Third Jab and lack of antibody response following anti-CD20 treatment. The same old.


During the COVID pandemic the mantra it seems has been “some immunity is better than no immunity” and so for people taking CD20 depleting antibodies being treated on a 6 monthly cycle the likely reality is that you have produced either no anti-SARS-CoV-2 antibodies or very low levels of anti-SARS-CoV-2 antibodies.

Therefore, on balance you are likely to have quite poor immunity against the omicron variant. So you will be at risk of catching the virus if you contact it. This is because high levels of antibodies are needed to offer some protection from becoming infected.

Therefore, you have to rely on the T cell and innate immune response to clear the virus or drugs.

I am sure some T cell response will be of value in many people.

To delay and hope for a B cell repsonse or boost away. That is the question.

I have to say I think we have probably missed the opportunity for the pharma companies to optimise vaccine responsiveness again and soon we will be doing vaccine round four and we will be too slow to do the pilots that can help inform the general roll-out to improve the value of the vaccinations.

However, we are now if a different place as there are some anti-virals that can assist people who do not make immune responses against the virus. There is still an anti-viral antibody that is active even against omicron and now there are anti-viral chemicals available in some countries.

The key to sucess is to recognise that you are infected and have symptoms. You can do this by testing and being aware of the symptoms and if you are positive and have risk factors for a bad time.

Getting access to the anti-virals as soon as possible is key to the successful use of anti-virals

In the USA, a drug has been approved and this is called paxlovid. This is a mixture of two drugs and one of them is called ritonovir. This blocks liver enzymes (CYP3A and CYP2D) that are responsible for breaking down drugs and so it means that the other drug in the combination will work for longer to kill off the virus. The down side is this liver enzyme also breaks down many therapeutic pills and so it means that they will work for longer. A concern could be that this could affect the side effect profile of some drugs.

Now, I would not be so worried, as it probably safer to save you with an anti-viral for a few days at he potential expence of not taking a pill to stop a non-life threatening situation, but what I would say is have a list of the different medications that you are taking and if you are unfortunate to get infected and have risk factors and when you talk to your doctor and health care team and you get offered paxlovid, remember to tell them what you are taking.

So drugs being used in MS studies have this potential so again I say not to worry and importantly chemical MS disease modyfying do not appear to be affected by these particular enzymes

Humoral Immune Response after the Third SARS-CoV-2 mRNA Vaccination in CD20 Depleted People with Multiple Sclerosis.Achtnichts L, Jakopp B, Oberle M, Nedeltchev K, Fux CA, Sellner J, Findling O.Vaccines (Basel). 2021 ;9(12):1470. doi: 10.3390/vaccines9121470.

CD20 depletion is a risk factor for unfavorable outcomes of COVID-19 in people with MS (pwMS). Evidence suggests that protective IgG response to mRNA-based vaccines in B cell-depleted individuals is limited. We studied the seroconversion after the third mRNA SARS-CoV-2 vaccine in B cell-depleted pwMS with limited or no IgG response after the standard immunization. Sixteen pwMS treated with ocrelizumab or rituximab received a third homologous SARS-CoV-2 mRNA vaccine, either the Moderna mRNA-1273 or Pfizer-BioNTech’s BNT162b2 vaccine. We quantified the response of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 four weeks later. An antibody titer of 100 AU/mL or more was considered clinically relevant. The median time between the last infusion of the anti-CD20 treatment and the third vaccination was 22.9 weeks (range 15.1-31.3). After the third vaccination, one out of 16 patients showed an IgG titer deemed clinically relevant. Only the seroconverted patient had measurable B-cell counts at the time of the third vaccination.

The development of a humoral immune response remains rare in pwMS on anti-CD20 therapy, even after third dose of the homologous SARS-CoV-2 mRNA vaccine. It remains to be determined whether T-cell responses can compensate for the lack of seroconversion and provide sufficient protection against CoV-2 infections.

More details of treatment responsiveness

Pitzalis M, Idda ML, Lodde V, Loizedda A, Lobina M, Zoledziewska M, Virdis F, Delogu G, Pirinu F, Marini MG, Mingoia M, Frau J, Lorefice L, Fronza M, Carmagnini D, Carta E, Orrù V, Uzzau S, Solla P, Loi F, Devoto M, Steri M, Fiorillo E, Floris M, Zarbo IR, Cocco E, Cucca F. Effect of Different Disease-Modifying Therapies on Humoral Response to BNT162b2 Vaccine in Sardinian Multiple Sclerosis Patients. Front Immunol. 2021 Dec 9;12:781843. doi: 10.3389/fimmu.2021.781843. 

