The Third Dose verses the Booster


This was addressed in ProfGs MS selfie I think

The Booster

This issue is causing people problems. For people not on disease modifying drugs and therefore likely to have made a COVID vaccine response. You get your first dose and then your second dose 3-12 weeks later. You then can have a BOOSTER 6 months later.

This is currently open to anyone over 40 in UK. This in my mind should mean anyone with MS and their household contacts, but in some places they are offering boosters to anyone who wants one.

Why are they doing this?

A vaccination creates a B cell and antibody response and a protective T cell response.

Antibodies can directly target the SARS-CoV-2 virus and neutralize it and therefore can prevent infection from occuring.

In contrast the T cell does not see the virus but sees a cell that has virus particles, therefore you have been infected before your T cells start working.

Therefore the best bit of the vaccine is to create a high and long lasting level of antibodies. However, we have been hiding ourselves and so are not coming into contact with the virus when we have high levels of antibody. Doing this would give you a natural boost and perhaps explains why health care workers lose their antibody levels stower than someone older even if they have been naturally infected

In natural Infection antibody levels wane over time

Following vaccination the antibody levels will wane over time, you will about half of them each month. If you were vaccinated with astrazeneca and have not been infected your antibody levels start off at a lower place than pfizer/moderna and so have the opportunitity to wane.

In vaccinated people antibody levels wane over time

Now the important element is what is the level required to neutralise the virus. Once your antibody levels drop below this means you can get infected and pass the virus onto someone else. In most cases your memory B cells and plasma cells and T cells will then kick in to make more antibody and stat killing off infected cells.

In the graph on the right it shows the antibody levels created by the vaccines and the blue means there is enough to stop infection but the red means you can be infected and you can see with the RNA vaccines the antibody levels are higher than the adenoviral vaccines and higher than the inactivated whole virus (This has the advantage the breath of the immune response is greater and so good for gtting more T cells going).

No the problem is this information is not based on the the problem right now and this is DELTA

The proteotypic virus strain is Wuhan. But more recently the problem was alpha also known as Kent or UK strain. This has an infectious advantage over wuhan and by March 2021 nearly all infections was due to alpha. This requires twice the amount of antibody to get rid of it. But as you can see by July 2021 nearly all infections were delta or indian variant. This is highly infective and also has immune escape mutations and so you need 3 times more antibody to get rid of it. Now if you antibody levels are falling and delta is around then the chances of getting infected increases and that is why double vaxers are getting infected.

However you can now see why South Africa gave up on the Astrazeneca because it wasnt giving enough protection. This is because beta was circulating and it has immune escape variants and needs 6 times more antibody to get rid of it (Bottom right above). You can also see why people are concerned about Mu (Columbian) because it needs 7-12 times more antibody to get rid of it. At the moment this has not taken hold because it does not have the infectivity as seen with delta, but if if of the sun or daughter of mu arrives then infections will rise.

This is the reason why RNA vaccines are being used for booster jabs in the UK are using the RNA vaccines for the booster. This mix and match works and gives a better response than AZ/AZ when it is AZ/Pfizer or AZ/Moderna. So if you have been offered a booster (I got a text from NHS) take it and this is especially important if you have been JnJ or AZ vaccinated. The boost will get you antibody levels up. In my family those catching COVID after being double vaxed recieved AZ. The vaccine creating the highest antibody levels has oofered the best protection against delta infection.

However, the vaccines are protective against severe disease and this is why it is worth getting jabbed. especially as this virus is going to be with us for a long, long, long time.

As you can see the first wave in March was deadly as we reduced our pension requirements by infcting the old people in homes. We quelled the virus by lockdown and then everyone went mad of the summer holidays to give a deadly second wave as more people got infected and now we have vaccine confidence we are all let out again to go crazy and forget about the virus..until it infectes us but the vaccine is protecting most from death.

When the virus first arrived it was suggested that 60% of the population needed to be infected to get Hed Immunity where by the the virus ould not transmit. However experience in Brazil soon showed us that was wrong and the virus was going crazy with about 80% infection (see references above for details).

