Fast, high-throughput methods for measuring the level and duration of protective immune responses to SARS-CoV-2 are needed to anticipate the risk of breakthrough infections. Here we report the development of two quantitative PCR assays for SARS-CoV-2-specific T cell activation. The assays are rapid, internally normalized and probe-based: qTACT requires RNA extraction and dqTACT avoids sample preparation steps. Both assays rely on the quantification of CXCL10 messenger RNA, a chemokine whose expression is strongly correlated with activation of antigen-specific T cells. On restimulation of whole-blood cells with SARS-CoV-2 viral antigens, viral-specific T cells secrete IFN-γ, which stimulates monocytes to produce CXCL10. CXCL10 mRNA can thus serve as a proxy to quantify cellular immunity. Our assays may allow large-scale monitoring of the magnitude and duration of functional T cell immunity to SARS-CoV-2, thus helping to prioritize revaccination strategies in vulnerable populations.
Has someone already posted the article here while I was sleeping?
If it's as the authors present it, I think this is a very big deal - especially for the immunocompromised sub-population, many of whom doubt the protective value and durability of their antibody reponse to vaccination.
I would be grateful for any informed comments on the technology.
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This is a super paper bennevisplace! The technology isn't new, but what the researchers have done is to 1. identify a reliable, easily quantifiable marker ( CXCL10 messenger RNA) for testing of T-cell response to spike protein, and 2. to develop a protocol using appropriate reagents, etc. for quantitation of the marker in whole blood on multiple PCR machines. IE, no special equipment (other than the PCR machine) is needed and the turnaround time is ~24 hr.
bennevisplace and RogerPinner , I contacted the senior author of the paper (Ernesto Guccione, Icahn School of Medicine at Mount Sinai) and received an immediate response to my questions about the timeline for clinical validation, FDA submission and estimated time of approval:His response:
"...thanks for asking and we are indeed gearing up to perform a clinical trial in cancer patients as we speak.
The test has been commercialized to Hyris.
cc-ing Fergal here who can follow up with you with more answers on the timeline."
So, if Fergal responds with more information, I'll let you know!
Bennevisplace, One of the sentences in the article that stood out for me was "Clinical validation of this assay in response to recent draft guidance from the US Food and Drug Administration and European Medicines Agency is ongoing in a Clinical Laboratory Improvement Amendments (CLIA)-certified microbiology laboratory". I'm not sure whether that applied to the whole trial, but my guess is we are still a long way from being offered this test as a matter of routine....which like Evusheld here in the UK, is , to put it mildly, a bloody nuisance.
But medically it's all moving in the right direction. Thanks for the info.
I've seen other studies that use CXCL10 as a proxy for T-cell activity, but not over a long period.
Over a longer period, CXCL10 is not specific for SARS-CoV-2. You could have gotten , say, a flu vaccine, or a different infection. As time goes on, the specificity and reliability of this will fade. So I think it's best used right after vaccine.
By far, the most specific and reliable test of T-cell function is DNA sequencing of T-cell alpha or beta receptors, and comparison to a database. Adaptive Biotechnologies does this with their T-Detect test, although it does not return quantitative info. It's also proprietary as heck. But others might be able to skirt their patents, and do their own database and sequencing. BTW, Adaptive is the same company that does the clonoSEQ MRD test for blood cancers, which is becoming more common in studies of relapse.
I believe the T-Detect test was used as part of the LLS (Leukemia Lymphoma Society) COVID vaccine study. I paid for my own - $219. It was positive after my 1st dose of vaccine. But lack of quantitative info means we cannot gauge degree of protection. After 4 doses of vaccine and Evusheld. I got a BA.2 infection in May of this year.
Alas, T-detect and clonoSEQ are probably only available in the U.S. so far.
Thanks Seymour. If CXCL10 is useful only in the short term, that would certainly limit its potential. On the other hand this test can give a rapid, quantitative result from a 1 ml blood sample, and appears easily scalable, so one approach would be to run two or three tests a few weeks apart and extrapolate from there.
If my fantasies could be realized, we'd have inexpensive tests for all cytokines and hormones so we could see the variation throughout the day, week, and beyond and correlate them with diagnoses and daily health logs.
We might also like more local measurements of cytokines, since they tend to be specific for inflammation and infection.