About the author



  • I am on my second day of Lagevrio having only started in Day 4 (I was not able to source any during the Christmas weekend). Now how come the Phase 3 results are so poor when compared to phase 2?

  • What is the situation If you are vaccinated x3 times prior to starting ocrevus and made antibody response, I know immunity wanes with time but will there still be some immune memory retained as time passes, like there is with childhood vaccines?

  • Thank you for another helpful post, MD. I hope you are managing a decent holiday season despite the pandemic.

    I agree with you about Paxlovid. I’d like to add that I really hope pharma and policymakers take into account the very real risk of resistance to the drug upon prolonged widespread use (months?) not unlike what happened with early HIV antiviral. We need an antiviral cocktail to combat drug resistance but we aren’t hearing enough about this potential problem and how to address it in a timely matter. Based on current track record, I suspect we will once again be behind the curve (reactive instead of proactive).

  • Can you have blood work to tell you how much of a response you have had to the booster, and vaccine? I am patient in US on Ocrevus for two years. Had two Moderna shots and a third as well. I am unclear whether the third dose was a full vaccine or a booster. Is the volume different depending on whether you are classified as immunocompromised? I have asked Neuro but have yet to hear back and my vaccine card does not specify the dosage I received. Just says the lot # and Moderna.

    Regardless, some time after first two doses, my physician sent me to lab for blood work and could see that I had developed antibodies. ((I had no antibodies prior to the two shots). But they said that they could not tell me how much of a response – the level of antibodies. Clearly from the studies, they can check the response level. Is this not commonly done in day to day clinic care? What lab test/blood draw should I request to actually check levels?

    • Yep but many neuros have kept their head in the sand and said I don’t know…..but I think this has not helped people to make choices

      • When I inquired further about the Spike Protein antibody test I had and it just being yes/no – to the head of lab services/Dir of Chemistry at the lab my physician uses (this is large academic medical center) this is the response: “Our assay is semi-quantitative and does generate a number but in conjunction with infectious disease, we’ve chosen to suppress the number and report results as pos/neg as there’s no way to interpret what the number means. The assay can only say whether antibodies are present but the threshold for protective immunity is completely unknown at this point.” So, I do not know my results.

        I imagine having 4,000x rather 10x amount of response would be better. Correct? What is an antibody number that may be typical in a “normal”, vaccinated patient vs. someone on Ocrevus? I am going to continue conversation and see if I can get a number. Can you explain to me, a non-clinician, what ranges and units should I be discussing with them?

        No matter what I am going to still mask and social distance but if I can find out I had 10x antibodies rather than x antibodies produced it would be reassuring to me.

        Thank you – Happy New Year!

        • Each test has a different threshold 4.000 would be more than 10 but it depends how it works some tests pick up IgM, IgG and IgA one molecule of IgM could be the same as one or 9 molecules of IgG. this is where the problem arises

    • Qualitative antibody test will just tell you present or not. Quantitative antibody test will give an antibody titer or a specific number based on the type of test. Normally the result will have a cut off value for reference.

  • Can you quantify what they mean when they say only the person with “measurable B cells” seroconverted as in how many B cells?

  • Would love to hear your thoughts on pre-exposure prophylaxis EVUSHELD that has received emergency authorization in the US. MS Society hasn’t provided guidance beyond “talk with your doctor”.

    • The problem is omicron evusheld is not very good against this variant of otherwise a reasonable approach if high.levels of in nfection around

      • Knowing that Regen-Cov lasts for 6+ months, I presume sotrovimab (which allgegedly works fairly well against omicron) would probably be a better option but good luck getting any…

        • Sotrovimab inhibits omicrom compared to the regeneron antibody but it has not been designed to hang around in the circulation

  • Just finished Mavenclad year one a few weeks ago.
    Had my 3rd covid vaccine in October before starting Mavenclad.
    Should I get my booster now or wait weeks or maybe months to get a proper response?

    • No association has been demonstrated between the delay after Cladribine administration and immunisation response. The response appears similar to people not on immunotheraphy.

By MouseDoctor



Recent Posts

Recent Comments