Dynamic Evolution of Humoral and T-Cell Specific Immune Response to COVID-19 mRNA Vaccine in Patients with Multiple Sclerosis Followed until the Booster Dose

Abstract

This study characterizes antibody and T-cell immune responses over time until the booster dose of COronaVIrus Disease 2019 (COVID-19) vaccines in patients with multiple sclerosis (PwMS) undergoing different disease-modifying treatments (DMTs). We prospectively enrolled 134 PwMS and 99 health care workers (HCWs) having completed the two-dose schedule of a COVID-19 mRNA vaccine within the last 2–4 weeks (T0) and followed them 24 weeks after the first dose (T1) and 4–6 weeks after the booster (T2). PwMS presented a significant reduction in the seroconversion rate and anti-receptor-binding domain (RBD)-Immunoglobulin (IgG) titers from T0 to T1 (p < 0.0001) and a significant increase from T1 to T2 (p < 0.0001). The booster dose in PwMS showed a good improvement in the serologic response, even greater than HCWs, as it promoted a significant five-fold increase of anti-RBD-IgG titers compared with T0 (p < 0.0001). Similarly, the T-cell response showed a significant 1.5- and 3.8-fold increase in PwMS at T2 compared with T0 (p = 0.013) and T1 (p < 0.0001), respectively, without significant modulation in the number of responders. Regardless of the time elapsed since vaccination, most ocrelizumab- (77.3%) and fingolimod-treated patients (93.3%) showed only a T-cell-specific or humoral-specific response, respectively. The booster dose reinforces humoral- and cell-mediated-specific immune responses and highlights specific DMT-induced immune frailties, suggesting the need for specifically tailored strategies for immune-compromised patients to provide primary prophylaxis, early SARS-CoV-2 detection and the timely management of COVID-19 antiviral treatments.

Longitudinal study of immunity to SARS‐CoV2 in ocrelizumab‐treated MS patients up to 2 years after COVID‐19 vaccination

“…This is consistent with studies in the healthy population, where cellular immunity to COVID‐19 vaccination and infection tends to be more durable than antibody responses 46 . Robust longitudinal cellular immunity in B‐cell‐depleted MS patients is a consistent finding across multiple studies 28,36,47–50 . Booster further raised cytokine responses four to fivefold.…”

“…46 Robust longitudinal cellular immunity in B‐cell‐depleted MS patients is a consistent finding across multiple studies. 28 , 36 , 47 , 48 , 49 , 50 Booster further raised cytokine responses four to fivefold. This was a similar‐fold increase as after the primary vaccine.…”

Protecting the vulnerable: addressing the COVID-19 care needs of people with compromised immunity

“…This is due to multiple factors, including reduced T-cell–specific or humoral-specific responses, which leads to low seroconversion rates post-vaccination, generation of antibodies with low neutralization activity against SARS-CoV-2 ( 41 – 43 ), and a short duration of protection. Studies have shown that although alterations in the B-cell compartment correlate with decreased humoral responses to COVID-19 vaccines, some degree of T-cell–mediated protection from severe disease might be conserved ( 23 , 44 , 45 ). A meta-analysis of 82 studies ( 46 ) showed that after one vaccine dose, people with hematological cancers, immune-mediated inflammatory disorders, and solid cancers were half less likely to seroconvert, while transplant recipients were 16 times less likely to seroconvert (risk ratio 0.06 [95% CI 0.04–0.09]) compared with immunocompetent controls.…”

COVID-19 Pandemic: Therapeutic Strategies and Vaccines

“…Ruggieri’s article focuses on characterizing the immune responses, including antibodies and T-cells, in patients with multiple sclerosis (PwMS) who are receiving various disease-modifying treatments (DMTs) after receiving COVID-19 vaccines [ 44 ]. A total of 134 PwMS and 99 healthcare workers (HCWs) who had completed the two-dose COVID-19 mRNA vaccine schedule within the last 2–4 weeks (T0) were prospectively enrolled.…”