Research shows blood cancer patients generate strong T cell immunity after SARS-CoV-2 vaccination

[CLLerinOz]

Today, the Doherty Institute in Melbourne, Australia, released a statement about a research study that shows that blood cancer patients highly benefit from COVID-19 vaccinations which boost their levels of T cells, irrespective of their B-cell numbers and antibody response.

It found that "despite being heavily immunocompromised, haematology patients generate strong cellular immune responses against SARS-CoV-2 after vaccination, on par with that of healthy individuals."

The research is available as a journal pre-proof in Cell Reports Medicine today. A large team of collaborators worked on the study led by Professor Katherine Kedzierska, including a number of CLL clinicians and researchers.

The Doherty Institute says this is "the most comprehensive analysis of adaptive SARS-CoV-2 immunity to date in haematology patients of varying diseases and treatments across three doses of COVID-19 vaccination in comparison to healthy individuals."

"University of Melbourne Dr Oanh Nguyen, Senior Research Fellow at the Doherty Institute and co-lead author of the paper, says it is important to really understand vaccine efficacy in this immunosuppressed high-risk group of patients to help prevent severe SARS-CoV-2 infection.

“This group is at high risk of viral infectious diseases, such as influenza and SARS-CoV-2, and yet they are not always included in pre-clinical trials that test vaccine efficacy,” Dr Nguyen says.

“Our study shows that they highly benefit from receiving three doses of vaccination. The vaccines boost their levels of T cells, the white blood cells that kill viral infected cells, irrespective of the patient’s B-cell numbers and antibody response."

“We also looked at the characteristics of these T cells that are generated after vaccination, and we found that these signatures are very similar to healthy individuals that are either infected or vaccinated. These findings are really important and super exciting for cancer patients,” Dr Nguyen adds.

“What we have shown is that people with co-morbidities that have a heavily impacted B cell immune arm, can have an mRNA vaccine to elicit T cells and give them that extra level of protection,” Professor Kedzierska says.

Associate Professor Teh says this research is important for clinicians working with blood cancer patients.

“Clinicians can be confident that it is safe and beneficial for their patients, who are heavily immunocompromised and vulnerable to severe COVID-19 infection, to receive vaccination against SARS-CoV-2. Regardless of their diseases and treatments, COVID-19 vaccination generates strong T cell immunity in this group,” Associate Professor Teh says."

doherty.edu.au/news-events/...

Nguyen, T.H.O, Rowntree, L.C, Allen, L.F, Chua, B.Y, Kedzierski, L., Lim,C., Lasica, M., Tennakoon, G.S., Saunders, N.R, Crane, M., Chee, L., Seymour, J.F, Anderson, M.A., Whitechurch, A., Clemens, E.B., Zhang, W., Chang, S.Y., Habel, J.R, Jia, X., McQuilten, H.A, Minervina, A.A, Pogorelyy, M.V, Chaurasia, P., Petersen, J., Menon, T., Hensen, L., Neil, J., Mordant, F.L, Tan, H.-X., Cabug, A.F, Wheatley, A.K, Kent, S.J, Subbarao, K., Karapanagiotidis, T., Huang, H., Vo, L.K, Cain, N.L, Nicholson, S., Krammer, F., Gibney, G., James, F., Trevillyan, J.M, Trubiano, J.A, Mitchell, J., Christensen, B., Bond, K.A, Williamson, D.A, Rossjohn, J., Crawford, J.C., Thomas, P.G, Thursky, K.A, Slavin, M.A, Tam, C.S, Teh, B.W, Kedzierska, K., Robust SARS-CoV-2 T cell responses with commonTCRαβ motifs towards COVID-19 vaccines in haematological malignancy patients impacting B cell immunity, Cell Reports Medicine (2023), doi: doi.org/10.1016/j.xcrm.2023....

