78 Comments
Oct 9, 2021Liked by Gavin Giovannoni

I had never heard of a third dose until I read this. Unfortunately when you only get ten minutes ,once a year on the telephone with your consultant , it is impossible to have any of this information. I had to hustle the GP to get the second dose of the vaccine prior to my last infusion of Ocrevus in April otherwise both would have fallen around the same time. I only did this as I had read information from the International MS Federation. Someone who doesn't actively try to keep up with the latest MS information would have no chance of having vaccines at optimal times as one part of the NHS doesn't talk to another. I enjoy reading your newsletters, lots of good information but hard to put into practice within the confines of the NHS.

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Oct 9, 2021Liked by Gavin Giovannoni

totally agree... I follow this newsletter and blog and I still get confused to be honest..

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Hannah, please ask questions. The whole purpose of MS-Selfie is to deal with your queries and to try and unconfuse you ;-)

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Oct 9, 2021Liked by Gavin Giovannoni

Thank you Prof G! Most of the time things are very clear on here but I think with the vaccine stuff I just find it all hard to follow sometimes. It would definitely be even worse without your blogs!! My GP also hadn’t contacted me until I asked them about the 3rd dose last week, then they said I can have it whenever I want. I asked the ms nurse on timing and suggested the best time is December. My last Ocrevus was August. Next one would next next Feb. My first AZ vaccine I had 3 weeks before a full dose of Ocrevus and I didn’t mount the response as the above example. I guess I am still wondering if timing really actually matters? Especially if you’re not going to bother postponing any infusions (which I wouldn’t be bothered to do) e.g why would the 3rd dose act any differently to the other two? Second vaccine was in May, with an infusion in the August. I also look forward to hearing the full barts antibody blood spot results :)

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As I have said in the Newsletter even if you don't mount an antibody response the 3rd dose could be boosting your T-cell immunity. The December recommendation, i.e. 3 months after your last infusion is from the VELOCE study. The 3 months is the minimum, but you need to put allow at least 2-4 weeks after your vaccination before the next infusion to allow a memory and plasma cell response to develop. Plasma cells are not depleted by anti-CD20 therapies.

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Ah ok that does make sense now! Thank you

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The 3rd dose was announced more than a month ago. Your GP or family doctor or MS team should have contacted you if you are immunosuppressive therapies.

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Oct 9, 2021Liked by Gavin Giovannoni

I’m on ocrevus but my GP and neurologist just keep referring to the booster programme not the 3rd primary 🙄 Luckily I’m not giving up and continue to pester both about it

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My understanding is that you are eligible for the 3rd dose; the differences are that you don't have to wait 6 months and you will still be eligible for the 6-month booster after the 3rd dose. So fight your corner.

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Oct 13, 2021Liked by Gavin Giovannoni

This appears to be my neurologist’s final thoughts on this

“I am attending ECTRIMS 2021 ( international world conference in MS), the general consensus for Ocrevus medicine is to give Booster of Covid Vaccine 3-5 months later after the Ocrevus infusion. I am not informed about 3d dose of anti- Covid vaccination, so I cannot comment it in more detail”

Looks like I’m against a brick wall now. However, as my next infusion is in Jan and I had my 1st and 2nd jabs in Mar/Apr my plan is to get my booster in Dec 4 weeks before my infusion and worry about any booster 6 months later. Hopefully they’ll be more clarity then ☺️

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Thanks ☺️ I intend to. My neurologist doesn’t seem all that up to date and her timings are 4 weeks either side of ocrevus is ok for the jab. Thank goodness for your blogs to keep us informed ☺️

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Nov 18, 2021Liked by Gavin Giovannoni

Since my original post, I’ve now been sent info from my neurologist confirming that I should have 3 vaccines 8-12 weeks apart followed by a booster at 6 months. I do agree with them that the confusion has arisen as it’s been months since most of us have had our 2nd dose so the 3rd dose and booster terms have been used interchangeably. However, I’ve now spoken to my surgery and they’ve agreed to flag my records and contact me in April (6 months after my 3rd jab) for a booster. I appreciate that the timing is a bit all over the place but I should get 4 doses in all by April. Whether I’ve made any response remains to be seen though.

