#MSCOVID19 The Key is the T cell response, and the vaccine response is not affected by variants.

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We are now firmly in vaccine mode and the race is on to determine what are the effects of MS drugs on the vaccine responses. The real world vaccine responses of health care workers and care home people are already published in pre print form and I have to say already been replicated in a number of studies. There are no surprises so far. Although a few people get a late stage injection reactions (a week after injection) with the Moderna vaccine, but this is irrelevant as we haven’t had any of that vaccine yet in the UK. I bet it means the protein made by the RNA is present for over a week and you vaccinate and get an immune responses and then the immune response attacks the vaccine protein still present in the tissue.

As you can see you get an antibody response after the first Pfizer vaccine and it raises abit for the second injection. However, if you have had COVID-19 you are more likely to get a maximal response after the first dose. However, this is not always the case and best protection is after the two doses, unless you get a single shot vaccine.

Ebinger et al. 2022 MedRXiv

For people on a twelve week dosing cycle as in the UK, I suspect we will see a deluge of these papers in the next week or three. First the case reports, then a few people and then studies in thousands of people.

However, this is not what we want to know.

Based on what is in the treatment labels from the FDA and EMA, fingolimod and ocrelizumab are the most likely continouously administered agents to blunt the vaccine antibody responses. Although is may be possible that alemtuzumab and clabribine can influence vaccination when cells are depleted, that alemtuzumab can induce anti-drug antibodies in 60-80+% of people within one month of infusion when there is not a T and B cell in sight in the blood suggests that I may be worrying for no reason. It was also clear, based on the ACTRIMS 2021 presentations that vaccine responses occurred in cladribine treated people even when immune-depleted.

However, let’s face it we all know (deep down) that ocrelizumab and rituximab are going to be the problem children as far as MS drugs and vaccinations are concerned. If there are no B cells present and repeatedly depleted, your ability to generate new B cells responses is likely to be curtailed. However, the impact on dosing in relation to time after infusion is going to be key information that we need to know. It could be you make and antibody response and it quickly disappears.

I may be wrong and importantly, even if the levels are curtailed it may be enough to be protective. But what is protective? There is “sterilizing immunity” which means your immune response is so hot that if you get infected then the imune response is so good that you get rid of the virus and you can’t pass it on. However, I suspect that people may get re-infected. The occurence of this is low but it does happen. However, the important point is that you get rid of the virus more quickly if you have immunity to it. You don’t want Long-COVID and this problem hangs around for many months in some people. You get immunity by vaccination.

Immunity may wane with time just like it will in people who are not on a DMT, however even though the antibody responses have waned there is still immunological memory and you will get rid of the virus before it can do too much. . However, I have suggested that you can get rid of the COVID-19 without the need for antibodies.

So the key experiment is going to be what is the T cell response to the vaccines going to be. But one thing I can say is that the T cell response is different to the B cell responses and whilst some people may need higher levels of antibody to get rid of the South African and Brazilians variants, at the T cell level they are all toast. In this study they have taken T cells from people vaccinated with the RNA vaccines to see if the T cell response to the original Chinese variant, the UK variant, the South African variant the Brazilian variant are different. They aren’t. Therefore, if you get infected with the South Africa variant your T cells will deal with it.

What has this got to do with MS?

Will the T cell response be intact or blunted? This will provide insight into how ocrelizumab works in MS. If you can’t make a T cell responses to the vaccine, maybe you can’t you make a T cell response in MS. Likewise if you can then you can and suggests that T cells responses can be generated in MS. If true then it suggests the idea that ocrelizumab works by inhibiting T cells via antigen presentation may be wrong. I hope a CD8 T cell response is made as it will be anti-viral. The beauty of this is we will get the real answer soon as loads of labs will be doing this experiment. As a scientist I look forward to see what happens. Eitherway

T cell responses to differnt viral varients

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MouseDoctor

13 comments

  • I have been on Tysabri for 5 years. In March last year my husband was very ill for two weeks and although not tested we are pretty sure he had COVID. At the time I just had a sore throat. Last week I had the AZ Vaccine. Within 12 hours I was running a temperature of over 101 and I slept for at least 40 of the following 48 hours. Given the risk of illness causing MS relapses I was very anxious and regretted by decision to have the vaccine bitterly. Following this experience I think I have developed a strong immune response to COVID and do not want the second vaccine. Do I really need it? Based on your article I don’t think I do. How can I prove I don’t?

    • There is a post that could be done on this subject matter as there are lots of posts on the influence of prior exposure to COVID-19.

  • Hi MD – is there a way for patients to measure their immune response to the vaccine after taking it? One of my doctors suggested that I get an antibody test 3-4 weeks after my last vaccine dose, but another one said that vaccine response can’t be measured by the antibody tests accurately for anyone. I’ve been on Ocrelizumab for years, so I want to know if it’s safe for me to interact with people after I’ve been vaccinated!

    • I disagree and agree with your neuro.

      To see how much reponse you make 2-4 weeks would be OK, for the pzifer vaccine the maximum response is made in most people within 7 days. 3-4 weeks will give you the same answer. If you get the one off vaccine 3-4 weeks would be better.

