Humoral and cell-based responses following SARS-CoV-2 mRNA vaccination of patients with multiple sclerosis on B-cell depleting therapy

Introduction: Anti-CD20 treated MS patients may have higher risk of severe SARS-CoV-2. Early reports indicate they mount attenuated antibody responses to SARS-CoV-2 vaccines, raising significant concerns about their protection, and the merit of aCD20 infusion delay to enable more robust vaccine responses. Little is known about cellular responses (particularly spike-antigen-specific T-cell responses) to these vaccines in B cell-depleted state. Aims: To characterize the magnitude and kinetics of both antibody-and cell-based responses to SARS-CoV-2 mRNA vaccines in aCD20 treated MS patients, compared to healthy controls (HC). Methods: Both humoral IgG responses to Spike (S) protein and its receptor-binding-domain (RBD), as well as Spike-reactive B cells (flow cytometry) and S-protein-specific CD4+ and CD8+ T-cell responses (activation-induced marker/AIM assays), were serially assessed in 21 MS patients on aCD20 therapy and 10 HC, pre-and post-SARS-CoV-2 mRNA vaccination (pre-vaccine-T1;10 days post primary-T2, pre-booster-T3;10-day post-booster-T4 and 30 days post-booster-T5). Results: Antibodies to both S-protein and RBD were induced in 100% of HC by T4 and, with some lag (by T5), in 89% and 50% of MS patients, respectively. Mean Spike-IgG concentrations for HC and MS patients at T5 were 165.3± 201.9 units/mL (u/ml) and 22.3± 58.2 u/mL respectively (p=0.0004);and 97± 136 u/ mL(HC) and 10.2± 29 u/mL (MS) (p<0.0001) for RBD-IgG. All 6 patients vaccinated longer than 20 weeks after the last aCD20 treatment exhibited partial B-cell reconstitution, and all had measurable spike-specific memory B-cells at T5. All MS patients and HC mounted CD4+ and CD8+ T-cell responses to vaccine. Expansion of activated (Ki67+CD38+) CD4+ T-cells was robust in HC and somewhat attenuated in MS patients (p= 0.03), while expansion of activated (Ki67+CD38+) CD8+ T cells was robust in both cohorts. In AIM assays, spike-antigen-specific responses of CD4+ T-cells of patients were similarly mildly attenuated compared to HC, while those of CD8+ T cells were similarly robust for both patients and HC. Conclusion: In spite of attenuated humoral SARS-CoV-2 mRNA vaccine responses, aCD20 treated patients mount robust CD8+ and mildly attenuated CD4+ T-cell responses. Longer time from last aCD20 infusion may enable more robust humoral and cell-based responses. It will be important to study how cell-based responses relate to protection, complications and risk of infecting others.

The Geopolitics of the Yemen War during the Corona Pandemic: An Althusserian Approach

This article addresses the geopolitics of Bab-al-Mandeb in the war on Yemen, which began in 2015 and continues to this day, in the context of a global pandemic. It makes the hypothesis that securing Bab-al-Mandeb is fundamental for US imperialism. For reasons to do with its global hegemony, the United States cannot permit another force, specifically the Houthis of Yemen, to exercise control over Bab-al-Mandeb. Although many reasons could account for the senseless war, the security of Bab-al-Mandeb-a strategic chokepoint of trade and oil flows-over-determinedly (as in an Althusserian concept) explains the war's continuity. © 2020 University of California Press. All rights reserved.