Characterization of the humoral and cellular immune responses to COVID-19 booster vaccination in multiple sclerosis patients receiving B-cell depleting anti-CD20 therapy (aCD20-MS). 

Vaccines against SARS-CoV-2 (CoV-2) have been efficient in blocking severe disease and death in immunocompetent and immunocompromised individuals. Nevertheless, aCD20-MS patients are at high risk of diminished vaccine response due to therapy-induced B-cell depletion. In contrast, a strong T-cell response after the initial two-dose vaccination has been observed in these individuals which could be at least partially responsible for their observed immune protection. The immune response to COVID-19 vaccine boosters in aCD20-MS patients remains largely unknown. 

Peripheral blood mononuclear cells (PBMCs) and serum samples were collected from aCD20-MS patients and healthy controls (HC) before and after COVID-19 booster vaccination. Humoral response was assessed by measuring receptor binding domain IgG antibody levels through an ELISA. For the cellular response, IFNγ⁺, IL-2⁺ and polyfunctional IFNγ⁺/IL-2⁺-secreting T-cells were quantified using a FluoroSpot assay after ex vivo stimulation of PBMCs with ancestral and Omicron versions of CoV-2 spike protein. 

Low seroconversion rates were observed in aCD20-MS patients, even after booster vaccinations. Contrary to the humoral response, spike-specific T-cell response was higher in aCD20-MS patients compared to HC after primary vaccination. Vaccine re-exposure significantly increased the cellular response only in HC (IFNγ⁺, fold induction: 3.7X; IL-2⁺: 2.1X; IFNγ⁺/IL-2⁺: 3.3X) but it still remained lower than the one detected in the aCD20-MS cohort (IFNγ⁺, aCD20-MS / HC ratio: 3.9; IL-2⁺: 1.6; IFNγ⁺/IL-2⁺: 2.1). Moreover, a 25% reduction in cellular response against Omicron spike was observed in both groups, suggesting a similar level of conservation.    

These results highlight that despite the potential development of a severely impaired humoral response in antiCD20-treated MS patients even after multiple COVID-19 vaccine doses, a sustained strong T-cell response might provide some level of immune protection against severe CoV-2 infection.