      The way to see if you have responded to the vaccine is indeed to get an antibody test and for people interested then contact mscovid19Ab@qmul.ac.uk and get a blood spot test in the post. The guys and gals from BartsMS will call you. We have had over 200 cards back already and have vaccinated over 350 people with MS and understand 400 people on ocrelizumab have been offered a vaccination. Our test can measure the nucleocapsid and the spike (receptor binding domain) response, this can distinguish between a vaccine response and a natural infection.

      However there are vaccination tests and vaccination tests, some give you a yes and no answer and this is no good and importantly others give you a response to nucleocapsid and this is no good as the vaccine is to Spike. I would want a receptor binding domain of spike test. It gives you an idea of the viral inhibition test. Now the question is what is a protective level. The answer isn’t known but it is predicted that 20% of the convalescent serum level will be protective. I was going to do a post on this. However with ocrelizumab it may be a question if you make an antibody response not how much. For immunosuppressed kidney transplant recipients it is 90% don’t make and antibody response. Maybe we should have a COVID19 saturday like we used to do a CCSVI weekly

      • do i get that right that there is pretty low probability of getting any vaccination protection under ocrevus/ritux? thought at least t-cell immunity is likely – and why then vaccination is recommended – vaccinated people under ocrevus might feel protected but aren‘t…or do i confuse things?

        • The answer we do not know what will happen unless vaccinated people show evidence of COVID but if they dont them they are protected. The point is although you may have a blunted B cell response, it is less likely to be no response. Importantly it is likely you will get a T cell response and this paper says that you dont have to worry if is a south african, brazilian hollywood etc etc etc as the T cells can get rid of them all. Likewise as ocrelizumab is available for people with progressive disease then it is important as the risk factor is progressive disease about 1.7 times higher risk of hospitalization and a thee times higher risk than ICU admission

      • Hi MD – does your study extend outside of the UK? I’m based in the US. Happy to do any legwork needed on this side of the pond to get you data that would be useful for your study.

  • that alemtuzumab can induce anti-drug antibodies in 60-80+% of people within one month of infusion when there is not a T and B cell in sight in the blood

    Maybe you have to look at the bone marrow ,spleen ,lymph nodes ,tonsils etc

    Biopsy all those places …….Caneco .(

    Will the T cell response be intact or blunted? This will provide insight into how ocrelizumab works in MS. If you can’t make a T cell responses to the vaccine, maybe you can’t you make a T cell response in MS. Likewise if you can then you can and suggests that T cells responses can be generated in MS. If true then it suggests the idea that ocrelizumab works by inhibiting T cells via antigen presentation may be wrong.

    It a do or die moment for the Doc Mouse theory 😉

    However do we have data from cancer patients, on anti cd 20 theraphy or lupus patients?

    • Have to look in lymph nodes boone marrow… yep

      Do or die…Not really I can explain both ways….but some of my colleagues will find it hard.

      Anti-CD20 for cancer patiets yes we do

  • getting pfizer jab in the us this week 6 weeks after ocrelizumab. Nervous about being a lab rat and a bit scared of what inflammatory response will do to ms but excited for at least partial vaccination!
    Keep the data coming!

  • MD am I right in thinking that we don’t get an individual response from Dr Ruth’s study if we send our blood spots? I would love to know whether mine which I sent previously were positive.

    • The original study was planned to be a seroprevalence study (how common have people with MS being infected) and I think originally it was annonymous. NDG also is doing another survey and that was going to be annonymous, but in the ethical review got that changed. However with vaccines comming along it potentially allows you to look for vaccine responders. The original aim was to screen against nucleocapsid antigen, which would be no use for detecting a vaccine response as the vaccine is against Spike. I think it is now clear that there is a problem because of two things (a) The antibody response in many people is not long-lasting and therefore people infected during the first wave may be low or appear negative if blood is tested months after the infection (b) There is clearly cross-reactivity with other viruses (cold-causing cornavirus) as we are detecting clear positives from 2017 samples so what is a negative, negative as this means some positives will be classed as negatives. However we have now made receptor binding domain test for spike and this can pick up vaccine responses and we have seen people positive on one and not on the other. So this may help, but it means double the work. We have been excluded from the labs since November by our mamagement, I and others have made the cases as has Dr Ruth and there was no joy from management. It is a massive failing that I am embarassed and frustrated with. They didn’t view this as essential work. The problem is the labs are not made for social distancing and the lab managers have gone health and safety and paperwork crazy with nothing to do for a year. They have created red tape a plenty. We had to get a grant, which we didnt need, to go into the labs and wasted 8 weeks and the dont get me started on the ethics.

      Had we been able to get into the labs, we would have had the Worlds first case report of vaccination on ocrelizumab, and I am sure they will come. Israel will beat will be the first source of news on the pfizer jab and maybe US to. The UK can have the Astrazeneca jab….But many countries will say who cares we are not using it:-(

      We were allowed back in a week ago, we have the receptor binding domain assay up and running but now we have a four month backlog of samples, in addition to our other stuff, that we are working through. The majority of the ocrelizumab studies will read out in April when the people who were vaccinated will be sending their post bleeds back. However we plan to start on samples next week. We only have codes and so dont know who is who, but to me it would be reasonable to send information back. However, what that means is difficult to know but obviously a high and low response can be called. Please bear with us. We want to get a paper out ASAP so we are doing what we can Hopefully we will get back to you soon.

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