T cell responses to SARS-CoV-2 vaccination differ by disease-modifying therapy for multiple sclerosis

Area of Science:

• Immunology
• Neuroscience
• Virology

Background:

• Multiple sclerosis (MS) patients on disease-modifying therapies (DMTs) have altered immune responses, particularly relevant during the COVID-19 pandemic.
• Lymphocyte-targeting DMTs like anti-CD20 and S1PR modulators can reduce antibody (Ab) responses post-vaccination.
• Assessing cellular immunity, specifically T cell responses, is crucial in these populations after vaccination.

Purpose of the Study:

• To analyze CD4 and CD8 T cell functional responses to SARS-CoV-2 spike peptides in healthy controls and MS patients on various DMTs.
• To compare T cell responses in MS patients receiving rituximab and fingolimod after COVID-19 vaccination.
• To evaluate T cell responses against different SARS-CoV-2 variants (Delta, Omicron) compared to the ancestral strain.

Main Methods:

• Flow cytometry was used to analyze CD4 and CD8 T cell functional responses.
• Study included healthy controls and MS patients on five different DMTs.
• SARS-CoV-2 spike peptides from ancestral and variant strains were used for stimulation.

Main Results:

• MS patients on rituximab showed preserved T cell responses after a third vaccine dose, even with an additional rituximab dose.
• MS patients on fingolimod exhibited low detectable T cell responses in peripheral blood.
• T cell responses to SARS-CoV-2 Delta and Omicron variants were lower than to the ancestral Wuhan-Hu-1 variant.

Conclusions:

• Vaccination can elicit immune responses in MS patients, even with diminished antibody production.
• Assessing both cellular (T cell) and humoral (antibody) responses is vital for understanding vaccine effectiveness in MS patients on DMTs.
• Rituximab therapy may preserve T cell immunity post-vaccination in MS patients, while fingolimod shows limited T cell response.