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 coronavirus disease 2019 (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 severe acute respiratory syndrome corona virus two (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 antiviral treatment to optimize 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.

Keywords: CD20 B cells; COVID-19 vaccination; autoimmunity; immunotherapy; multiple sclerosis.

Graphical Abstract

Figure 1:

B-cell lineage and CD20-specific antibodies. A simplified schematic of the B-cell lineage related to CD20 antigen expression and the CD20-specific antibodies. Epstein–Barr virus (EBV) can generate memory B cells in the potential absence of antigen and co-stimulation or they can be antigen expanded.

Figure 2:

Deletion and repopulation of B cells following ocrelizumab infusion in MS. Individuals received 600 mg ocrelizumab Q24W for four cycles or placebo followed by three 600 mg ocrelizumab cycles [6]. The raw data were extracted from the phase II ocrelizumab extension study supplied via the www.vivli.org portal using R software. The results represent the mean ± standard deviation; n = maximum 46–47/group.

Figure 3:

CD19 B-cell repletion after repeated ocrelizumab infusions. Individuals received 600 mg ocrelizumab Q24W for three or four cycles followed an 18-month treatment-free period [6]. The data were extracted the raw data from the phase II ocrelizumab extension study (NCT00676715) supplied via the Vivli Inc. portal using R software. Data were stratified according to baseline body mass index. The results represent the approximate time from the last infusion and probability of repopulating to 1% CD19 B lymphocytes.