Three to four mRNA COVID‐19 vaccines in multiple sclerosis patients on immunosuppressive drugs: Seroconversion and variant neutralization

Abstract

Background and purpose An enhanced severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine regimen could improve humoral vaccine response in patients with multiple sclerosis (MS) treated by anti‐CD20. The aim was to evaluate the serological response and the neutralizing activity after BNT162b2 primary and booster vaccination in MS patients, including patients on anti‐CD20 receiving a primary vaccine regimen enhanced with three injections. Methods In this prospective longitudinal cohort study of 90 patients (47 on anti‐CD20, 10 on fingolimod, 33 on natalizumab, dimethylfumarate or teriflunomide), anti‐SARS‐CoV‐2 receptor binding domain (RBD) immunoglobulin G antibodies were quantified and their neutralization capacity was evaluated by enzyme‐linked immunosorbent assay (GenScript) and a virus neutralization test against B.1 historical strain, Delta and Omicron variants, before and after three to four BNT162b2 injections. Results After the primary vaccination scheme, the anti‐RBD positivity rate was strongly decreased in patients on anti‐CD20 (28% [15%; 44%] after two shots, 45% [29%; 62%] after three shots) and fingolimod (50% [16%; 84%]) compared to other treatments (100% [90%; 100%]). Neutralization activity was also decreased in patients on anti‐CD20 and fingolimod, and notably low for the Omicron variant in all patients (0%–22%). Delayed booster vaccination was performed in 54 patients, leading to a mild increase of anti‐RBD seropositivity in patients on anti‐CD20 although it was still lower compared to other treatments (65% [43%; 84%] vs. 100% [87%; 100%] respectively). After a booster, Omicron neutralization activity remained low on anti‐CD20 and fingolimod treated patients but was strongly increased in patients on other treatments (91% [72%; 99%]). Discussion In MS patients on anti‐CD20, an enhanced primary vaccination scheme moderately increased anti‐RBD seropositivity and anti‐RBD antibody titre, but neutralization activity remained modest even after a fourth booster injection. Trial registration information COVIVAC‐ID, NCT04844489, first patient included on 20 April 2021.

Longitudinal study of immunity to SARS-CoV2 in Ocrelizumab-treated multiple sclerosis patients up to 2 years after COVID-19 vaccination

“…The lack of nAbs increase after booster is consistent with one prior study using live virus assay in which “neutralizing activity against tested SARS-CoV-2 variants remained low or undetectable” after third or fourth booster doses in aCD20-treated MS patients. 22 An important novel finding of our study is that binding antibody levels remain stably elevated for up to 12 months after booster.…”

“…These results are comparable with the French report in which 9% of B-cell repleted MS patients reached the minimum threshold of antibody considered as ‘adequate protection’ by local health authorities. 22 Neutralizing antibody titers against Wuhan in healthy subjects were 3.13 +/- 0.41. Among uninfected VIOLA participants, Wuhan nAbs were 1.42 +/-0.71.…”

“…Even so, the antibody levels in our patients were much lower than in the reference healthy subjects, and a minority of VIOLA participants did not develop any post-vaccine antibody responses, in line with prior studies. 11,19,[22][23][24][25][26][27] Binding and neutralizing antibody levels decayed over time but remained elevated above the pre-vaccine level up to 12 months following the primary vaccine. This is similar to what has been observed for the general population: anti-Spike antibody responses peak around 21-28 days after the second vaccine dose and then decline, 28 presumably due to a decline in short-lived plasmablasts.…”

COVID-19 outcomes in patients with multiple sclerosis: Understanding changes from 2020 to 2022

“…7 pwMS can present lower immune responses to vaccination, 8 particularly with anti-CD20 and fingolimod. 9,10…”

“…7 pwMS can present lower immune responses to vaccination, 8 particularly with anti-CD20 and fingolimod. 9,10 However, most epidemiological studies investigating COVID-19 severity in pwMS are based on data from the first waves of the pandemic in 2020 or early 2021. 6,[11][12][13][14][15][16][17] The emergence of new SARS-CoV-2 variants of varying severity, 18 the development of vaccines with efficacy against symptomatic infections, 19,20 and the subsequent massive vaccination campaigns launched in 2021 to stop the pandemic have changed the epidemiology, risk factors, and outcomes for COVID-19.…”