SARS-CoV-2 mRNA vaccination exposes progressive adaptive immune dysfunction in patients with chronic lymphocytic leukemia

[zaax]

ncbi.nlm.nih.gov/pmc/articl....

[AussieNeil Partner Administrator]

Very interesting paper, though you've referenced the preprint from December 2022. Good to see that Pubmed references the subsequent peer reviewed version of this study from June 2023.

ncbi.nlm.nih.gov/pmc/articl...

Much of what is covered in this paper was already known, though it's good to see additional details. (We struggle to produce neutralising antibodies after vaccination and while our T cell immune response is much, much better, it's still not as good as that seen in controls.) However, I don't recall seeing the difference in response between the BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna) antibody responses published beforehand. I'm pleased that I went with the Moderna shots, given the "CLL patients who received mRNA-1273 had 12-fold higher (p < 0.001) NAb titers and 1.7-fold higher (6.5, 95% CI 1.3 to 32, p = 0.02) response rates than BNT162b2 vaccinees despite similar disease characteristics.". Hence the conclusion "higher NAb titers and response rates identify mRNA-1273 as a superior vaccine for CLL patients".

It was also interesting to have confirmed that "CLL pathogenesis is characterized by a progressive loss of adaptive immune functions, including in most treatment-naïve patients, with preexisting memory being preserved longer than the capacity to mount responses to new antigens." (My emphasis) That validates the regularly given recommendation to get up to date with vaccinations as soon as we are diagnosed. healthunlocked.com/cllsuppo...

Neil

[Spark_Plug in reply to AussieNeil]

This may be considered older information due to so many papers produced since COVID -19 mNRA vaccines were rolled out but as far as I could tell this possible explanation is still repeated. But as of this articles reporting, a new paper published May 11, 2023.

Thus, boosters are important for all people age 60+, but are especially important for Pfizer vaccines. A possible reason for this difference between vaccines is that the Moderna dose is much higher than the Pfizer dose (100 μg versus 30 μg). Older bodies may need the bigger kick from the larger Moderna dose to prime their immune systems. [my emphasis]

news.northwestern.edu/stori...

Simply put, I think that dosage is a variable that should be not ignored when when discussing efficacy or the after affect response that is sometimes reported on this forum.

It is not lost on me that Gen X have had a tendency to be more Brand loyal as a group, so starting with Pfizer, held that course in the past. Last year I experimented with the roll out booster being Moderna, and finished with two Pfizer for the rest of the year.

I plan to follow that pattern for me [personally] this year as well. It saw us through last year when my wife contracted COVID. Not discounting very strict protocol, I did remain unscathed. My time frame is November, March, and July for the year. I'm anticipating the seasonal holidays, spring break, and summer vacationing. This works for me in the Northern Hemisphere, where you are may be quite different, so plan accordingly.

[Zia2 in reply to AussieNeil]

I’ve always taken the Moderna as well. What are your thoughts on the newest vaccine (that I believe will be available soon)?

[AussieNeil Partner Administrator in reply to Zia2]

I haven't looked into the differences, as the Moderna COVID-19 vaccine won't be available in Australia until at least April next year

[Zia2 in reply to AussieNeil]

Sorry to read that

[SeymourB]

zaax -

Reading the highlighted text, my brain inferred additional meanings that were hopefully not intended by the author. I guess I'm a knee-jerk debunker at this point.

"Multiple reports indicate diminished immune responses in CLL patients following COVID-19 mRNA vaccination, [24–26] but the reasons for this decreased reactivity even in treatment-naïve patients remain largely unknown."

Without reading the rest of the paper, at first, my brain wondered, "Are they saying that the vaccination further suppressed immune response in CLL patients?" It might be clear to some that that is not the case, but there's much documented about actual SARS-CoV-2 infections suppressing immunity in various ways, which caused the actual initial inflammation and acute breathing response problems that killed so many. I've seen no evidence that the vaccines do this, however, despite fervent attempts by antivaxxers to allege all manner of evils happening to huge numbers of people caused by (and not just following) the shots.

Another thing my brain reflexively wondered, "Are they saying this happens only with mRNA vaccines and not vaccines that work by other methods?" Again, I've seen no evidence of that.

