Below is an ‘explainer’ thread from Bluesky. See original here
Publication alert: “No evidence of immune exhaustion after repeated SARS-CoV-2 vaccination in vulnerable and healthy populations” @natcomms.nature.com The backstory is particularly interesting-it’s a tale of the conflicting needs of scientists & decision makers in times of disinformation ….1/n
To begin – my team was funded by the CITF to study COVID-19 infections/vaccinations in older adults & people on immunosuppressants. We had a broad mandate to look at ‘cellular & humoral immunity’ and unlike most grants there was a constant feedback to decision makers, participants & the public 2/n https://www.covid19immunitytaskforce.ca/
This meant that I got a pretty good sense of people’s worries and concerns and we could get solid data to address them. Case in point – we provided data that long-term care residents needed a 3rd dose and then a 4th – they got them and colleagues proved they prevented many infections 3/n https://www.bmj.com/content/378/bmj-2022-071502.short
In 2021 internet personalities were fretting that too many vaccines would lead to ‘immune exhaustion’. Most immunologists were not worried (explanation to follow) but I was shocked to hear in meetings that some folks on decision making tables were worried, esp, for vulnerable populations 4/n
What is this scary ‘immune exhaustion’? When you turn on an inflammatory response (e.g., by vaccination/infection) you have to have a way to turn it off. T cells that recognize an antigen multiply, make cytokines and start to express ‘off-switches’ which have names like PD-1, Tim-3 & Lag-3. 5/n
When there is a lot of antigen around (ie. during infection or vaccination) the balance between the on-switch (antigen-stimulation) and the off-switch (PD-1 & friends) favours being on – the T cells expand & differentiate & work their magic. Here PD1 is better described as an ‘activation marker’….. 6/n
…than an exhaustion marker. When the antigen decreases (ie infection or vaccine clears), the off-switches signal that it’s time to close up the inflammatory shop. It is pretty rare that antigens don’t go away but in cancer that chronic stimulation can lead to sustained expression of the PD1 off-switch. 7/n
How do you know when a T cell is truly ‘exhausted’? It expressed these markers AND it loses its function. Here’s where our study shines – we looked at the T cells’ ability to produce at least 1 cytokine (‘functionality’) or more than 1 cytokine (‘polyfunctionality’). 8/n
Repeat vaccination does not affect the T cells ability to make cytokines, even in vulnerable populations. They may express some activation markers but they are definitely not turned off. 9/n
Pity the lead author, PhD student @jennabenoit.bsky.social Her committee would grill her ‘why are you doing this- we all know vaccines don’t cause exhaustion!’ She held strong “Because policymakers & the public need us to PROVE this in THESE people”-She was strong, thorough & committed. 10/n
So why do so many people make such rash statements on whether a T cell is doing it’s thing (PD-1 = activation) vs crashing out (PD-1 =exhausted)? Above I said this disinformation began circulating in 2021 – we’ve been working on this story since then 11/n
Measuring 1 marker (eg PD1) and making wild inferences is relatively cheap & quick but measuring T cell function and analyzing these complex data is slow & expensive. Indeed we had a team of people working very hard in a clinical trials quality immune testing lab and an analysis team to generate these data. 12/n
https://healthresearch.healthsci.mcmaster.ca/single-cell-spatial-profiling-core-facility/human-immune-monitoring-services/
Learnings: Disinformation = quick to make up but hard to disprove and even immunologists and experts can have seeds of doubt sown by bad actors. Vulnerable populations deserve to be included in research. Negative data studies are impt but hard to sell (see reviews of the paper!). 13/n
Huge shout out to lead author @jennabenoit.bsky.social and the not-on-Bluesky team from our star phlebotomist/blood processor Braeden Cowbrough, flow cytometry genius Dr. Jessica Breznik, analytics guru Dr. Chris Verschoor, and HITS Team (Nichols, Hagerman, Bramson) and of course our participants. 14/14