The Trickle begins..waiting for the Flood! Blunted vaccine responses and CD20-depleting antibodies

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The case reports are starting to arrive

“We present a patient with MS on ocrelizumab, who received the Pfizer mRNA COVID-19 vaccine, and did not seroconvert 27 days after the second vaccine dose as measured by an FDA approved Anti-SARS-CoV-2 S assay”.

He received his first dose of SARS-CoV-2 (Pfizer) vaccine 5 months after ocrelizumab infusion, followed by the second dose 21 days later. There was a moderate post-vaccination systemic reaction with myalgias and fatigue. The person received another ocrelizumab infusion 9 days after the second dose of the vaccine. This is because in other studies it has been shown that maximal antibody responses can be detected within 7 days of the second vaccination. At the time of infusion he tested negative for antibodies to the SARS-CoV-2 nucleoplasmid antigen so had no seemingly been naturally infected.

So this is ominus as the vaccination was used at times to give the best opportunity to give a response within a six monthly dosing cycle and there was none. So now the question is can we find a condition that allows seroconversion because the writing is on the wall given the information that has come out of Israel and so most people will not seroconvert. So next question is will be , is there a T cell response? Likewise if your CD19 B cells start to recover can you make an antibody response. About 5 % of people have recovered their cells before 6 months or will you need to wait a little bit to convert. Most people in UK will have been offered their jab before we get sufficient insight, but there are other parts of the World yet to get a vaccine and importantly there may be boosters to deal with.

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MouseDoctor

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  • I went through HSCT for MS 15 years ago. I just had my covid19 from phizer. So are stating phizer and moderna will make T spike make people with MS speed up. I’m 15 years free of MS actually almost 16 years. So are you trying to come up with some kinda of covid19 that safe for MS patients?

    Thank You

    Michelle

    • If you had HSCT 15 years ago, your response is likely to be no different from any other person and so the vaccine should work. The COVID19 vaccines are relatively safe for people including those with MS, what we been to do is work out if there is an optimal way to allow this to happen with some therapies within a short time after treatment. Forr most agents this will not be a problem. There is a way to creat this protection using long lives antibodies this is under testing at present

      • Thank you so much for your response! I like that your working on something to help people with MS. This has been hard on everyone but I think how hard is on MS patients. Thank you for letting me know.

        Thank you so much for helping MS patients!

        Michelle

      • Just curious – who is working on extended half life anti-Covid antibodies as a prophylactic treatment?

      • Just curious – who is working on extended half life anti-Covid antibodies as a prophylactic treatment?

        • May be OK, we know with rituximab there is bunting of the response 6-12 months, but if B cells have returned there is a possibility of success

          • Thanks, I’m sure the extended dosing schedule may not have helped, but I will go for part two on Friday and hopefully some immunity will stick

  • I heard of people on Anti-CD20 mounting a strong antibody immune response with a CD19 count around 30-50 cells/mcl. Clearly not on a regular dosing schedule but based on repopulation. Maybe it is worth waiting for partial repopulation as new B cells are naive and not memory. But this is nothing new under the sun just a few numbers more 🙂
    In the centre I am treated several patients delayed their ocrelizumab dose so in a few months I think some data may surface.

    • Maybe this trickle will become the answer…You are correct some people delayed lets hope if gives a good answer

      • I had my first jab of Pfizer at week 34 post Ocrelizumab infusion.

        At week 38 cd20 was 0.054 and 2 hours later I received my second Pfizer jab.

        At week 41 so 3 weeks after my second Pfizer jab I got my new Ocrelizumab.

        My neurologist and I decided that meds should be customized, so at week 26 of each cycle we do bloodtests. We do that every 4 weeks until the cd20 count is at new infusion level. This is why I don’t have a 26 wk cycle.

        All other meds are customized, why not these heavy ones???

        • I have similar arrangement with my neuro. Except this time round when the vaccine was arriving we decided to skip one of the monitoring rounds figuring now we have to wait anyhow

          • Dear Prof G.

            What’s your opinion on customizing meds?

            Thanks and regards
            Rogier

          • I am curious if you are outside of the US? I am unable to find a neuro who is willing to do this for Ocrevus and wondered if neuros elsewhere were more open to it, especially in places that have different litigation + private insurance dynamics.

        • Are you outside of the US? I am unable to find a neuro who is willing to do this for Ocrevus and wondered if neuros elsewhere were more open to it.

  • Thank you so much for your response! I like that your working on something to help people with MS. This has been hard on everyone but I think how hard is on MS patients. Thank you for letting me know.

    Thank you so much for helping MS patients!

    Michelle

  • I’m on Ocrelizumab and 2 days after my 2nd Pfizer jab, I was unable to get out of bed. If I haven’t seroconverted, another response definitely occurred. I don’t particularly want to know about B cell response, because we know that will be blunted by anti-CD20. These studies are predictable and need to be done, to prove that the obvious is happening, but I want to see studies which will hopefully show me that I didn’t go though the unpleasant few days for nothing.

    • Reactogenicity (feeling crappy after the JAb) and antibody levels I dont think correlate. Sadly negative stories sells column inches

  • Would you expect additional vaccine doses to improve the chance of a response, e.g. 3+ doses of Pfizer/Moderns, or 2+ J&J? Or doesn’t it work that way?

  • If most of the rest of the population is vaccinated,
    then patients on anti-CD20 will be protected even if they don’t build any personal protection in response to the vaccine.
    Meaning, their safety will depend on everyone else getting vaccinated, not on getting the vaccine themselves.
    Is this logic sound?

