Why an optimal vaccine response is desirable in people with MS on immunosuppressive DMT. Don’t be the source of the “Cockney”

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As you know I did a post about why the the COVID-19 is a good example of natural selection as suggested by Charles Darwin. You should have heard about the UK variant, the Brazilian variant, you could also get a Hollywood variant, but you are unlikely to get a French variant.

Why?

No, not because of waxing techniques as there is a French variant there:-). It is not about “Gods will” either but because the French are not testing for variants. If you dont look, you won’t find. I believe the UK sequences over 10% of the COVID tests it does, which is going to be millions each month and the UK has done about half of the World’s SARS-CoV-2 sequences. These are deposited in a public database

You may have heard of the UK variant (B.1.1.7). This variant was first detected in the United Kingdom in Kent (home of the Channel tunnel) towards the end of 2020. It is referred to by some as the “Kent variant”. It has a large number of mutations, many of which involve the virus’ Spike protein, which helps the virus invade human cells. This is used for vaccination. In the Oxford version the spike looks like the Chinese virus Spike and the Moderna/Pfizer versions have two prolines (amino acids) changes that stabilises the structure.

The Kent (UK) variant has spread rapidly throughout the UK (about 80% of tests in January were against this variant), since it emerged, and to at least 70 other countries, including Australia.

The fact it has spread so rapidly, and quickly replaced other circulating variants, suggests it has some sort of selective advantage over other variants (Natural selection). The science Boffs have found that this variant has lots of mutations from the original “Chinese” Variant and one mutation is the E501Y change (Aspartic acid to tyrosine amino acid at position 501 of the spike protein). This mutation has appeared elsewhere and occurs in the South African (B.1.351) variant found in Nelson Mandela Bay, South Africa, in October 2020. (My sources rule out ProfG popping home for a summer holiday as the cause) and now accounts for more than 90% of SARS-CoV-2 samples in South Africa that undergo genetic sequencing. It is also found in the Brazilian variant (B.1.1.28. P.1). This was first picked up in Japan in some Brazilian travellers. Perhaps it should have been the Japanese variant:-). The 501Y variant binds to the target ACE2 more effectively.

The South African variant also has other concerning mutations. Two of these, called “E484K” (A glutamic acid to lysine change at position 484 of Spike) and “K417N” (A Lysine to asparagine), are bad news for our immune system as it can help to allow evasion from the immune system. Like the South African variant, the Brazilian variant has the spike, N501Y and E484K and and variants at position 417 (as well as numerous other mutations). Now that the Kent variant is the base on which the virus will continue to mutate and apparently UK variants with the E484K variant have been found. Others including F490S (Phenylanaline to serine amino acid change) and S494P (Serine to proline) have been found, which may help escape the vaccines. However, remember the vaccines also make a T cell response and whilst the variants above may influence antibody binding it is likely that T cells react to a different bit and will eventually kill the virus, it may be just abit slower so you get a sniffle and a snuffle before that happens.

Another mutation in the Kent variant is L18F (Leucine to phenylanaline) substitution in spike initiated a substrain characterized by replicative advantage of 1.70 [95% CI: 1.56-1.96] in relation to the remaining Kent substrains. Can we call this the “Polish variant” because it was reported by some Polish researchers?

Now if these virus are not transmitted then it not a problem but if it does then new variants can occur and eventually the virus may develop mutations such that it may avoid the vaccination response. This is a concern for people that do not get adequate vaccination cover so that the virus is not eliminated. If it is not eliminated then the virus can be passed on. If it has an advantage it will take over. When you get vaccinated the immune response will pick off the virus that they have been generated to get rid off. If there is mutated virus that avoids some of the immune response the question is can it infect someone, before it is got rid of?

The virus has programmes that limit the number of mutations that occur in the virus as it replicates, which is good news. This means that this occurs slowly. Now the weird thing was the Kent variant had nearly twenty mutations. Why so many? One thought is that the ancestor of the Kent virus infected the individual and was not immediately destroyed, because the individual may have been immunosuppressed. The virus survived and it mutated, but the virus was not removed and it mutated again and again. Virus can be detected in some individuals for many weeks after symptom onset and there are cases of coronavirus infection being detected over a hundred days. If that person is not aware that they are “virus -central” they may infect others.

If you are immunosuppressed due to your MS treatment and the virus is not removed, it may mutate and you don’t want to be the source of the “Whitechapel Variant” or will it be called the “Cockney”. Now I don’t tell you this to scare you as I am sure that eventually the immune system wins and if you get the vaccine at 12 weeks it is better than none, and for some vaccines may give you a bigger protective response than at 4 weeks. Howver, this, is one good reason why it is valuable to get effective protection, which can be achieved via vaccination, as intended by the manufacturers and to ensure that you socially distance from people, whilst that protection is being formed.

However, bear with us and hopefully the “final”…”final”….”final” advice is the last one….until it changes again:-(.

P.S. ProfB went under cover at UK Joint Committee Vaccine and Immunization (JCVI) meeting, he shaved his head, got some lipo suction, got some trendy square glassess from his grandad and a fake 70s Porn star Tash to scanning peoples thoughts about their vaccination advice strategy….Guess what happened.

