Vaccine readiness and CD20 depletion. Will you get a 2-4-1 solution from the manufacturer’s?

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We have been taking about mushroom hunting during COVID-19 lockdown and one of the readers pointed out that mushrooms where like disease modifing drugs in their side effects and the need to understand them, so you can make the best choices. But have we been DMT hunting too?

If you are taking CD20 depleting antibodies such as rituximab and ocrelizumab then you make have persistent B cell depletion, which inhibits your capacity to make an anti-vaccine response.

So will you be “vaccine ready” for SARS-CoV-2? Does it matter?

It is clear that some people treated with CD20 depleting antibodies do not make an anti-SARS Cov-2 antibody response, but it is not clear whether lack of this will stop re-infection.

Importantly we can say that some people treated with anti-CD20 produce antibody responses

Meca-Lallana V, Aguirre C, Beatrizdel Río, Cardeñoso L, Alarcon T, Vivancos J. COVID-19 in 7 multiple sclerosis patients in treatment with ANTI-CD20 therapies. Mult Scler Relat Disord. 2020 Jun 15;44:102306. doi: 10.1016/j.msard.2020.102306

Wurm H, Attfield K, Iversen AK, Gold R, Fugger L, Haghikia A. Recovery from COVID-19 in a B-cell-depleted multiple sclerosis patient. Mult Scler. 2020 Sep;26(10):1261-1264

Maillart E, Papeix C, Lubetzki C, Roux T, Pourcher V, Louapre C. Beyond COVID-19: DO MS/NMO-SD patients treated with anti-CD20 therapies develop SARS-CoV2 antibodies? Mult Scler Relat Disord. 2020 Sep 3;46:102482.

‘It is not totally clear if you can do without the B cells response to deal with COVID-19, although it is clearly evident that you can recovery from COVID-19 if you lack B cells and if you have been treated with anti-CD20. But immunology 101 says that if you have high levels of antibodies that can neutralize binding of the SARS-CoV-2 virus to its target ACE2, then you can inhibit infection.

We know this is the case because if you take blood plasma from someone who has recovered from COVID-19 and inject it into some one who is severely affected it gets rid of circulating virus. This is called convalescent sera.

Monkey snatches the COVID19 blood samples in Meerut

What is this? If you remember the film “outbreak” with Dustbin Hoffman. A deadly virus came from a foreign country and wa destroying humanity. There was a monkey that was immune so they bled it to get the antiserum to save humanity.

It gets rid of the virus, but does it inhibit COVID-19?

Will it inhibit COVID-19 I susect the answer is probably sometimes. Some people get better when it is used therapeutically but often they do not. Some people argue this is because there may be low levels of antibody in the plasma, or it may be because there are pro-blood clotting effects by the plasma causing harm. It may be simply because it is used too late.

Best way for therapy to work is to give the treatment before you get infected. This is called prophylactic therapy and is the basis of vaccination. So can you bleed enough people enough to treat people before they get the virus.

You don’t need to you can simply make the antibody. You get the protein sequence from someone who has been infected with the virus or a humanised mouse infected with the virus.

You make the antibody and you test to see if the antibody can stop the SARS-CoV-2 virus from infecting cells. This is what loads of labs did. Pharma did it abit quicker, but only big pharma have the infrastructure to to make the antibody in enough quantities to treat the world.

So a company who designed the antibodies has teamed up with the manufacturers of anti-CD20 antibodies to make anti-SARS-COV-2 antibody. They have made high neutralizing IgG1 antibodies. They will be tested in humans…it was also used in (probably Ex-)Pres Trumpster, who got 8 grammes worth so about 13 times the ocrelizumab dose. Whats the cost?,

Will the NHS, NICE approve and use it in severely infected people? However that is is not were the money is, surely it is to produce an alternative to the vaccine. The vaccine costing (who knows) aims to make alot of antibody to block infection. But some people don’t make these antibodies, like some of the asymptomatic people, and people treated with anti-CD20 antibody. You could treat health care workers and 8 grammes of antibody is going to hang around or a long time.

So the manufacturers could give you a Two-for one anti-CD20 and anti-COVID-19 so it wouldnt matter if the vaccine didn’t induce an antibody response. Will they do this? What do you think? It could solve some anxiety

One small problem to this whacky idea…and that is proof that it works. This is not a slam dunk because they are following in the mind set of convalescent sera….same mechanism of action & same trial design = same result?…If that is true it could be tears and convalescent plasma doesn’t always work when given to severely ill people

Trial NCT04425629 is a therapeutic trial design.

Now I know it could be argued that convalescent sera has anti-viral activity and disease worsening capability that is different. But we have to ask are the antibodies deigned for neutralization or something else.

I guess we can ask if the IgG has been silenced because it won’t just be neutralizing the virus. It could kill virally-infected cells by antibody-mediated destruction (complement fixation) or the macrophages can bind to the Fc region (bottom of the antibody) and internalize if making things potentially worse (Antibody mediated macrophage activation syndrome). I am sure they have thought of this:-(. Wonder if they will make an IgA molecule to work at mucosal surfaces?

So they could top up the neutralizing response inhibited and mix it with the anti CD20 give enough of the any

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