SeymourB, the qTACT and dqTACT tests are an indirect measure of T-cells that have been primed to respond to spike protein. After a blood draw, the sample is incubated with synthetic fragments of the spike protein, which will cause primed T-cells to signal to monocytes to synthesize CXCL10 mRNA, which is then quantitated by PCR. The controls involve the cells without the spike peptides, so any background level of CXCL10 mRNA is taken into account.
I mentioned to bennevisplace and RogerPinner above that I'd gotten in contact with the senior author and ask about timeline for commercialization of qTACT and dqTACT. He got me in touch with a Hyris rep who is supposed to call me tomorrow to answer question about planned Clinical Trials. So, if any of you have questions that you'd like me to ask tomorrow, please let me know.
I just checked the Hyris website and found this news article:
Hyris' new T-cell Test is finally available to EU Countries to easily map patients' cellular immunity to SARS-CoV-2.
This is great news about commercialisation. Thanks for following up g-g.
For questions, it would be nice to know where one can look up details of the planned trials - will they register on clinicaltrials.gov ? - and when and where Hyris aims to bring the assays on stream. I hope it's not just the EU as I'm in the UK!
Thanks also for clarifying the fact that background CXCL10 is accounted for, making the test COVID-19 specific and not influenced by other CXCL10-stimulating infections or vaccinations.
bennevisplace, SeymourB and RogerPinner , sorry for my delay in posting. The Hyris rep did call as he indicated he would.
According to what I understood from my conversation with the Fergal O’Moore, the Hyris rep., Synlab in Europe has already made the dpTACT assay available to consumers. However, when I checked the Synlab website I could find no listing for the assay kit. Maybe some of our EU members can check on this in their own country and report back.
Hyris has submitted paperwork in Canada for dqTACT approval, but has not yet done so in the US. Fergal said that FDA indicated that they would likely grant EUA status to the assay if the submitting paperwork all looked good. He is in a meeting on Monday to assess the status of a pre-submission for clinical trials, and said that he’d get back in touch with me when he knows more. He said that probably at the earliest it would be 4 months before everything was wrapped up. Hyris is making the kits available to research labs at academic centers, so some of you in the US or UK might be able to get the test done at an academic center outside of an official trial.
He also said that yes indeed, Hyris is developing the dqTACT assay to measure T-cell response to other pathogens. I didn’t ask him about a test for general T-cell well-being.
Unfortunately, I forgot to ask about what's going on in the UK (really sorry guys). I did email him to ask, but haven't heard from him yet. I also sent an email to Synlab media contact, but haven't heard from them either.
Once again, thanks gardening-girl for the information you managed to get from Hyris, very relevant to all of us IMO.
I agree there's no indication on Synlab's website that they are marketing dqTACT or are preparing to.
The UK is going through another period of economic and political turmoil, so I doubt Hyris would get a commitment from within the healthcare system here, beyond an expression of interest perhaps. What concerns me is the prospect of UK researchers having to struggle for cash (along with everyone else) in tough times, without EU funding sciencebusiness.net/news/uk... and I can even imagine some important current studies being curtailed.
From the noises they have been making in their respective campaigns, neither of the two candidates for Prime Minister place much value on scientific advice, so defunding science, along with justice, makes perfect sense.
Update March 2023: Still there's no indication on synlab.com that they are marketing dqTACT or are preparing to. Disappointing, especially in light of Synlab's press release from two years ago:
Cellular immunity tests, on the other hand, isolate immune cells and stimulate them with spike proteins of the virus. This enables measurement of the amount and activity of T-Cells, which are responsible for eliminating ill or altered cells. T-Cells together with antibodies make up the human immune response. Therefore, cellular immunity tests are complementary to antibody tests.
Santiago Valor, Chief Medical Officer at SYNLAB, emphasizes the added-value of conducting quantitative IgG antibody and cellular immunity tests: “Increasing immunity is key in the fight against the pandemic, and mass vaccinations are the way forward. To examine and verify a person’s immunity status after vaccinations or an infection, however, quantitative IgG antibody and the cellular immunity tests are important complimentary measures. This holds specifically true since conducting these tests on an ongoing, large-scale basis will help us to determine how long immunity from vaccinations and infections last, and after how many months or years vaccinations must be renewed.”
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