  • If he felt lousy post vaccine wouldn’t that mean there was some reaction at least? Hoping at least some t cell antibodies are there.

  • When the vaccine was offered to me (Pfizer 1st dose), I took it although I was only 8 weeks post Rituxan infusion (been on it since 2009). It didn’t seem like waiting for months and months would make much difference to vaccine response. I should be receiving the 2nd Pfizer dose next week. I really wish that I could be part of a study measuring antibody response post-vaccination. I answered a survey to volunteer for research at Johns Hopkins on this very subject. Hoping they want my blood to test. We need to know more about how this is going to play out for people on B-cell depleting therapies.

  • On RTX for 6+ years, Moderna vax, no spike IgG antibodies after first or second dose. Fascinatingly came back positive on T cell test, which analyzes TCRβ sequences and puts them into a machine learning model trained on historically COVID-positive patients. Not sure if this means I just had asymptomatic disease in the past or if the vaccine did something, but cool data point either way that there’s something going on with the T cell repertoire, even in someone who’s been on anti-CD20 therapy for a while and who does not produce antibodies.

  • Thanks for this. Is there any info on people on anti CD20 who HAVE mounted an antibody response?

    • Yes there are in the Israeli data set there was 20% we hope that when it arrives there will be indication of when the positives occurred

  • OK, here is my contribution to MS medical science (here in the US) for what it’s worth: I had only two half doses of O. I am probably (but not certainly) SPMS, no MRI evidence since 2001, diagnosed 1990, on Betaseron 1995 to O infusion. Pain in R calf 2+ yrs. but not sure the extent to which flat foot accounts for pain. EDSS + or – 5.5.

    3rd full dose of O was due March, 2020. Headlines coming out of Europe. MS doc on “leave”. His nurse saying covid no big deal here and to go ahead, no reason to believe you can’t fight infection. Weighing the options on my own (including “NEDA”), I decided no infusion (news out of Europe was quite bad).

    Thought I had a weird infection of throat & low fever in April ’20 (for 8 days). Got tested for antibodies around July: negative result. MS doc stopped treatments with O for new patients. Others stuck “between a rock and a hard place”, damned if you do, damned if you don’t. My immune function as assessed by blood work about normal. (I am preparing to head back out into the world of maskless idiots in Lancaster PA, and want to know my status). Was fully vaccinated (Moderna) by March 2021. 20 days later, antibody test is positive. Yea! (At least something is going right).

    No info on which antibody tests were used, Wellspan was unable or unwilling to disclose.

    Unfortunately (in my opinion), O blogs are discouraged any informed news or opinion other than what NMSS says. O is currently advertising on TV “full steam ahead”. Many people aren’t aware or don’t want to be, concerning O infection and vaccination difficulties. They believe “timing” is the fix.

    That’s my story.

      • Because of “my nature”, I just find it fascinating watching people’s behavior in response to difficult situations. “What are the motivating factors?”, I am always speculating on. I watch the blogs and notice the chatter about O, covid infection and vaccine response. There is not always well-informed attitudes or information circulating. Some are well informed, others are not. On the O blog here in US, “timing”, as I said, is the “big fix”, along with T-cells. The mantra is repeated enough to make it sound as fact. When you time it, and your T-cells are right, you will have no problem. It is not stated as a question, but rather the answer which has been proven.

        When the “take off your mask” proclamation comes from the CDC, which is right around the corner here in The US, no one will know who is vaxxed or not vaxxed. Disease may spread amongst the unvaxxed. New variants will continue to be born. Will the O people wear a mask? Seems at present, like that would be the wise course of action. But not if they believe that they “timed it right” and their T-cells are good, just like their doctor and the NMSS told them. Who wants to stand out as “sickly” and wear a mask, especially when they’ve been told they are not at risk and essentially in the same boat as those who are vaxxed? So it is fascinating for me to watch the data trickle, or flood in, as you put it.

        • Here is an example of exactly what I am talking about, less than 24 hrs ago, (Facebook):

          “Ocrevus does not eliminate all of one’s B cells. Please read your literature again. And it was quite refreshing to me to not have any reaction to my Moderna second dose. I expected one; but nothing. And now I feel happy that I can travel to see family safely for me and for them. My doc suggested I wait until 4 months post Ocrevus; and yes, I only waited 3. But I feel quite confident about my Ocrevus, my health and taking care of my MS the best way I can. I don’t like having MS; but as the commercials say. I have MS but it doesn’t have me!”

          • And the “freak out” apparently has begun- (again, very recent from Facebook)

            “Oh, I really do hope that everyone has antibodies! I had seen some people saying that antibodies may not show up? And that it’s possible to have a negative result but still have some protection? I have no clue if that is accurate/true, but I hope so (for those who have tested negative)!”

            “How does it feel going through life being condescending with people you don’t know because they are asking about the effectiveness of a new vaccine that they didn’t test on millions of people on Ocrevus? I literally read posts of people saying their neurologists don’t know. So clearly there are ignorant people who ARE professionals.”

            {past test results are meaningless] “standard antibody tests will be negative, they need to test for the Covid spike protein, it’s a new test and only recently starting to become commercially available”

            “I had an immune response so that is a good sign. By immune response I mean I was sick for about 36 hours after vaccination. Hopefully that means protection from covid for at least a little chunk of time.”

            “You don’t have the data for vaccines and ocrevus so you’re just assuming there’s none?
            No. There are millions of pieces of information that you don’t have, will never have, won’t understand, and don’t deserve.”

            “absolutely it is it’s something that I have also questioned myself. I won’t see my neurologist until June. Hopefully I have antibodies.”

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