(my emphasis)

[terryI_uk]

Thanks CLLerinOz, that's some good news to brighten the day. After 6 vaccines I hope I can start to live a more normal life! , Terry

[CLLerinOz Administrator in reply to terryI_uk]

It's not as good as getting the B-cell and T-cell boost that healthy people might get so there's still a need to exercise some caution. However, it's very encouraging news and reassuring to read that we get such strong T-cell immunity after vaccination

[Eucalyptus22]

This is good news but it would be good to get some anecdotal evidence from CLLers on this site about how well they did/or did not do on getting Covid and having been vaccinated and boosted.

I can remember having a conversation with my CNS who told me T cell response after vaccine was good but then couldn't explain why so many blood cancer patients were still dying. Admittedly that was a year ago and things might have improved since then.

[CLLerinOz Administrator in reply to Eucalyptus22]

The story is still a complex and nuanced one and members here have shared a range of experiences, from mild to severe including a few who've recently been hospitalised. However, CLL specialists have reported that now they're not seeing the extremely high level of mortality in their patients that marked the early part of the pandemic and they attribute much of the improvement to vaccinations and antivirals.

Paxlovid wasn't approved in the UK until very late in 2021 and uptake was difficult and slow so it's possible that it wasn't having such a great impact on reducing mortality at the time you spoke to your CNS if it was in early 2022.

Because there's such variance in the severity of the disease, as well as being vaccinated, it's still worth following common-sense precautions like wearing a mask in particular settings and practising safe distancing and air quality measures where possible to reduce the risk of infection and severe illness. It's also important to access treatment as soon as possible after experiencing symptoms or testing positive for COVID-19.

The idea that we can achieve a good T-cell response from vaccination is very encouraging though

[Jm954 Administrator]

Good news but I'm surprised that it's so strong given that we know that T cell exhaustion is common in CLL

Jackie

[SofiaDeo in reply to Jm954]

Since we are about 1/3 of all leukemias, I wonder if the inability to make certain subsets stimulates other subsets like T cells? And that even if our T cell numbers are decreased, the vaccines stimulate the few we have to produce until our blood says "ok, we have the concentration we want". The body will try to reach homeostasis, even if there are fewer cells around to get us there.

Another plug for "extra nutrition and hydration". If we have fewer "good" regulatory cells, they will be working overtime attempting to stabilize body processes.

[Jetliz]

Wow very interesting and positive! Wish I was fit enough to do a cartwheel it's always so encouraging to read this kind of research thank you

[Skyshark]

Can't get a 3rd shot of my primary vaccine in UK. It was Astrazeneca and they haven't bought any for over 6 months. Was diagnosed in Nov 22.

[CLLerinOz Administrator in reply to Skyshark]

Don't worry about trying to access the same brand of vaccine. It's more important to get vaccinated when you're eligible. Many of us have 'mixed and matched' the brands for our primary course and subsequent doses without any problems. For example, in Australia, my primary course was 2 x AstraZeneca and 1 x Moderna. Since then, I've also received 1 x Pfizer and 1 x Moderna and, with a bit of luck, I'll get a Moderna bivalent next week.

[bennevisplace in reply to Skyshark]

Do contact your GP and get your Covid booster ASAP. If you've missed the winter slot they will fit you in anyway.

[Nama-8]

Good news, especially because I really dislike the vaccines. I spend 24 hours in bed desperately ill. Often I feel like there's not much point.

[bennevisplace in reply to Nama-8]

On the contrary, this research demonstrates a good reason to get vaccinated. Even if you have CLL and are unlikely to make many antibodies, your stronger T cell response will mitigate symptoms if you catch the virus.

[Unglorious]

Does this good news re: T-cell also benefit those of us that are on BTK inhibitor treatment? e.g. Aclabrutinib.

[CLLerinOz Administrator in reply to Unglorious]

Yes. The study looked at patients across a range of diseases on a range of treatments and it found that: "Following 3-dose COVID-19 vaccination, haematology patients of varying disease  and immunosuppressive treatments, including those with B cell deficiencies, can still  generate robust and functional spike-specific T cell responses."

