Depleting Memory B cells doesn’t get rid of your antibody response

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If you get vaccinated are MS drugs going to get rid of the anti-vaccine response and they should get rid of memory B cells to inhibit MS what about the SARS-Cov-2 response? Will it stop that ….Probably not. This is suggested from studies in monkeys

Hammarlund et al. Plasma cell survival in the absence of B cell memory Nature Communications 8: 1781 (2017) 

The question of plasma cell longevity and its role in maintaining serum antibody levels has sparked considerable debate. Studies in mice demonstrated that long-lived plasma (antibody making cells) cells could survive for over a year in the absence of memory B cells induced by irradiation. However antigen-specific serum antibody declined compared to those of untreated controls.

To investigate this question in more detail, it was shown that naturally acquired and vaccine-mediated immune responses in rhesus monkeys that persist up to a decade after immunization, demonstrate the existence of long-lived plasma cells that can independently maintain serum antibody levels for many years in the absence of memory B cells.

Antibody decay rates were measured during the first month after each booster vaccination and found to have an antibody half-life of 19–21 days, similar to the decay rate of IgG molecules themselves. This indicates that most of the antibody-secreting cells (ASC) induced early after vaccination are very short-lived. From 1 to 6 months after the last vaccination the estimated antibody half-life increased to 62 days. This is in contrast to the more stable tetanus (lockjaw)-specific antibody half-life of 1390 days observed from 6 to 12 months after final vaccination (i.e., 9–15 months after primary vaccination).

At 1.5 years after primary vaccination, 4 experimental animals had CD20+ memory B cells depleted by the intravenous administration of 3 weekly doses of anti-CD20 antibody. Early analysis of antibody decay rates after memory B cell depletion indicated an average tetanus-specific antibody half-life of 2.3 years

However, studies in humans indicate that anti-CD20 depletion may not be as effective at removing B-cells from lymphoid tissues as it is for depleting B cells from the circulation. To reducethis potential caveat, the spleen and inguinal lymph nodes (i.e., the draining lymph nodes after vaccination in the quadriceps muscle) were surgically removed from the experimental animals at ~3.5 years after primary vaccination and intravenous anti-CD20 depletion was repeated.

Tetanus-specific B cell memory is long-lived in rhesus macaques but after anti-CD20 depletion and immune reconstitution of the general B-cell repertoire, tetanus-specific memory B-cells remained below detection when examined at 2.5 months or even 2 years later. The tetanus-specific antibody half-life observed among the experimental memory B cell-depleted animals (T 1/2  = 6.1 years, range; 4.7–8.2 years) 

Altogether, this indicates that after surgically removing potential B cell reservoirs from solid tissues such as the spleen and the draining lymph nodes, as well as all detectable tetanus-specific memory B cells from the circulation, tetanus-specific serum antibody titres continued to be maintained above the protective threshold for the lifespan of the immune host. Importaant some that took up a dye ten years earlier can still be found, showing that they survive for a long long time….meaning so will you anti-COVID-19 response.

But whats important T or B cells?

Extended interval BNT162b2 vaccination enhances peak antibody generation in older peopleParry, H. M., Bruton, R., Stephens, C., Brown, K., Amirthalingam, G., Hallis, B., Otter, A., Zuo, J., Moss, P.10.1101/2021.05.15.21257017 — Posted: 2021-05-17

Abstract Objectives: To assess the relative immunogenicity of standard or extended interval BNT162b2 vaccination. Design: Population based cohort study comparing immune responses 2 weeks after the second vaccine, with appropriate time-matched samples in participants who received standard or extended interval double vaccination. Setting: Primary care networks, Birmingham, UK. December 2020 to April 2021. Participants: 175 people aged over 80 years of age. All donors received the BNT162b2 Pfizer/BioNTech vaccination and were vaccinated with either a standard 3 week interval between doses or an extended interval schedule. Main outcome measures: Peak quantitative spike-specific antibody and cellular immune responses.

Results: In donors without evidence of previous infection the peak antibody response was 3.5-fold higher in donors who had undergone delayed interval vaccination, but on the down side, Cellular immune responses were 3.6-fold lower. Conclusion: Peak antibody responses after the second BNT162b2 vaccine are markedly enhanced in older people when this is delayed to 12 weeks although cellular responses are lower. Extended interval vaccination may therefore offer the potential to enhance and extend humoral immunity. Further follow up is now required to assess long term immunity and clinical protection.

Antibody responses after vaccination you get a better response after dose 2

Spike-antibody responses following first and second doses of ChAdOx1 and BNT162b2 vaccines by age, gender, and clinical factors – a prospective community cohort study (Virus Watch)Shrotri, M., Fragaszy, E., Geismar, C., Nguyen, V., Beale, S., Braithwaite, I., Byrne, T. E., Fong, W. L. E., Kovar, J., Navaratnam, A. M. D., Patel, P., Rodger, A., Hayward, A. C., Aldridge, R. W.10.1101/2021.05.12.21257102 — Posted: 2021-05-15

So this shows the antibody response following astrazeneca and pfizer is not that great in many people after first dose, but if it is giving high levels of protection it says low anti-body (less than 50 U/ML) levels are sufficient but with the second dose you get a much better response (most arount 250U/ML) for both vaccines

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8 comments

  • Those plasma cells hanging around 10+years is good news for a sars cov 2 response

    Maybe not so good news for pwms and the role they might play in the disease pathogenesis

    Nice post

  • It is curious that we measure half-life and it is well above the biological Half-Life of a man made IgG. Maybe measuring the decrease of specific IgGs in vivo we could extrapolate the size of the plasma cells pool that drive an antibody response. It will need some assumptions and some maths. It could be useful to understand when one person could be defined OCB free based on the decay rate of IgGs in CSF for patients under RTX or ocrelizumab. What do you think MD, could this be feasible?

  • Just take the vaccine and try not to think about the experiment you are now part of.
    But remember the NUREMBERG CODE protects against just such an experiment, the first leagal case was lodged on May 9th 2021.

  • I have been internally debating this topic, as I glance at my first box of Cladribine. Do I delay Clad and get vaccine first or start Clad and get the shot around month five. Excluding all other factors, this post helps. Thank you MD!!

    • Decided to go with the former. First COVID shot scheduled for next Thursday. Also decided to get the shingles shot prior to Clad initiation, which was a challenging since I am not over 50 years old (FDA approval is for >50yrs). Figured better to be safe, given the US has gone from a strong Covid mitigation approach to acting like the pandemic never happened. Too soon!!!!

      • Goodluck Tommyboy. I hope you get all the antibodies! Also glad you got shingles vaccine, I wasn’t able to coordinate my first infusion of Ocrevus with 2 shingles dose timing prior pandemic. And during pandemic, the system wasn’t flexible for timing infusion and vaccine: I got vaccine 2 months post infusion. I’m fearful now. Confusing government messaging led to a visible large shift this week in my area with mask signs removed from storefronts and many people inside stores and in public gatherings without masks, ignoring 6 foot spacing. The governor announced schools will be maskless in fall. I have one minor child in school. The Current American scientific opinion is that immune compromised shouldn’t test antibody levels with qualitative spike antibody test because the level required for protection is unknown. Of course, a zero level would be enough motivation for an immune compromised person to continue to self isolate and self advocate for optimum timing between an infusion and likely anticipated Covid booster. Immune compromised are not incorporated in new normal. All the more reason You made the best choice Tommyboy. Thank you for having this blog. It is the only source that helps me make important decisions about my MS DMT.

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