(s): 39 patients were recruited: age 25-77;27 female;37 with MS, 2 with NMO, and 1 with another neuroimmune condition. DMTs included anti-CD20 (N=13), natalizumab (N=9), fumarates (N=8), S1P receptor modulators (N=3), and controls (2 glatiramer acetate, 4 no DMT). Mean time interval between 2nd vaccination dose and TCR testing was 13.3+6.0 weeks. Humoral responses (Roche) were absent in all anti-CD20 and S1P treated patients but preserved in all others. SARS-CoV-2-spikespecific clonal depth and breadth did not differ across all treatment classes except S1P modulators. Despite lack of antibody production, patients treated with anti-CD20 therapies demonstrated comparable TCR depth and breadth to all other groups in univariable assessment. No spike-specific TCRs were found in patients treated with S1P modulators. TCR breadth and depth did not vary with time since vaccination even up to 24 weeks following vaccination. Conclusion(s): TCR repertoires were preserved except for in those treated with S1P receptor modulators.Humoral responses were diminished with both anti-CD20 and S1P DMTs. These findings may help guide counseling of patients with regards to DMT choice.