Of the CLL patients in the study, some were treatment-naive, some were on a venetoclax-based treatment and some were taking the BTK inhibitor zanubrutinib. Supplementary Figure S12 in the study paper details Individual patient’s immune response following COVID-19 vaccination.

The authors note that: "Larger prospective studies are needed to demonstrate protection against severe and fatal disease with patient stratification based on antibody/B cell and T cell responses".

[Unglorious]

As per usual, thank you so much for your response.

[Fran57]

Thanks so much for that… it really sounds like very hopeful news.

Take care,

Fran 😉

[skipro]

thanks for the article

I’ve searched all over the world for a lab to test T cell function ( not just a number of cells but actual function) against COVID after vaccination. One was in Germany and only checked CD 4 T cells which don’t help ClLers

I found one that test all T cell functions but was accessible only in clinical trial and they would not release individuals their results

Do you have the original article?

Did they say how long the T cells remained active

Do they outline the types of T cells

Eg

CD 4 T cells normally signal B cells to make antibody so CD 4 T cell function doesn’t help us much cuz our B cells don’t work so well

CD 8 T cells directly kill things like COVID

T memory cells can start up a quick response after re-exposure

Thx

⛷️

[CLLerinOz Administrator in reply to skipro]

Hi skipro

There's a link to the journal pre-proof article at the end of the post above and that article contains full details of the study including many figures and supplementary tables of information.

Both CD4+ and CD8+ T-cells were analysed during the study: "Heparinised peripheral blood and serum were collected prior to vaccination (T1), ~1 week following the first dose (T2, optional bleed), just prior to the second dose (T3), ~1 week following the second dose (T4, optional bleed), and ~1 month (T5) following the second dose."

"Additionally, a subset of patients were bled prior to receiving a third dose of BNT162b2 Comirnaty or mRNA-1273 (T6), 1 month following the third dose (T7) and 3-4 months following the third dose (T8). Healthy vaccinated adults were recruited as controls."

I'm not surprised you haven't been able to access this sort of test. The assays used for this research aren't currently available outside of the most advanced research settings and are only accessible in the context of a study/clinical trial like this one or the LLS T-cell study: lls.org/news/study-leukemia....

[skipro in reply to CLLerinOz]

Thanks for the info. I've downloaded it and am eager to review.

I just started V + O and wondering if getting another bivalent booster when the FDA approves it for 65 and older would work while I'm in treatment.

Thx

skipro

[CLLerinOz Administrator in reply to skipro]

Great question, skipro. AussieNeil may be able to help you more than I can on this one.

From my unscientific perspective, I think it could very well put boosters back into the mix for patients who are on treatment with venetoclax and obinutuzumab and also, perhaps, earlier than has previously been advised for those who have completed that treatment, depending on when they've previously been vaccinated. More research will be needed and the LLS study will help us learn more, too, no doubt.

[skipro in reply to CLLerinOz]

thank you

[AussieNeil Partner Administrator in reply to skipro]

Hi Skipro,

As CLLerinOz notes, this new research puts boosters back into consideration when we are in treatment, because it shows that cellular T cell immunity is better than we anticipated. Given V+O isn't going to make much difference to your T cells or your memory B cells for that matter, having a booster is likely to provide an overall reward benefit that is likely to be much more significant than previously thought was the case.

One silver lining of this pandemic, is that we've learned so much more about our immune system's response to new(ish) viruses, but we've also highlighted how much we still don't know. The challenge is that we have lots of tools for antibody research and we can easily measure antibodies as they free-float in the blood. T cell changes over time are much harder to assess, as you have to somehow track changes in T cell receptor expression by finding and sequencing T cell DNA. Even small teams can do B cell related research, but it takes some serious funding and a knowledgeable, well established team to do T cell research. A least with CLL being the most common adult leukaemia/lymphoma, we are seeing some research.

Neil