COVID19..Drip, Drip Drip….B cell repopulation determines the ability to give antibody response after COVID-19 vaccination


Learning from other conditions is useful. As there are more people with rheumatoid arthritis than MS we will see alot of anti-CD20 papers with rituximab. There will be subtle differences compared to ocrelizumab. So when you read the paper that says the vaccine response to anti-CD20 is unknown….it’s not its getting less unknown by the day. If you are taking ocrelizumab you should expect to be making protective T cells even whne you antibody response is inhibited

Look into my crystal ball to see the future for MS:-)

Mrak D et al. SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity.Ann Rheum Dis. 2021 Jul : annrheumdis-2021-220781.Published online 2021 Jul 19. doi: 10.1136/annrheumdis-2021-220781PMCID: PMC8295012PMID: 34285048

Objectives: Evidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a humoral and T-cell-mediated immune response against SARS-CoV-2 after immunisation.

Methods: Patients under RTX treatment (n=74) were vaccinated twice with either mRNA-1273 (Moderna) or BNT162b2 (Pfizer). Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S (Roche) immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests. SARS-CoV-2-specific T-cell responses were quantified by IFN-γ enzyme-linked immunosorbent spot assays. Prepandemic healthy individuals (n=5), as well as healthy individuals (n=10) vaccinated with BNT162b2, served as controls.

Results: All healthy controls developed antibodies against the SARS-CoV-2 RBD of the spike protein, but only 39% of the patients under RTX treatment seroconverted. Antibodies against SARS-CoV-2 RBD significantly correlated with neutralising antibodies (τ=0.74, p<0.001). Patients without detectable CD19+ peripheral B cells (n=36) did not develop specific antibodies, except for one patient. Circulating B cells correlated with the levels of antibodies (τ=0.4, p<0.001). However, even patients with a low number of B cells (<1%) mounted detectable SARS-CoV-2-specific antibody responses. SARS-CoV-2-specific T cells were detected in 58% of the patients, independent of a humoral immune response.

Conclusions: The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in RTX-treated patients, once peripheral B cells at least partially repopulate. Moreover, SARS-CoV-2-specific T cells that evolved in more than half of the vaccinated patients may exert protective effects independent of humoral immune responses.

(A) Get vaccinated make an antibody response, (B) have B cells make an antibody response, (C&D) the more B cells the more likely you have an antibody response….(D) there are a few exceptions. Here have 3% B cells compared to lymphocytes and you make some form of an antibody response.

Most people also make a T cell response

No this is not a drawing of a train. Pos =positive = a control it should work. Neg = megative is shouldnt work, S1 is T cell response against Spike S1 region, S2 against S2 region of Spike. S1 has the receptor binding domain the circles at the bottom are called Elispots the more dots (the more of a response

Yes you are getting fed up seeing the same result over an over again. However it will be that you eventuallly believe this. Most neurologists are not looking at the arthrtitis literature and so it will take longer for the MS data to emerge….but emerge it eventually will.

So the water torture, drip drip drip is for them. So I am giving you MDs crystal ball to allow you to look into the fututre. Now I must say the kinetics may be different as the B cells will return slower with ocrelizumab than rituximab and so it will be harder to see. Most but not all people make anti-T cell response just like healthy people.

The big question is going to be will we try to exploit this information when boosters come or say thanks very much its good to know. I suspect the latter.

However if we plough on we should test to see what may happen when we boost before it it is nationally rolled out.

Would you prefer to be optimized to give the best response you can?

COI: multiple but not relevant

Disclaimer: Please note that the opinions expressed here are those of the author and do not reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust or Queen Mary Univeristy of London.

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  • Nice work

    You say ;:once an immune response immune response for life

    So why do we really need boosters?

    For example, one study found
    IgG1+ memory B cells specific for the 1918 pandemic
    strain of influenza virus circulating in the blood of survivors
    90 years after primary exposure to the virus


    Thus, these studies reveal that survivors of the 1918 influenza pandemic possess highly functional, virus-neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure – well into the tenth decade of life.

    Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors

    On the other side bad new for auto immune diseases 🙂

    • Good point it is probably immunity for life, but the boosters will keep the antibody response high and help with sterilizing immunity to stop spread

  • Hi MD! Have you seen any studies that map out how long it takes patients to repopulate B-cells? I suspect it’s driven in part by how long they’ve been on an aCD20 (ie, total # of doses). I suspect this exists, but my Google sleuthing to find it is failing me.

    • Most people who ge ocrelizumab get it every 6 months for life and so the data of what happens when you stop is rather rare. There were about 150 people from the phase II study that had the 600mg dose for 3 or 4 doses and then nothing for 18 months.

      Yes we have two papers that Baker et al published last year MSARDS/CEI (Search Baker Schmierer, Ocrelizumab and 2020 you will find them. For the memory B cells for most people it will be longer than 18 months (this will help keep MS at bay). To get to lower level of normal gor CD19 takes 62 weeks on average after 3 doses and 72 weeks on average after 4 doses (range 5.5 months to 3.25 years). So if you wanted to stop ocrelizumab to wait for B cells to return it says you may have to wait a long time and hope the MS does not return in this time. However past a 3 month wait there is little data to know the safety.

      At the moment I have access to the data but I can’t sort it as I dont know how to use the statisitical package. When you ask for the data they make you sign an agreement that you will only look at what you ask to look at and that you show them what you have done. They dont tell you what data they have when you ask the question (it would be better to see what is available first before you ask question). They dont give you what you ask for but they give you everything e.g. in thirty spread sheets. These may have 100 or more columns and 2 millions rows and within each column you may have the information from 150 different tests over two years. They dont tell you where the information you ask for is or what the columns mean and you have to work in a virtual world with gate keepers who stop you removing the data so you can work on it offline with packages you know. In one examplple there are 800 individuals in a spread sheet. However imagine every test (there are often over 150 per person) that they can do on each individual over say 2 years every month. Too much information to copy and paste into s pread sheet I could work with

      I was going to get it last week before our statisticians had to go to hopsital and so have to wait until they get back from holiday. However to get to 1% may be quicker than the time abouve, what I plan to do is work out how many people get to 1%, 2%, 3% at 6 12 18 months. However I have to submit the data to Roche for 30 days before I can post it

  • Ocrevus patient here. I got a j and j “booster” 5 months post infusion despite having had two Pfizer doses months beforehand. Still zero antibodies.
    Obviously n of 1 but a real world example.

    • Thanks for your insight….Funny in US people having had the J& J are flocking to get booster with RNA vaccine….I think your experience is biology if you have no B cells you are not going to make antibodies no matter how many boosters.

  • What would be nice to know is to what extent the T cell only response confers reliable protection.

    If a healthy control who has developed the expected level of vaccine response is a notional 100% then compared to that what percentage of protection is afforded by a T cell only response?

    Is there any work that gives an insight into the comparative level of protection?

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