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The Norwegian data on use of the Moderna vaccine in patients who have not made an antibody response to two doses of the COVID-19 vaccine in anti-CD20 treated patients is very reassuring. However, the data in fingolimod-treated patients is very disappointing.

König et al. medRxiv preprint doi: https://doi.org/10.1101/2021.10.15.21264977

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Oct 9, 2021Liked by Gavin Giovannoni

No contact from anyone, I did have the booster dose a couple of weeks ago six months after the second vaccine. Will just carry on being super careful. Thanks for taking the time to respond.

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Oct 9, 2021Liked by Gavin Giovannoni

This is amazing as always- it’s been impossible to get advice on this from other sources and I am especially impressed and grateful that you have been willing to stick your neck out when there wasn’t much data to say this is what there is and what I think. The MS community really needs this kind of support.

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As I say this is my opinion and should be interpreted as such.

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Absolutely. Which is why giving it is so appreciated as it’s all too easy to say no comment when it’s an evolving situation. No one should believe that HCPs are infallible but it’s helpful to have the opinion of someone with knowledge and then we can all choose our own paths. The sense that you care about the MS community is really great.

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Hi Dr Giovannoi, a bit of a complicated question that's very specific to my situation. I had about 150mg of Ocrevus (a quarter of the full dose) as I was pulled off the treatment due to a reaction, am due to start Kesimpta soon. I had my third jab a few days ago just over 14 weeks after that infusion, I am still waiting to be moved to a new treatment. I was fully vaccinated prior to starting Ocrevus. I'm just wondering what that means for my immune picture as I've been unable to find answers? My assumption is because of the small dose and vaccination prior to starting I would have mounted a good response, but very unclear on how that would work. (team have assured me 150mg is still protecting me in the short term whilst we wait to move to Kesimpta, which should be very soon.)

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Matthew, you are likely to be fine. Any chance of getting your anti-spike SARS-CoV-2 antibodies checked? This will tell you if you have seroconverted.

I agree 150mg is a pretty good dose and is equivalent to 900mg of rituximab and enough to flatten your B-cell counts.

Please note that booster vaccine responses, i.e. to a recall antigen, are relatively preserved even in patients with no B-cells, which augurs well for the response to your 3rd dose of the vaccine.

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Hi Prof G! I managed to convince them to test my antibodies as a part of my screening for Kesimpta and it confirmed I have seroconverted! Quite a relief! Still not entirely sure how to behave as I also live with immunocompromised family still who haven't been fortunate enough to test their antibody levels, but at least from my perspective that's very good news!

The lymphocyte count in my blood results confused me though. Lymphocyte count is 1.9 10*9/L now vs 1.8 10*9/L just before I had my Ocrevus dose at the beginning of July? Does this mean my B Cells have replenished or is this too general to gain any info on what is happening with my B Cells?

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That is good news; ~30% of ocrelizumab-treated patients will seroconvert. Please be aware that this immunity is to the originator strain of SARS-CoV-2 and as new variants emerge immunity to the originator-vaccine will get weaker.

Yes, you are correct the total or absolute peripheral blood lymphocyte count cannot be used as a proxy for B-cell counts. These need to be tested separately.

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Hi Prof G, had another question I hope you might be able to offer some guidance on. I should be starting Kesimpta imminently, following my 150mg dose of Ocrevus in early July. I have had three doses as part of my primary schedule and have seroconverted, but have not received my 4th booster jab, I would be eligible early next month. I understand with new data that people who have not had a booster fair poorly against Omicron, in terms of preventing infection. I'm wondering if it's worth delaying Kesimpta until I receive my booster? I don't know how much longer the 150mg of Ocrevus would be considered protective, now we are 5 months out. But I'm also keen to make sure I am as protected as possible as I live with and support vulnerable immunosuppressed family.

My question is: is it safer to prioritize MS and get on Kesimpta and worry about the jab later? Or has Ocrevus bought me enough time to get on the booster jab before I start Kesimpta, without compromising MS treatment? Any thoughts you have would extremely appreciated.

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You are right when you say you probably need high antibody levels to protect you from getting Omicron, but it seems that those who get the infection tend to have mild disease. This strain may be an attenuated strain. You also have to remember we now have antiviral therapies for the SARS-CoV-2 that are being given to vulnerable people, such as pwMS on anti-CD20 therapies.