P.S. Don’t watch this. If you can’t stand a bit of Gore.

And to finish on a happy note

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MouseDoctor

14 comments

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  • Do you think that the government will eventually accept that the Pfizer vaccine second dose needs to be given by 8 weeks at the latest?
    If you have MS and I’m not on a DMT I’m worried that 12 weeks between the vaccine will make the vaccine worthless
    Am I right that the correct spacing is only being applied to people with MS on DMT?

    • For oxford vaccine there is already data that the longer you wait the better it is e.g. dose one 8,000 dose two 22,000 (less than 6 weeks), 22,000 (6-8 weeks), 36,000 (9-11 weeks), 65,000 (more than 12 weeks. There will be enough tier two health care workers on the pfizer that have had the jab in decemeber that are waiting for Jab two e.f ProfK is now 7 weeks, they will be checking the bloods to see what happens so by the time teir 6 (all of MS. start I guess in a couple of weeks) comes around they will know within 4 weeks of you jab happens in thousands of people so fear not ProfK and Co is you guinea pig, But remember one dose and 3 weeks and you are over 90% protected. It is rather unthinkable that the antibody level will drop that quick as it takes one month for half of it to do. Generally the lower you wait between vaccine doses the bigger the booster effect.

      • I had my first dose of Pfizer 1.5 week ago as I am in group 4 and have been told to call my GP in 4 weeks so I’m unsure whether to push for the second dose sooner rather than later especially if it is going to be proven that a longer gap between Vaccines gives a better result after all.

        • In terms of the BartMS, the dosing recommendations were created by information we have from Barts Health recomemdation that decided to follow the green book and not he JCVI. This is based on the green book V6. V1 was in November. In terms GP it depends if they have read this. In terms of 2 doses at 4 weeks the results are about 99.98% protection based on israeli data. You are not going to get much better than that so why delay. Off one dose 90% protection but no information past 3 weeks. If you look at most vaccines you get a long gap between doses. However this dosing regime was developed for a quick completion. The moderna vaccine gives 3 times more RNA it give maximal antibody response of one dose. I believe our nurses are contacting people.

          Based on the trial the recomended and designed dose interval as 3 weeks with no-one being over 6 weeks. For the Zeneca people in trial had up to a 26 week gap.

          • I will try and push for the second vaccine as soon as possible but from what I am hearing people are still being given a slot 12 weeks apart from the first one
            Something I wish the government had done but which I bet they have not is calculate how many Pfizer vaccinations they have and allocate two of them to every person so they know how many people they can vaccinate while still promising them their second dose. I worry that they have simply administered dose one of Pfizer until the the stock is exhausted and will then have to wait to get more vaccinations to start on the second round.
            Is that an unfair assumption?

          • I suspect you are right, the next batch was due March I think, but I think they are no storing second doses

  • Our area is already into groups 5 and 6 which is why I received my initial Pfizer dose on Friday. I was presented with a card saying my second dose will be administered on the 30th April.
    I am concerned that the 12 week gap + a blunted immune response will mean I am at risk of inadvertently infecting others or being the source of Kent II – yes I do reside here🤦🏻‍♀️

    • You wont do this because you are thinking about other people and therefore you will avoid those situations where you will infect other people and where you will be infected, exclusions seem to apply e.g. Joggers and others. The maximum effect after pfizer is 7 days after the boost so be expecially careful like you have been for the past year. What I wrote is hypothectical. Kent II wont have your name in it unlike some of the reagents that DrAngry makes he puts in his initials ASK = Alaline serine lysine in the amino acid sequence.

      If you get infected it would be interesting to see how long you are infected I know of cases of people being positive for many weeks. If you are a health care worker you may get access to getting tested twice weekly. If you havent got the virus there is nothing to mutate. If you feel like had the virus get tested. This can be done online and is sent in the post. They email test the results back. I live in one of the South African areas and did one it is easy. So if concerned you are infected get one, then get another one so see how long it lasts. Your immune system will get rid of it. But if you are positive you need to isolate.

      Remember the person who got infected whilsts having alemtuzumab, they had no T or B cells and got rid of the virus in a week and made an anti-COVID-antibody response

      • Thanks for the reassurance MD.
        I’m not a health worker nor do I head out much, so my risk of infection is mostly from hubby, if he were to become infected.
        Hope everyone who has the vaccine doesn’t become cavalier about maintaining all the social distancing measures – as you say I’ve been careful and intend to stay this way, 🤞others do too!

        • Do you have a plan if he gets infected, we split the house/rooms in two, luckily we have a spare bedroom and two toilets but you can still distance. Maybe a good chance to get total control of the tele:-)

  • talking of first doses
    If some got the first dose and then 3 weeks and 5 days later gets, say, Ocrevous, again, will there have been any benefit in having the first dose?

    • Ocrelizumab has a tiny impact of CD4 and CD8 cells and there the cells that help antibody production, macrophages and anti-Viral T cells should be OK. The first dose makes antibody producing cells This will happen been 6-14days and these do not express CD20 and therefore will not be killed by the ocrelizumab so it should not wipe them out. However we will only know when we do it.

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