The First Report of a Blunted vaccine response to Ocrelizumab, three months after the other first reports.


So in the race to get there quickly, we are seeing the case reports surface of people on ocrelizumab, not developing an antibody response. Below, we see a paper of 4 people…and they report “the first data“..which as ever is never the first data….They say the response is blunted…then say “data are urgently needed to confirm and expand these preliminary results”…but the data were published well over two months ago and reported over three months ago in over ten times more people before the first report was submitted. We have seen another 40+ more (Karussis) and their are others including our own.

However, in this report people did make a response (above 33 antibody units was considered positive). Indeed 2/4 people did, but the response wasn’t a strong response. But it was a response. At 2 weeks after the first does the level was about 200 antibody units in health care workers, which is when there is high protection from the vaccine and 2000 antibody units after the second dose. Because the vaiants of concern often require more antibody to neutralize this the higher levels the better. One person with MS made 175 antibody units after the second dose and had delayed infusion and got their vaccine after about 6 months and they also had detectable B cells in the blood. These people are the gold dust that will tell us what to do…..

It seems that the French approach favoured by some is going to give immunosuppressed people a third dose of vaccine. “The patients who are eligible for the third dose will receive either the Pfizer-BioNTech or Moderna vaccine. They should receive the third dose four weeks after the second, or as soon as possible if it has already been more than four weeks since their second dose.  I am not calling the shots, but the Moderna Vaccine gives higher antibody levels than Pfizer and one has to ask is this good after bad without learning. It may give a T cell boost but if you want T cells then maybe you want them to target other targets in addition to Spike such as nucleocapsid…but the approved vaccines in West are all against Spike. Would it be worth waiting until B cells are recovering? But in effect it adds at least another month on the process, but the data show that waiting up to 5 months to start vaccine still results in lack of seroconversion in many people. If we can collate all the data a pattern hopefully will emerge and hopefully people will present the data so that it can be collated.. I think I can see something already emerging when looking across condidtions, but it is better to be informed than guess. In the UK if we have a third dose what will it be?

I don’t know, but I expect we will all get one in due course.

Preliminary evidence of blunted humoral response to SARSCoV2 mRNA vaccine in multiple sclerosis patients treated with ocrelizumab.Gallo A, Capuano R, Donnarumma G, Bisecco A, Grimaldi E, Conte M, d’Ambrosio A, Coppola N, Galdiero M, Tedeschi G.Neurol Sci. 2021 Jun 15. doi: 10.1007/s10072-021-05397-7

Objectives: Several concerns regard the immunogenicity of SARS-CoV-2 vaccines in people with multiple sclerosis (pwMS), since the majority of them is treated with immunomodulating/immunosuppressive disease modifying therapies. Here we report the first data on the humoral response to mRNA SARS-CoV-2 vaccine in a case series of 4 pwMS treated with ocrelizumab (OCR) as compared to a group of healthy subjects (HS).

Methods: We collected serum samples at 0, 14, 21 days after the first dose and 7 days after the second dose of BNT162b2-mRNA-Covid-19 vaccine from 55 health-care workers and 4 relapsing pwMS on OCR, with no history of Covid-19 infection. Sera were tested using the LIAISON®SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.) for the detection of IgG antibodies to SARS-CoV-2 spike protein. The anti-spike IgG titers were expressed in Binding Antibody Units (BAU), an international standard unit.

Results: At baseline all subjects were negative for anti-spike IgG. Seven days after the second dose of vaccine all HS mounted a significant humoral response (geometric mean 2010.4 BAU/mL C.I. 95% 1512.7-2672) while the 4 pwMS showed a lower response (range <4.81-175 BAU/mL).

Discussion: Humoral response to BNT162b2-mRNA-vaccine in pwMS treated with OCR was clearly blunted. Further data are urgently needed to confirm and expand these preliminary results and to develop strategies to optimize the response to SARSCoV-2 vaccines in pwMS on OCR.

However if you do not make a B cell response can you be given one.

STORM Chaser is a just failed trial, which suggests you can. As you know you have to give an outcome and the trial failed to meet its endpoint. This has happened with many antibodies. They looked at people with recent contact with infected people and asked if you give people a neutralizing antibody cocktail do you stop symptomatic infection. The answer was it wasnt good enough, but do it in people how do not have an activie infection and have been infection free for a week and the answer is 92% protection. Luckily they have other trials to try and see if this is the case.

Here are the results. Seems companies are learning that they dont need academics to publish their work

AZD7442 is a combination of two LAABs – tixagevimab (AZD8895) and cilgavimab (AZD1061) – derived from B cells donated by convalescent patients after SARS-CoV-2 virus, the human monoclonal antibodies bind to distinct sites on the SARS-CoV-2 spike protein and were optimised by AstraZeneca with half-life extension and reduced Fc receptor binding. The half-life extension approximately triples the durability of its action compared to conventional antibodies and could afford six to 12 months of protection from COVID-19 following a single administration.

So there you go anti-CD20 and AZD7442…P.S. Im not a

Coi multiple byt none relevant

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

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  • In Belgium, some neurologists are testing antibody response (IgG) prior to vaccination, and then 2 and 6 months after first dose (or thereabouts) in their MS-patients, with all DMTs.
    Good practice?

    • you’d think so wouldn’t you? Otherwise how is anyone ever going to know if we have had a response to the vaccine? When we are lying in the ITU after catching covid?

