Ofatumumab and COVID


Faissner S, Heitmann N, Plaza-Sirvent C, Trendelenburg P, Ceylan U, Motte J, Bessen C, Urlaub D, Watzl C, Overheu O, Reinacher-Schick A, Hellwig K, Pfaender S, Schmitz I, Gold R. Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination. Front Immunol. 2022 Aug 31;13:980526. 

Objective: The pandemic induced by SARS-CoV-2 has huge implications for patients with immunosuppression that is caused by disorders or specific treatments. Especially approaches targeting B cells via anti-CD20 therapy are associated with impaired humoral immune response but sustained cellular immunity. Ofatumumab is a human anti-CD20 directed antibody applied in low dosages subcutaneously, recently licensed for Multiple Sclerosis (MS). Effects of early ofatumumab treatment on alterations of immune cell composition and immune response towards SARS-CoV-2 are incompletely understood.

Methods: We here investigated immune cell alterations in early ofatumumab (Ofa) treated patients and effects on humoral (titer, neutralization capacity against wild type, Delta and Omicron) and cellular immune responses in Ofa treated MS patients following a third vaccination against SARS-CoV-2 compared to healthy controls.

Results: We show that a mean treatment duration of three months in the Ofa group led to near complete B cell depletion in line with altered composition of certain CD4+ T cell subpopulations such as enhanced frequencies of naive and a decrease of non-suppressive regulatory T cells (Tregs). Titer and neutralization capacity against SARS-CoV-2 variants was impaired while cellular immune response was sustained, characterized by a strong T helper 1 profile (Th1).

Interpretation: In summary, low dosage ofatumumab treatment elicits sustained depletion of B cells in line with alterations of immune cells, mainly Tregs. This is associated with impaired humoral immune response towards SARS-CoV-2 vaccination but preserved, Th1 driven cellular immunity adding crucial information regarding early effects of low dosage anti-CD20 therapy on humoral and cellular immunity.

So in this study antibody response to SARS-Cov-2 disappears but T cell response is not inhibited. This is fine it is not different from rituximab or ocrelizumab so we can safely suggest this is an anti-CD20 mediated effect. New antibody responses come from naive B cells and as ofatumumab inhibits these cells it stops the formation of antibody producing cells. These naive B cells can produce memory B cells which have the potential to make vaccine responses in the future. Alternatively naive B cells can make plasmablasts that can make antibody producing cells. These latter cells may not be susceptible to the effects of ofatumumab and may or may not require memory B cells. This explains the COVID-19 vaccine response.

Now you say how is this inhibiting MS? I will say it is inhibiting the activity of pathogenic memory B cell, but not the T cell response. However other people want to think that ocrelizumab works because it inhibits T cells. Others may infer that it increases T regulatory cells maybe OK for treatment MS but what about vaccine reponse. However, how can that be? Not inhibitng T cells in COVID-19 vaccine responses but inhibiting the MS T cell response…Can you have it both ways? Either the CD20 T cell depletion significance is a load of old tosh or it is doing something biologically different. Maybe it is how T cells are activated and MS needs antigen presenting B cells and vaccine responses does not.

CoI None

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