The impact of hybrid immunity on immune responses after SARS-CoV-2 vaccination in persons with multiple sclerosis treated with disease-modifying therapies.

BACKGROUND AND PURPOSE: Hybrid immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develops from a combination of natural infection and vaccine-generated immunity. Multiple sclerosis (MS) disease-modifying therapies (DMTs) have the potential to impact humoral and cellular immunity induced by SARS-CoV-2 vaccination and infection. The aims were to compare antibody and T-cell responses after SARS-CoV-2 mRNA vaccination in persons with MS (pwMS) treated with different DMTs and to assess differences between naïvely vaccinated pwMS and pwMS with hybrid immunity vaccinated following a previous SARS-CoV-2 infection. METHODS: Antibody and T-cell responses were determined in pwMS at baseline and 4 and 12 weeks after the second dose of SARS-CoV-2 vaccination in 143 pwMS with or without previous SARS-CoV-2 infection and 40 healthy controls (HCs). The MS cohort comprised natalizumab (n = 22), dimethylfumarate (n = 23), fingolimod (n = 38), cladribine (n = 30), alemtuzumab (n = 17) and teriflunomide (n = 13) treated pwMS. Immunoglobulin G antibody responses to SARS-CoV-2 antigens were measured using a multiplex bead assay and FluoroSpot was used to assess T-cell responses (interferon γ and interleukin 13). RESULTS: Humoral and T-cell responses to vaccination were comparable between naïvely vaccinated HCs and pwMS treated with natalizumab, dimethylfumarate, cladribine, alemtuzumab and teriflunomide, but were suppressed in fingolimod-treated pwMS. Both fingolimod-treated pwMS and HCs vaccinated following a previous SARS-CoV-2 infection had higher antibody levels 4 weeks after vaccination compared to naïvely vaccinated individuals. Antibody and interferon γ levels 12 weeks after vaccination were positively correlated with time from last treatment course of cladribine. CONCLUSION: These findings are of relevance for infection risk mitigation and for vaccination strategies amongst pwMS undergoing DMT.

AQP4 autoantibodies in patients with idiopathic normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a common neurological disorder with unknown etiology. A selective depletion of aquaporin 4 (AQP4) has been shown in iNPH patients. We collected serum and cerebrospinal fluid (CSF) from 43 iNPH patients and 35 with other neurodegenerative conditions, and serum from 43 healthy subjects. All samples were tested for AQP4-IgG/IgA/IgM antibodies using a live cell-based assay. No patients or controls had serum/CSF AQP4-IgG/IgA. One/43 iNPH patient and 0/43 controls tested positive for serum AQP4-IgM. The AQP4-IgM-positive iNPH patient had no clinico-radiological distinctive features. AQP4 antibodies are unlikely to play a role in iNPH pathogenesis.