    • It is good to know baseline because then you can see a change but if they measure at 2 months and not one month they may get a shock. I have see people poisitive at 4 weeks after first dose, negative at 6 weeks, likewise the response after the first dose is pretty weak or non existant, the key is what happens after the second dose.

      • I think the weak response after the first dose is the reason why they test at 2 months (most vaccinations here are Pfizer, so you should have had 2 doses by then)

  • I’ve been considering taking a third dose after reading a case report (n=1) of a an immunosuppressed transplant surgeon who made antibodies after a third dose, but not with two doses.

    I am however in Canada where the focus is getting people their first shot, so I haven’t even had my second dose yet.

    To make my initial consideration even more meaningless, the bloodwork for my next Ocrevus infusion just came back and I am below the minimum threshold for IGg, IGm, and IGa. Ocrevus has provided me with some much needed stability, but alas, it looks like the price of that stability may be higher than it was worth.

    I suppose there is still some hope for the AZ cocktail, for me, and for my education!

    • It perhaps depends on the immunosuppressive, but my take is this if there are no B cells this month and no B cells next month will it make a difference? Yes I know that whats in the blood is not the same as that in the lymph gland but I think we want to try and use the available data to optimise once people have had their first rounds. I made essentially no respose after the first dose.

      • MD, how long does it usually take for B cells to repopulate? I realize it probably varies but is there a general sense? 6 months after Ocrevus and basically nothing. Strong consideration to wait for repopulation, and then get another jab. Thought I read that it could be 3 years….hope I am wrong.

        • On average 60-70 weeks but it very variable from about 5.5 months to over 3 years. That is back to lower limit of normal you probably need less cells than that

          • I trust the answer is not so simple-nothing in immunology ever is-but if anti-cd 20 DMT removes B cells potentially up to more than 3 years, why is it administered roughly every 6 months? Isn’t it more economical to test level of one’s B cells and if beginning to repopulate then you go for another infusion?

          • Good question….it is administered every 6 months because that is what the label says… would be logical to see if you are a quick or slow repopulator and dose in an intelligent way….my one proviso is that we need to check that this delay does not cause persistent anti-drug antibodies

          • 5’7” 130 pounds and four cycles of OCR……started to repopulate at month 9 and experienced rapid subsequent increases during month 10 and 11. Stayers to use TERI (month 9) to modulate repopulation and keep CD-19 below baseline. Which did work!

            Warning: Experienced mild relapse in month 10.

        • 5’7″ 130 pounds, 4 cycles of OCR. Started to repopulate at 9 months post infusion. Experienced rapid increases in months 10 and 11. Used TERI to modulate CD-19 repopulation in order to keep them below base line, which was an effective strategy. At month 12, my CD-19 b cells stabilized around 55 ul, which was 25ul below base line.

          WARNING: I had a mild relapse at in month 10, so proceed with caution.

          • Thank you for your insight and experience. What was your motivation for going off Ocrevus? Was it anticipation that vaccine efficacy would be blunted as predicted by Prof. G?

      • Mousedoctor, thank you. I say to noone In particular but to all who think vaccination is useless as well as decision makers who like to slow walk decisions: Because of current CDC recommendations I can’t get any of my top notch doctors at top notch places to order an antibody test. Some reputable and some fly by night labs will take my money for antibody test but none will state the type of antibody test I’m ordering and all add CDC disclaimer it’s not for vaccinated to determine antibody response. So I assume based on my anti cd20 therapy and timing of vaccine that I don’t have antibodies. Fear, primal fear, got me pondering whether I should just get a third vaccine. But it’s a guess. And I need more. I think. I’m so desperate to not be in fear. I self isolate. And slowly go stir crazy on this indefinite ——fest. My community is 33% vaccinated with R (t) factor over 1 for past two weeks. .My family enters and exits the outside world bringing germs home. I caught a bad non COVID-19 cold and feared I would die. I made my adult daughter memorize the phrase “give my mom monoclonal antibodies stat”, which are available here upon admission to icu, as well as Hydroxychloroquine. Ha. Both are compassionate use. But Compassion doesn’t seem to be the key to get people vaccinated here in US. And Psychologists say shaming the irresponsible won’t increase vaccination either. Why doesn’t self interest motivate? What has made the ignorant so powerful? Rhetorical rantings today after my neuro says no to 3rd vaccine, and hubby wants data, and I am too cowardly to jump on a guess.

        • Suebee, you are not alone with your frustration and fear. As an aside, I inquired of Regeneron about prophylaxis use of monoclonal amtibodies on a compassionate use basis and they unfortunately had no information to offer.
          But you are indeed correct that it is available in hospital settings if one has a positive covid dx, and is deemed high risk. With potentially a very long wait for B cell repopulation for those that were on anti cd20 such as Ocrevus, why in the world would something like monoclonal antibody cocktail not be offered? A large trial showed it worked. Maddening.

  • What about people who start Ocrevus after having both shots? Will whatever immunity that is generated be maintained?

    I assume that the issue will be with booster shots and new variants after treatment is started

    • If you start after both shots I expect you to have response levels identical to other people…I have seen this happen. The booster shots should boost whats there, the variants may be more difficult

  • Have been on Ocrevus since 2017. Had two Moderna shots. Had antibody test just under 6 weeks after shot no. 2 and did not form antibodies even though I had fever and chills after shot no. 2. As far as I know I have not had Covid.

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