However in my opinion we will never get herd immunity to this virus unless it mutates to a dead end, or technology defeats it, because we will be constantly providing the virus with people that it can infect especially as the vaccination programes all over the world are not in synchronicity. For most it will turn into a cold and it will kill more than the flu ( unless treated). We will have to learn to live (and die) with this.

However if you are on certain DMT you may not have the luxuary of a protective antibody and T cell response and for such people the idea is to give a third dose of the vaccine. This is different to a straight boost as after the third dose you would get a booster 6 months later. But there is confusion. This becaus the decision to give a thrid dose is over six months for most people who had the second dose. However it is different from the booste.

Who can get the Boost: Currently anyone over 50 and people at high risk. This included people with chronic neurological disease (green book chaper 14a page 14) that includes MS. I am sure you could made the case to ask for a booster and remeber disability and progression are risk factors for more severe disease.

Who can get a booster

If you have MS you are eligible under table 3. But also note that you partners should be eligble too

Green Book Chaper 14a

Green Book chaper 14a pg 15

You can make that argument that any DMT is immunomodulatory that is why it they are used, I would argue they are all immunosuppressive, but I guess they there is a definition, they would clearly aim to inhibit relapses that could be treated with steroids and so would be steroid saving. If arthrits , lupus, arthritis are included then multiple sclerosis must be also.

The Third Dose

In August 2021, JCVI recommended a third primary dose of vaccination for individuals who
were severely immunosuppressed when they received their first or second dose of COVID19 vaccination (see below).

So you would get Dose 1 4-8 weeks, Dose 2 4-8 weeks Dose 3 6 months Booster. The problem is for many people they are already past 6 months. However with a thrid dose the implication is that you will be offered a booster in the future. For some people e.g. those on anti CD20 it may take 3 (or more jabs) to get an antibody response

In my mind this this could mean alemtuzumab, cladribine, ocrelizumab, ofatumumab (other CD20 depleters), fingolimod, ozanimod, ponesimod, spiponimod and could also be dimethyl fumarate as some people exhibit notable lymphopenia. Remember I am not a Doctor and are not giving advice.

However you can consult the Association of British neurologist website for their recommendations however remember that last JCVI update was 15 Novemeber 2021 so advice before that maay be out of date

Once you are a few months after alemtuzumab and cladribine the cells have returned. You can make responses, typically as good as none-immunosuppressed people. However, we know that people taking sphingosine-1-phopshate modulators and CD20-depleting antibodies often do not make or make a weak response to vaccination.

Page 22

The third dose is available for people who are

COI None considered 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 and are not meant to be interpreted as personal clinical advice.  Please note that Professor Gavin Giovannoni has no responsibility for this blog.

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  • Just to male sure I understand you well. I am writing this question from 11D, where I am on my 3rd Lemtrada day, year 1. I had a COVID booster jab 3 weeks ago.

    Did I need a third jab instead? Do i need to do anything about else at this stage?

    My wife is eligible for a booster as you said and will inform her.

    • Your booster jab three weeks ago will have given you immunity and alemtuzumab should not stop this. I believe you were not on immunosuppressive earlier and so may not have qualified for third dose because you will have made a response it depends on how your GP/Team see this.

  • Thanks MD

    It’s just a pity that not all neurologist’s are up to date with this. Mine says I’m eligible for the booster but has no information about the 3rd primary dose. Therefore, I’ve now had my booster as it’s been 6 months since my 2nd dose but as this has been recorded as a booster and not the 3rd primary I won’t be eligible for the booster in 6 months. I’m on ocrelizumab. I’ve tried sending my neurologist all the JCVI guidelines and green book info but she won’t budge and my GP wants her to decide 🙄

    • By the time you need fourth dose we may all be getting one anyway. I think because the rules are made up by rheumatologists because ocrelizumab is not specifically mentioned some people cant make the jump from rituximab and ocrelizumab…Someone I know is on methotrexate and they simply got a text from NHS because this is mentioned for third doses.

    • 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.

