We have made the suggestion that vaccine response relates to the B cell numbers but this is related to the presence of depleting antibody so you could measure that instead, This is a study with ocrelizumab but this conclusion has been seen before with rituximab
Toorop AA, Hogenboom L, Bloem K, Kocyigit M, Commandeur NWM, Wijnants A, Lissenberg-Witte BI, Strijbis EMM, Uitdehaag BMJ, Rispens T, Killestein J, van Kempen ZLE. Ocrelizumab concentration and antidrug antibodies are associated with B-cell count in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2023 Jan 24:jnnp-2022-330793
Background: The majority of patients with multiple sclerosis on ocrelizumab have B-cell depletion after standard interval dosing of 26 weeks. With B-cell-guided dosing patients receive their next dose when B-cell repopulation occurs. Prediction of B-cell repopulation using ocrelizumab concentrations could aid in personalising treatment regimes. The objectives of this study were to evaluate the association between ocrelizumab drug concentration, antidrug antibodies (ADAs) and CD19 B-cell count, and to define a cut-off ocrelizumab concentration for start of B-cell repopulation (defined by ≥10 CD19+ B cells/µL).
Results: A total of 452 blood samples from 72 patients were analysed. Ocrelizumab concentrations were detectable up until 53.3 weeks after last infusion and ranged between <0.0025 and 204 µg/mL after 1-67 weeks. Ocrelizumab concentration was negatively associated with B-cell count, with body mass index identified as effect modifier. We found a cut-off value of 0.06 µg/mL for start of B-cell repopulation of ≥10 cells/µL. Ocrelizumab ADAs were detectable in four patients (5.7%) with corresponding low ocrelizumab concentrations and start of B-cell repopulation.
Conclusions: Serum ocrelizumab concentration was strongly associated with B-cell count. Measurement of ocrelizumab drug concentrations and ADAs could play an important role to further personalise treatment and predict the start of B-cell repopulation.
What about t cells?
Vaccine responses are a mix b an t cells responses
Maybe even nk cells
CD20 depleting antibodies dont really affect T cells so no need to think about that:-)
Would you expect development of anti-drug antibodies to affect efficacy of anti-CD20 therapies over time or would you expect the B cell depleting effect to prevent a neutralising anti-body response?
I’d guess that it would depending on therapy concentration and B cell levels. Given MS treatments aim for very low B cell numbers I wouldn’t expect a significant anti-drug antibody response
For rituximab they can occur in up to 35% of people but with continuous treatment itmay be lower for ocrelizumab its about 1% I have seen paper up to 5% of people for ofatumumab the ADA is apparently low.These antibodies will protect against making ADA
Could EID increase risk of ADA because of lower drug concentration over time?
Yes good idea….I believe it is a possibility I have mentioned this some posts previously but it is a hypothesis we need data
see this post
Good logic…ADA can develop in people on CD20 antibodies but people get protected by the biology of B cell depletion
Pharma to the rescue 🙂
Initially, T-helper cells secrete chemical messages that summon the key arms of the immune response:
Cytotoxic T-cells recognize and kill virally-infected cells, an important part of the early elimination of the virus.
B-cells produce virus-specific antibodies, which can neutralize the virus and mark it for destruction. If we’re exposed to the virus in the future, these antibodies can potentially protect us in two ways: They prevent the virus from entering our cells and they mark viruses and virus-infected cells for other immune cells to come in and destroy them. The level of these antibodies circulating in the body declines over time.
The persistence of memory
Another critical component of vaccination is that it helps produce memory B- and T-cells that are specific to the virus. Like an army reserve force, these immune cells can be quickly activated in the future to produce antibodies to stop the virus from invading your body. And unlike antibodies, these cells persist. “Once you stimulate memory cells for a particular antigen, they can remain with you for life,” says Gruber. For some pathogens, however, memory cells can be short-lived.
So with extended interval dosing anti-CD20 drugs will this lead to higher ADA’s in patients thereby rendering that drug less/not effective? I’m EID ocrelizumab (12 month between doses) and this would be my only concern, otherwise I’m all for it.
A possibility. I have mentioned this
see this post