Vaccination is upon us and there is one question that is on everybodies lips in the MS sphere and that is how much does ocrelizumab blunt the immune response after COVID-19 vaccination? How do you make it Vaccine ready?
In some parts of the world it will be how does rituximab blunt the immune response after covid-19 vaccination. It will be important to see how well vaccination protects against COVID-19 and to what extent people avoids re-infection.
However, it is not the only DMT that may blunt the vaccine response. Fingolimod and siponimod may do this and the cladribine and alemtuzumab could do this too also, until the cells repopulate. However ocrelizumab is the calender boy/girl in the MS COVID vaccine stakes.
We are all doing the same thing and so the truth will soon be out. There will be none of this Nature/Science/Cell unrepeatable cobblers, where you get the first major publication from the MS mega-star for other labs to then start to repeat it. They find they can’t and have to do everything numerous times over. They then spend the next two years trying to refute the original guff paper and by the time enough people say the original paper was rubbish, Mr and Mrs/Ms Teflon, where the “SH1 don’t Stick” has moved onto the next bit of unreproducuble science. However, in COVID world 2020/2021 you now get ten or more papers on the same thing and you don’t have to worry about the self-serving referee, who blocks your publication. It’s out as a pre-print 3 days later and months before any printed peer-reviewed publication arrives. The SH1 is found out and forgotten, almost as soon as it appears.
In terms of information collection. The big question is how is this being done. Well it depends on how the vaccine is given e.g. in UK we have 3-12 weeks between doses and it depends on when this is given relative to DMT dosing and when the DMT dosing is given relative to the vaccine. The schedule seems to depend on what the JCVI is thinking that week. One can guess that the manufacturer of ocrelizumab would wait until 6 weeks after vaccination, as this is their label advice. The rheumatologists use rituximab, and their label is 4 weeks so you will have that. As the moment this is BartsMS preferred time, immunologically you get reponses before this and this why we are being pragmatic about this. Importantly, as the antibody response of Pfizer jab is maximal within one week of booster, I have heard some groups will do vaccinating 1 week after the booster jab. So in 4 weeks you can have the answer. In Israel if they have vaccinated 3,000 people with MS already there will be enough taking an anti-CD20 to get an answer. In the UK is this 4 or 13 weeks. This will mean we are 9-15 weeks behind the Israelis and the American groups if they have vaccine. However some MS Docs got hold of the jab pretty quickly.
There will be loads of groups doing T and B cell responses.
Many of these groups have been handed wads of cash to set this all up. Pharma has been too slow to respond I think, but they will get there.
However, others have the cash. For example government grants could be diverted to COVID work and other groups were core funded by “people with deep pockets” For example Goldmann Sacks. So people can afford to do all sorts of stuff and have the staff to do this. This is no doubt will include single cell sequencing etc, etc. However, it can be very wasteful. I recently saw one more immune blood gene signature They try to convince themselves and others that you can predict the COVID-19 course by a few biomarkers in the blood. They have obviously being reading too many MRI analysis papers as they get convinced that an r value of 0.2-0.4 can predict anything for the individual. This is delusional, but if you talk to the converted, they lap it up. R=correlation coefficient. 0=unrelated and -1 or 1 is correlated and in my view 0.2-0.4 is just rather meaningless). ProfGs run and Kits Swim won’t cover that type of analysis.
By the time we get any funding for such stuff, it will be done by others, who didn’t need to get support and importantly we will have finished vaccinating every one, because that is the important thing and the Team have been super fast in this respect.
One Research Institute has set itself up as a vaccination centre. They spent the early money being a testing centre to got the assays sorted in house. I can see it now. In you come, consent to get bled, T and B cells stuff done, jab done, booster T and B cells stuff done…Paper written. The authors are in bed with the BBC & Nature/science editors…Publication out. Glory days UK. Sadly, they ignore that it has already been done by the Americans, who have even bigger resource.