I note you have only had one quarter-dose of ocrelizumab. The dose of ocrelizumab is usually 300mg x 2 in the beginning then 600mg every 6 months.

I am not sure how active your MS is, but I would be doubtful that one infusion of a quarter dose of ocrelizumab would be sufficient to treat your MS. This is why on balance I think treating your MS is probably on balance more important than optimising your immune response to SARS-CoV-2. As you know the latter is a moving target.

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Hi Prof G, have received incredibly bad news that my move to Kesimpta that was due to happen before the end of the year has been delayed indefinitely, because the hospital does not have the capacity at present whilst preparing for an Omicron wave. Because they halted my infusion of Ocrevus out of concern they want me to have my first dose of Kesimpta in hospital, which can no longer be facilitated. It seems like it could be a couple months before they can start me on Kesimpta.

I need to ask, but how much good will the small 150mg dose of Ocrevus I received be doing me this far out, between 5 and 6 months later? You mentioned that you felt it was about equivalent to a 900mg dose of Rituximab and I just want some hope that this dose can carry me through the next couple months. It's been hard to get ahold of anyone at my hospital in the chaos and just hoping for some answers. Unsure what to do.

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Yes, I had a reaction, or more likely my team overreacted to an infusion reaction and pulled me off when they didn't need to (having spoken to an immunologist who cleared me for Kesimpta.) You did mention previously that 150mg was about equivalent to 900mg of Rituximab when I asked about this in the past, and so should be theoretically protective? I will keep this in mind and prioritize starting Kesimpta ASAP (have been trying to fight to get on it faster for months.) My MS so far isn't particularly active. Two attacks five years apart and I've fully recovered from both, about 6 lesions total on MRI scans, but am key to get on high efficacy therapy to give me the best chance.

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Yes, I got barely 24 hours of enjoying the fact I have antibodies before hearing about the new highly transmissible immune escape variant out of South Africa! Very worrying, let's hope it loses steam and doesn't outpace Delta.

With a new variant demonstrating a high level of immune escape likely requiring a new vaccine in the near future, out of curiosity would a new vaccine still be a recall antigen, or would that be back to square one from a depleted B cell perspective? Would they need to let my B Cells recover again if the vaccines are reformulated for a newer variant?

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Thank you so much for your response! Planning to ask my team if I can have this done during my screening for Kesimpta. I did ask during Ocrevus screening though and they said it wasn't something they were doing. It's definitely something I would like though (I live with other vulnerable family members as well.)

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Oct 20, 2021Liked by Gavin Giovannoni

Sorry I’m very confused. I have just had the booster jab this week and i am on ocrevus. So do i still have to have a third primary covid vaccine ? Can i have it if i’ve already had the booster jab?

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Susan. you just need to make sure your booster jab gets redefined as the 3rd jab when the NHS app allows it and then you will be able to have the 4th dose in 6 months time that will be your 'true booster' dose. I hope that makes sense?

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Oct 11, 2021Liked by Gavin Giovannoni

Prof G, I am intrigued by your ecplanation of immunology 101 and why the flu vaccine works different with Ocrevus-users then the covid19 vaccine does.

How does this work when one DID have an antibody response to the first and second vaccine (AZ)? I postponed my Ocrevus in spring and received my vaccinations 7 and 10 months after my last Ocrevus infusion. Tests showed I did have an antibody respons. 5 weeks after my 2nd vaccination I got my new Ocrevus infusion. Now, 3 months after the infusion, I am bound to receive the invite for my third vaccination (‘Cormyaty’, or Pfizer).

Does this mean this third shot will act the same as a flu vaccine for me, as I did have a response before so I might have some ‘memory b-cells’? Or is this too simple a thought?

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Yes, that is the assumption. Once you have a preexisting memory response the booster will increase your titres without germinal centre function. However, the level of boosting as in the VELOCE study was not as good in the ocrelizumab treated subjects compared to the control subjects.

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Thank you so much! As I do have other comorbidities, it is of high importance that I time my third dose and a possible booster as good as possible, but waiting 4-5 months more brings other risks as I will be having to go through winter without a third dose if I choose that route. So I guess it is an acceptable bet to take the third dose in a month or so, instead of waiting when Ocrevus has worn out a little more.

Thanks for your explanations, your work and swift reply.

