Seroconversion following COVID-19 vaccination: can we optimize protective response in CD20-treated individuals?

Abstract

Although there is an ever-increasing number of disease-modifying treatments for relapsing multiple sclerosis (MS), few appear to influence COVID-19 severity. There is concern about the use of anti-CD20-depleting monoclonal antibodies, due to the apparent increased risk of severe disease following SARS-CoV-2 infection and inhibition of protective anti-COVID-19 vaccine responses. These antibodies are given as maintenance infusions/injections and cause persistent depletion of CD20+ B cells, notably memory B cell populations that may be instrumental in the control of relapsing MS. However, they also continuously deplete immature and mature/naïve B cells that form the precursors for infection-protective antibody responses, thus blunting vaccine responses. Seroconversion and maintained SARS-CoV-2 neutralizing antibody levels provide protection from COVID-19. However, it is evident that poor-seroconversion occurs in the majority of individuals following initial and booster COVID-19 vaccinations, based on standard 6-monthly dosing intervals. Seroconversion may be optimized in the anti-CD20-treated population by vaccinating prior to treatment-onset or using extended/delayed interval dosing (3-6 month extension to dosing interval) in those established on therapy, with B cell monitoring until (1-3%) B cell repopulation occurs prior to vaccination. Some people will take more than a year to replete and therefore protection may depend on either the vaccine-induced T cell responses that typically occur or may require prophylactic, or rapid post-infection therapeutic, antibody or small molecule anti-viral treatment to optimise protection against COVID-19. Further studies are warranted to demonstrate the safety and efficacy of such approaches and whether or not immunity wanes prematurely as has been observed in the other populations.

Long-term immunological consequences of anti-CD20 therapies on humoral responses to COVID-19 vaccines in multiple sclerosis: an observational study

“…In line with previous reports, we found a complete depletion of B cells at 6 months from anti-CD20 infusions and a stepwise approach toward the LLN within 18 months from last dosing. 20 Our real-life data corroborate findings from ocrelizumab phase II trials, showing a repopulation to the LLN by 72 weeks. 21 We observed a heterogeneity regarding B-cell recovery rates, ranging from repopulation to LLN within 1 year to incomplete recovery 36 months from the last anti-CD20 administration.…”

“… 14 A retained humoral vaccine efficacy despite complete peripheral B-cell depletion underpins the concept that generation of pathogen-specific antibodies occurs within the lymphoid tissues. 20 Together, these considerations argue against the hypothesis that vaccine efficacy strongly relates to the degree of B-cell repopulation. 20 Peripheral B-cell counts therefore appear not to be an appropriate biomarker to predict seroconversion rates in pwMS treated with anti-CD20 therapies.…”

“… 20 Together, these considerations argue against the hypothesis that vaccine efficacy strongly relates to the degree of B-cell repopulation. 20 Peripheral B-cell counts therefore appear not to be an appropriate biomarker to predict seroconversion rates in pwMS treated with anti-CD20 therapies.…”

Implementing education: Personal communication with a healthcare professional is a critical step to address vaccine hesitancy for people with multiple sclerosis

“…Our results suggest that personalised counselling is needed and should focus on those who are on DMTs, especially ocrelizumab and fingolimod, who are at greater relative risk for COVID-19 infection without appropriate timing ( Garjani et al, 2022 ). For PwMS on a B-cell-depleting DMT, where an adequate humoral response to COVID-19 vaccination requires a delay in DMT administration, fears surrounding possible disease relapse must be assuaged and relative risk with respect to increased complications with COVID-19 infection should be addressed in a personalised manner by the MS clinician ( Huang et al, 2021 , Baker et al, 2021 , Karussis et al, 2021 ).…”

How important are COVID-19 vaccine responses in patients with MS on disease-modifying therapies?

“…The Omicron strain and the likelihood of future immune escape variants challenge the widespread and rapidly adopted dogma to delay the introduction and/or further of ocrelizumab ( Baker et al, 2021 ) and fingolimod (personal communication Prof. Anat Achiron, Tel-Aviv University, Israel). The object of the latter is to permit sufficient peripheral B-cell reconstitution to facilitate an antibody response to the vaccine(s).…”