We will use the technology we have developed to monitor people in our care and tell us how they responded to the vaccine and maybe give us clues if people may needs booster jabs.
Where will the the information surface? What will it find?
For ocrelizumab we will find that the antibody response is blunted in some people. Importantly there hopefully will be enough variantion in the interval between dosing to know how to optimise vaccination response for others. However, the question will be how low does the antibody level have to get to get protection? To know that, you will have to know, if people get infected and maybe the next question is- infected with what? Chinese, Italian, UK, Kent, the Sister of Kent, South African or Brazilian etc?. If people don’t make antibodies and get infected and deal with the virus it says it is the T cells or the Innate immune system. However, we know the adaptive immune system is important to the vaccine-induced protection, because it takes 12-14 days to develop protection. If there was immediate protection from the innate system then there would nto be this time delay.
The big MS labs will be rushing to show that there is a T cell response in the absence of an antibody response. It will make the anti-CD20 manufactures very happy, it will make people taking ocrelizumab and rituzumab happy, but it will make me happy too. (a) Because the pwMS will be happy (b) because if you remember we said that the innate immune response was important and that you can get rid of the virus before a significant B cell response is generated and we said this before we knew anything that was happening, it was based on immunology 101 and reading and was not written after the result was known. Importantly we stuck our neck out for our heads to be chopped off if we got it wrong. I am pleased that we were not far off and the Doomsday scenario envisioned by the Association of British Neurologists did not happen. However (c) I will get an even bigger smile because in trying to prove that there is antigen presentation to make a T cell response to fight COVID-19 after ocrelizumab, they will be undermining their own belief that anti-CD20 works because it block antigen presentation in MS. You can’t have I both ways! I expect there to be a T cell response because it will be driven by dendritic cells.
I have no vested interest that anti-CD20 has to work via antign presentation and if that turns out to be the case it is not a problem for my understanding of B cell involvement in MS. I really hope that people on ocrelizumab do make a T cells response, because it a one in the eye for the dogma machine and it makes me less concerned about people with MS getting COVID-19, if they are treated with ocrelizumab. If there is no T cell response then it can be used to help explain the clinical response.
In reality the people dosing the T and B cell studies in MS, will probably get beaten by the people doing anti-CD20 in other conditions like arthtritis and these will be beaten by people doing cancer studies with T and B cell depleting agents, which have been core funded. Importantly, these studies will not get at the levels of T and B cell responses that are important for vaccination protection. This may best be done by the UK Challenge trials
In these trials they will take healthy 18-30 year old volunteers, who I expect will be given a few bob for their time, who will be vaccinated and then infected with SARS-COV-2. So rather than vaccinating 40,000 people to find 150 who get infected. You simply take 150 people and infect them, job done in a month or so for the fraction of the cost of a 40,000 people trial. Who would do this? There are volunteers. Now you can argue why do this? There are now enough vaccines. However against what variant? The most adaptable vaccine is the RNA vaccine. There is no UK-based RNA vaccine maufacturer. The UK government have lobbed a lot of cash to Collonial College London and they has made a self-replicating RNA vaccine. Collonial College is miles behind those already in use. However, we are going to need to make vaccines against the new variants and new viral threats. The best way to avoid vaccine nationalism is to have your own manufacturing capability . The UK has paid to make a Challenge trial site in London. They are ready to go. You can get you science answers here.
However, to help us look after you, you can sign up to Dr Ruths/DrAngys Antibody study and volunteer to give a drop of your blood, ideally before, and after vaccination. You can email the team firstname.lastname@example.org The team will call to talk to you to explain what we do. ProfG and Kit raised the cash as we got no external support for this, so we can send out the cards to you, there is a paid return envelope there. We have already got over 200 people signed up
Here is a short video of what you have to do from your own home. This was made by one of our students. If you have two cards you only need to fill one card. One-two good drops is all that is needed but if you can give us 5 drops that will be nice.