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Oct 10, 2021Liked by Gavin Giovannoni

Prof G sorry to repeat myself but is it ok to have flu vacc just a few days (<7) before Ocrevus? As otherwise you suggest waiting three months and my son’s next infusion is on Thursday. I’m now wondering if should try and get his flu vaccine ASAP tomorrow but worried that’s too near to the infusion?

This is such a minefield and two hours on the internet have provided every single variation of answer I could imagine without any clarity at all.

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Oct 9, 2021Liked by Gavin Giovannoni

Thanks you for a really useful post. I was not aware of REG-COV or Monupirovir. This is very interesting and an important step forward in the treatment of Covid. Do you think the pandemic will be over soon? It seems that the virus is always one step ahead. Is this going to be like HIV which is no longer a death sentence because it's now treatable?

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The virus is becoming endemic and the UK like other high-income nations will be back to a new normal very soon. The current caseload is largely confined to unvaccinated children and the vaccine-hesitant group eventually her immunity will develop.

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Oct 9, 2021Liked by Gavin Giovannoni

Thank you. I appreciate you so much!

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Oct 9, 2021Liked by Gavin Giovannoni

Thank you Prof G! I got a third jab 3 months after last Ocrevus infusion as that was the “guidance” I gleaned back in early Sept when it was offered. My neuro’s guidance was that he did not object. Wish I’d had this information a month ago. Oy vey…

Now I’m searching for how to get an immunity test - the hunt is real! US based here

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Dare I suggest not getting the immunity test? Only get a test if you can act on the result. If you have not seroconverted you may still have good T-cell immunity? Unless knowing you are seropositive or negative is going to change your behaviour.

I was offered an antibody test in my own lab and I said no. Ignorance is bliss; I want to get back to normal life as soon as possible. However, it is easy for me to say this as I am not on immunosuppressive therapy and I am at relatively low risk of getting severe COVID-19.

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This is a good point about that test. As someone else on Ocrevus I did the test because I was curious and I felt worse about it when I got the shitty results 😂 For a few days afterwards I wished I didn’t know to be honest. I was hoping I’d be the special percentage who did convert 😇 obviously not!!! Saying that, after about a week I forgot about it and have continued to get on with life.. to be honest. Also the news of the other drugs now becoming available in a “worst case scenario” for treatment is also a comforting feeling

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Thank you for sharing this perspective. Glad you dared to do so! I would like to know - but perhaps ignorance is indeed bliss….good thought pattern shifting words….

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Oct 9, 2021Liked by Gavin Giovannoni

Hi Dr. G. Thanks for the post. It was very informative in an area that is often very gray. I was wondering if you have any information you could direct us to around vaccinations outside of flu and COVID-19. For example, anything around removing immunity from vaccines you've had as a child (chicken pox etc), as well as potentially vaccines you might take during Ocrevus like HPV? Thanks!

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Jenn, I address the flu vaccine in the post. Try and delay it until 3 months after your last ocrelizumab/rituximab dose. I have no idea what to do with ofatumumab, but suggest going ahead and having it when you are invited to have the vaccine. With all the other DMTs go ahead and have when you can.

HPV is more complex and I will do a separate Newsletter on it because it depends if it is an upgrade of the quadrivalent vaccine or first-time immunity.

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Thank you so much! Yes - the flu I knew - it was more about the things you "one and done" like chicken pox etc. Looking forward to hearing more about HPV as well - for me my first vaccine was while on Ocrevus (5 months after my last infusion) - really appreciate all that you share!

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Oct 9, 2021Liked by Gavin Giovannoni

Hi

" The latter is my current advice for older patients and those with comorbidities who are at high risk of getting severe COVID-19. These people need as much anti-SARS-CoV-2 immunity as possible to protect themselves from getting severe COVID-19 during the pandemic, i.e. in the next few months before the pandemic abates. In younger patients at very low risk of severe COVID-19 optimising their immunity now is not that important and they can probably wait for the booster."

Where you talk about all the patients with comorbidities are you referring to those on ocrelizumab or those people including those on no DMT?

Also the recently approved treatment you mentioned which you say should be available to immunosuppressed Ms patients should this also be available to Ms patients who are not immunosuppressed but are are more progressed and therefore vulnerable?

Many thanks

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Re: "should this also be available to MS patients who are not immunosuppressed but are more progressed and therefore vulnerable."

