We are now firmly in vaccine mode and the race is on to determine what are the effects of MS drugs on the vaccine responses. The real world vaccine responses of health care workers and care home people are already published in pre print form and I have to say already been replicated in a number of studies. There are no surprises so far. Although a few people get a late stage injection reactions (a week after injection) with the Moderna vaccine, but this is irrelevant as we haven’t had any of that vaccine yet in the UK. I bet it means the protein made by the RNA is present for over a week and you vaccinate and get an immune responses and then the immune response attacks the vaccine protein still present in the tissue.
As you can see you get an antibody response after the first Pfizer vaccine and it raises abit for the second injection. However, if you have had COVID-19 you are more likely to get a maximal response after the first dose. However, this is not always the case and best protection is after the two doses, unless you get a single shot vaccine.
For people on a twelve week dosing cycle as in the UK, I suspect we will see a deluge of these papers in the next week or three. First the case reports, then a few people and then studies in thousands of people.
However, this is not what we want to know.
Based on what is in the treatment labels from the FDA and EMA, fingolimod and ocrelizumab are the most likely continouously administered agents to blunt the vaccine antibody responses. Although is may be possible that alemtuzumab and clabribine can influence vaccination when cells are depleted, that alemtuzumab can induce anti-drug antibodies in 60-80+% of people within one month of infusion when there is not a T and B cell in sight in the blood suggests that I may be worrying for no reason. It was also clear, based on the ACTRIMS 2021 presentations that vaccine responses occurred in cladribine treated people even when immune-depleted.
However, let’s face it we all know (deep down) that ocrelizumab and rituximab are going to be the problem children as far as MS drugs and vaccinations are concerned. If there are no B cells present and repeatedly depleted, your ability to generate new B cells responses is likely to be curtailed. However, the impact on dosing in relation to time after infusion is going to be key information that we need to know. It could be you make and antibody response and it quickly disappears.
I may be wrong and importantly, even if the levels are curtailed it may be enough to be protective. But what is protective? There is “sterilizing immunity” which means your immune response is so hot that if you get infected then the imune response is so good that you get rid of the virus and you can’t pass it on. However, I suspect that people may get re-infected. The occurence of this is low but it does happen. However, the important point is that you get rid of the virus more quickly if you have immunity to it. You don’t want Long-COVID and this problem hangs around for many months in some people. You get immunity by vaccination.
Immunity may wane with time just like it will in people who are not on a DMT, however even though the antibody responses have waned there is still immunological memory and you will get rid of the virus before it can do too much. . However, I have suggested that you can get rid of the COVID-19 without the need for antibodies.
So the key experiment is going to be what is the T cell response to the vaccines going to be. But one thing I can say is that the T cell response is different to the B cell responses and whilst some people may need higher levels of antibody to get rid of the South African and Brazilians variants, at the T cell level they are all toast. In this study they have taken T cells from people vaccinated with the RNA vaccines to see if the T cell response to the original Chinese variant, the UK variant, the South African variant the Brazilian variant are different. They aren’t. Therefore, if you get infected with the South Africa variant your T cells will deal with it.
What has this got to do with MS?
Will the T cell response be intact or blunted? This will provide insight into how ocrelizumab works in MS. If you can’t make a T cell responses to the vaccine, maybe you can’t you make a T cell response in MS. Likewise if you can then you can and suggests that T cells responses can be generated in MS. If true then it suggests the idea that ocrelizumab works by inhibiting T cells via antigen presentation may be wrong. I hope a CD8 T cell response is made as it will be anti-viral. The beauty of this is we will get the real answer soon as loads of labs will be doing this experiment. As a scientist I look forward to see what happens. Eitherway