It’s behind You!. Again. Alemtuzumab vaccine ready?

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You have heard this before. If you don’t know what you are looking for, you look everywhere and focus on things that are not important.

This is an alemtuzumab study. They do all sorts of studies to see what cells are affected and the conclusion is more “studies are necessary…..to reveal new insights into mechanisms of immunopathogenesis in MS”.

Repopulation of T, B, and NK cells following alemtuzumab treatment in relapsing-remitting multiple sclerosis.Gilmore W, Lund BT, Li P, Levy AM, Kelland EE, Akbari O, Groshen S, Cen SY, Pelletier D, Weiner LP, Javed A, Dunn JE, Traboulsee AL.J Neuroinflammation. 2020;17(1):189. doi: 10.1186/s12974-020-01847-9

But again the focus is on T cells and T regulatory cells and is the the same-old, same-old and sadly they miss an important point. This is that alemtuzumab is COVID vaccine ready.

OK there is no vaccine, but if there was one, alemtuzumab would be ready. To make a vaccine response you have to have new naive B cells.To inhibit MS you have to get rid of memory B cells. So if you can get rid of memory B cells, MS may not come back, but if you have naive cells you can make a vaccine response.

The Naive cells are immature B cells some people call them regulatory B cells

In the case above the memory cells are gone at month 5 in fact they will be gone in week 1 and 75% are still gone 2 years later. However the naive immature B cells, here they are called naive regulatory B cells, are back at 5 months So you have 24-5 = 19 months to get vaccinated. This will allow you to make B cell responses.

Now I have to clarify this abit. Because alemtuzumab depletes CD8 cells, these are the anti-viral cells and they return much more slowly than the B cells.

So what happens with other treatments?

With cladribine we just don’t know because they do not appear to have done a vaccination study! They were so focused on T cells and T regulatory cells in 2010 that they forgot to do…..ok they simply ignored…… the B cell subsets. No wonder people don’t understand how it works!….Come on guys…it’s simples (I’ll do this next week).

Based on what is published we can see that CD8 T cells generally stay within the normal range so not a lot to worry there.

Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis.Comi G, Cook S, Giovannoni G, Rieckmann P, Sørensen PS, Vermersch P, Galazka A, Nolting A, Hicking C, Dangond F.Mult Scler Relat Disord. 2019 Apr;29:168-174. doi: 10.1016/j.msard.2019.01.038.

They show that CD19 B cells are back to normal by 30 weeks after the dose, so within 7 months the vaccination window will be fully open. As you are drug free within a week of cladribine I suspect it will be some time before that when the window opens. So I think alemtuzumab wins the B cell repopulation race and ocrelizumab being depleted forever is at the back of the queue in this respect.

What about the length of the window? With alemtuzumab the memory B cells are gone for at least 18 months-24 months in most people, with cladribine we don’t know….but we know that are gone for at least 12 months and I will guess much longer

Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells.Ceronie B, Jacobs BM, Baker D, Dubuisson N, Mao Z, Ammoscato F, Lock H, Longhurst HJ, Giovannoni G, Schmierer K.J Neurol. 2018 May;265(5):1199-1209.

So thats plenty of time to vaccinate, whilst being protected from MS, but let’s see the real data.

FYI. I believe that ProfK has woken them up to.

The makers of cladribine are doing a study to look at B cell subsets, but let’s take a bet that they will be so interested in mixing the data with the T cell stuff that the B cell stuff will be buried in “the secret is in the balance of the regulation ollocks” and so know one will know how cladribine works! Will the investigators have the Jajce (hint this is Slovene for eggs) to ditch the T cell stuff that we already know about and put the B cell data centre-stage. I doubt it….but let’s see.

So we have one more depleting agent to look at and that is ocrelizumab.

Here you keep B cells gone forever, so the vaccine response will be inhibited, but this needs a post on its own to look at the vaccination window. No that’s the B cells

I would say to some large extent, there should be no worries about T cells….unless you are a T cell biologist. This because if some really believe that ocrelizumab works because it depletes (CD8) T cells…….Yer right.

Are those few cells that are gone, responsible for MS and control of SARS-CoV-2 responses? However, if you are willing to accept the unplausible whilst rejecting the simple view ocrelizumab works because it depletes B cell subsets, it seems that you head is fixed and you are not capable of looking behind you, in which case whilst you focus you attention on the witches black cat, the Nasty big Cat is going to get you, because you don’t know where to look!

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