Immunological Response to COVID-19 Vaccine Boosters in Multiple Sclerosis Patients Treated with anti-CD20 Therapy (S21.001)

Abstract

<h3>Objective:</h3> 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). <h3>Background:</h3> 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. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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. <h3>Conclusions:</h3> 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. <b>Disclosure:</b> Antonia De Oliveira has nothing to disclose. Miss Lei has nothing to disclose. Ms. Liu has nothing to disclose. Ms. Roche has nothing to disclose. Mr. Lin has nothing to disclose. Mr. Alfonso has nothing to disclose. Dr. Sadiq has nothing to disclose.