I guess I'm just too defensively since my second COVID infection. This time, I'm doing better. My first was before treatment, and a week after a dose of Evusheld. This time, it's post treatment, and a week after my second dose of IVIG. Each time, I think the vector has been my wife, who teaches 7th and 8th grade, reacting perhaps overconfidently, and letting down her guard near an infected person.

I will mention that I participated in the Leukemia & Lymphoma Society's COVID vaccine study. I was tested before each vaccination, and then again 6 to 8 weeks afterward. Even in W&W, I made few detectable spike antibodies in response. Now I'm on IVIG to cloud the test results further, but I think I'll do one tomorrow since it's inexpensive (US $69 at LabCorp), even if insurance doesn't cover it. But insurance always has in the past.

The paper, however, does seem to rather cluelessly allege, "the reasons for this decreased reactivity even in treatment-naïve patients remain largely unknown." This is something that has been and continues to be explored. There's so many moving parts to immune function and dysfunction, and much has been documented. What they can't seem to be able to say is why person X will respond to vaccines just fine, while person Y will not. So we're left to assume that we are immunocompromised - which many of us, even in W&W are indeed, based on increased diagnosis and treatment of infections alone. It's not even the FiSH type, IGHV mutation status, lymphocyte count, nodes, or spleen. The best that can be said is that if you're immune compromised now during W&W, it's going to get worse before treatment. Recovery after treatment is hard to predict, too.

I would also caution readers against accepting "sero-conversion" as some sort of binary victory goal in vaccinations. Sero-conversion can be declared if you make a single detectable antibody. It not at all the same thing as the much harder goal of attaining a "correlate of protection." Failing to sero-convert is an abysmal failure, and indicates a severe immunocompromise. The correlates of protection have been a continuously moving target, and expose how much of immunology is simply unknown so far.

I'm looking forward to hear what Jacob Soumerai, MD, Department of Hematology and Medical Oncology, Mass General Cancer Center, Boston, Massachusetts will be saying about the subject on an upcoming CLL Society Zoom:

cllsociety.org/2024/07/immu...

They will surely post the webinar on their YouTube channel. Do try to subscribe and if you like one, them a thumbs up to show you watched it and liked it.

youtube.com/@cllsociety/videos

Soumerai has done several papers on immune dysfunction and recovery. Wish I could say that he's clearly proven that a liquid fruit and veg cocktail gets us back into stronger immunity without boosting our CLL. Well, he might, and from him I'd give it more credence before trying. But I don't expect anything quite that dramatic, or we'd have heard much about it from all quarters.

=seymour=

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References:

In addition to the 3 articles cited in the original artical in the post (referrences 24, 25, and 26), here are more:

ncbi.nlm.nih.gov/pmc/articl...

Humoral and cellular immunogenicity of SARS-CoV-2 vaccines in chronic lymphocytic leukemia: a prospective cohort study

Blood Adv. 2022 Mar 22; 6(6): 1671–1683.

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ashpublications.org/bloodad...

IgG testing, immunoglobulin replacement therapy, and infection outcomes in patients with CLL or NHL: real-world evidence

Blood Adv (2024) 8 (16): 4239–4249.

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ncbi.nlm.nih.gov/pmc/articl...

The impact of anti-CD20-based therapy on hypogammaglobulinemia in patients with follicular lymphoma

Leuk Lymphoma. 2022 Mar; 63(3): 573–582.

Has info that pertains to us as well.

[RosettaClapp in reply to SeymourB]

I thought we are ALL immunocompromised to a degree and this is what my consultant has told me time and time again.. Am I wrong is this assumption?

[SeymourB in reply to RosettaClapp]

RosettaClapp -

We are indeed all immunocompromised to a degree. It's not a binary thing at all, though,

The extent of immunocompromise varies considerably between patients with otherwise identical markers, and there's not very good ways to measure it aside from vaccine titer testing.

Vaccine titer testing exercises multiple aspects of the immune system to ultimately produce antibodies. It's fairly inexpensive, requiring 2 blood draws for the antibody tests, the vaccination itself. But it does not quantify T-cell immunity.

Ultimately, we want to know if we're the unusual sort of CLL patient that can safely eat in a crowded restaurant without masking, and whether we're the sort who really should consider a visit to the emergency department at a particular temperature. Physicians need this info, too. They tend to lump us either with the general public, or admit us to hospital to be safe - where we actually might get exposed to worse pathogens.

Eric Topol recently blogged on the idea of better immune testing:

erictopol.substack.com/p/wh...

=seymour=