No, the 3rd dose does not apply to them, but the booster dose will.

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Oct 9, 2021Liked by Gavin Giovannoni

Hi many thanks for the prompt reply but this second question actually related to the approved antiviral you mention.

Do you think vulnerable progressed MS not on DMTs would qualify for the antiviral REGEN?

'I am sure you are aware that REGEN-COV has just be licensed by the MHRA and is likely to become available on the NHS to treat acute COVID-19 in vulnerable patients. REGEN-COV is a combination of two monoclonal antibodies (Casirivimab and Iimdevimab) against SARS-CoV-2, which if started after developing COVID-19 reduces your chances of getting severe COVID-19 by 70%. I am sure the NHS will make REGEN-COV available to people with MS on anti-CD20 therapies in the event of them getting COVID-19 in the near future. In addition, a small molecule anti-viral '

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The third dose is quite specific to patients on immunosuppressive therapies and does not apply to all patients with MS on DMTs.

The booster however applies to over 50s and vulnerable people. My interpretation of the latter is that all pwMS are vulnerable.

Yes, when I am talking about comorbidities I am referring to pwMS on anti-CD20 therapy. The pwMS on ocrelizumab most at risk of dying from COVID-19 are those over the age of 50 and those with one or more comorbidities.

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Oct 9, 2021Liked by Gavin Giovannoni

Thanks so much for all this info, it is so helpful and great of you to share it with us. I don’t think a third dose is on offer here but in any case it is almost 6 months since my second dose of Pfizer/Biontech. I delayed my last infusion and got my first vaccine 7 months post treatment but I still didn’t make any antibodies. My main concern with Covid (other than obvious hospitalisation and death) is that it will set my rehabilitation back by months if I get it. I have worked so hard to get from using a wheelchair to walking pain free and the slightest thing can throw me right back. I was considering delaying my next treatment again but other than my first two doses of Ocrevus each of my infusions has been 10 months apart because of Covid and I’m worried this will effect how it works!? I feel so good on this treatment but the Covid anxiety and isolation is tough.

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Rosie, I think you will be okay delaying your next dose. Many of us in the field of MS think anti-CD20 therapies can be used as IRTs (immune reconstitution therapies) so delaying the next dose to try and optimise your vaccine immunity makes sense. You are correct COVID-19 is more than just COVID-19, the effect on pwMS in terms of long COVID should not be underestimated.

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Hi Dr G !! I have MS and I can't thank enough for all your work with us, pwMS!!

In my case I was treated with alemtuzumab in fev/2019 and fev/2020, currently with low levels of B and T cells (<600), i had 2 doses in July, after each dose my tyroide function went nuts, I am now being treated to control tyroide function (hyper).

Should I test my antibodies response prior to a 3rd jab?

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No just go ahead and get the jab. If you want you can get ask to test your immunity later.

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Oct 9, 2021Liked by Gavin Giovannoni

Extremely helpful post. Thank you for all that you do for this community.

Question: is it safe to have a flu vaccine a couple days before a Tysabri infusion?

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Re: "is it safe to have a flu vaccine a couple of days before a Tysabri infusion?"

Yes, no reason why not.

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Oct 9, 2021Liked by Gavin Giovannoni

And same for a few days before Ocrevus?

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Ideally, you need to allow at least 2-4 weeks after your vaccination before the next infusion to allow a memory and plasma cell response to develop. Plasma cells are not depleted by anti-CD20 therapies and will therefore continue to make antibodies. If you deplete B-cells before the newly selected ones can become plasma cells you will abrogate the effect of the vaccine.

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Oct 9, 2021Liked by Gavin Giovannoni

Thank you so much. This blog really is so empowering. First ocr last week so presumably will follow the booster timing advice - am only eligible for booster, not third primary.

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Oct 9, 2021Liked by Gavin Giovannoni

Can I clarify with the flu jab and Ocrevus- if best to be 3 month post infusion but infusion due in less than a week so that would mean flu jab in January essentially missing the worst of the season, is it better to have it now and is < 7 days acceptable?

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This highlights the problem with the flu vaccine and its timing. I agree with you that if you want to be covered now for the flu it makes no sense to wait several months. So I would go for it and get vaccinated and hope it is good enough to induce new T-cell memory that will protect you.

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