  • tx for providing this summary!
    does it make sense to go for the 3rd jab now (facing the 4th wave) after 6m from last OCR (did not make antibodies after 2nd shot though). my neuro says at least i might get some “training” and with that some higher protection from worst case. and still then further OCR hold out for b-cell repopulation and “booster” shot in a view month?
    i read some norwegian study that the antibody response with 3rd jab was “significantly” better on cd20 (not so with FING unfortunately) but then just 25% went over the “protective” threadshold…

    • Yes 25% who did not respond after 2 made some response after three…this has been seen in some cancer studies also. If you knew your CD19 levels it may help to guide on the chances of a positive response we published info in MedRxiv

  • This is interesting. So maybe it’s a good thing I got pinged last week (and didn’t get sick) because I was potentially exposed to the virus and if I was, the antibodies kicked in and did their job. I caught a nasty cold a few weeks ago that really mucked with my plans, so I’ve been reluctant to go out much in case I get sick again. But on Saturday 6th I went to parkrun in the morning (so outside), volunteered at a food bank with one other person but mostly not in the same room (and clients were all outside and served through a window), then went by bus to the fireworks in the evening. So the only time I was within 2m of anyone for over 15 minutes was in the queue for the fireworks and watching the display. Being outside I think the chance I was actually exposed was very low, but maybe that’s exactly the sort of thing I should be doing more of.

    My last two blood tests have shown my lymphocytes to be higher than usual (around 1.2 – I’m on DMF). Could this be anything to do with a vaccine response or antibody response to a/the virus? My blood tests have been changed to every six months due to the pandemic and my last two happened to fall not long after my second and booster doses.

    • If you get infection etc you white cells go up (cold etc). My queue for fireworks was sardines for 20-30minutes, social distance of about 15cm and no masks. Few viral particles you deal with a sneeze in your face it may be alot more virus and maybe a reason why some doctors and nurses had a rough ride

      • You can bet I wore a mask in that queue! I normally don’t bother if I’m outside but this was far too close for comfort. A few others near me wore masks too. At least we weren’t all facing one another I guess.

  • Again… I am going to throw my 2 cents in. Please people, LISTEN AND PAY ATTENTION TO THE DATA & THE INFO IN THESE BLOGS! 41 people in my State (Massachusetts) this week that were double vaccinated have died from Covid – incl my Dad and there have been 5,313 new breakthrough cases this week of double vaccinated people. This is enough proof to me that the vaccines are losing effectiveness and everyone needs at least the booster if not a 3rd full jab. I am beyond the time table listed here for a full jab but being immune compromised, (t1d as well as MS -no longer on a dmt, and over 50) I am still going to question and push the vaccine clinic for full dose when I go in for the booster.

      • Thank you for that. I originally received Pfizer 1 & 2. 🤔🤔🤔 your thoughts on should I sign up (or rather what would you do if it was you as I know you cannot diagnose or advise treatment) at Moderna clinic this time around or does it matter?

        • FWIW, I tried to switch from Pfizer to Moderna for third dose, was not allowed in my clinic. “I’ll sign a waiver” did not do anything, either.

  • Edited to add that I have today received info from my neurologist to let me know that I am eligible for 3 primary jabs and then a booster 6 months after my 3rd dose. I’ve contacted the surgery so they’ve flagged my records accordingly ☺️

  • So, I am 36 in the U.S. On DMF. Previously had two does of Moderna. I am recovering from a breakthrough infection now. It probably won’t be long before I am an eligible for a booster. My thinking is that I should count the breakthrough Covid as a booster in itself and assume antibodies would wane in six months (rough May 2022). Since that is summer and maybe Covid would become seasonal, get another jab in September to cover me though the winter months?

  • Whatever it’s called, I’ve been advised to hang on til 9 months post ocrelizumab for the next jab in the hope of making a better response. So that’s the end of December. And my AZ doses were end of Jan/feb so a while ago now.

    I’m feeling a wee bit like a sitting duck with two kids who aren’t old enough to be offered the vaccine. Including one at secondary school who I tried to get an early dose for (with support from my hospital team) but no-one would give it to him as it’s not licensed for under 12s so their insurance/professional indemnity won’t cover it. The friend and parental grapevines are full of news of positive cases amongst kids at the moment.

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