Category Archives: Publications

Publication: “Rationalizing recommendations for influenza and COVID-19 vaccines”

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Rationalizing recommendations for influenza and COVID-19 vaccines
Jessica A. Breznik, Matthew S. Miller, Dawn M.E. Bowdish
Article 127775

Supplementary Tables and references

Bluesky Explainer here.

I’m excited to share our review “Rationalizing recommendations for influenza and COVID-19 vaccines”, which we feel makes a strong case for universal influenza and COVID-19 vaccination policies. With almost 500 references & 8 supplementary tables it’s a beast so let me break it down for you….1/n

https://www.sciencedirect.com/science/article/pii/S0264410X25010722#ec0005

We started this >a year ago after conversations with immunologists, policy-makers, and the general public. We felt there were misunderstandings about how well COVID-19 vaccines work. We argue that they work as well or better than influenza vaccines so vaccination policies should be similar. 2/n

Like influenza, everyone but newborns has been exposed to COVID-19 through either vaccination or infection so we only reviewed studies in the post-Omicron/post-vaccine era. There is no doubt that the burden of disease has changed in the Omicron/vaccine era, but does that mean COVID is over? 3/n

Comparable data is hard to find, but when we looked at 2022/23 & 2023/24 data we see that deaths are still higher for COVID than influenza BUT looking at % hides the fact that COVID-19 is more contagious and in 23/24 there were almost 3x as many COVID hospitalizations than influenza. 4/n

There’s a common belief that COVID-19 vaccines don’t provide very good protection against symptomatic infection -is this true? These data are very, very hard to compile because the pace of variant replacement and vaccine changes has been dizzying 5/n

Before we get to the data – I just want to give a huge shoutout to @belongia.bsky.social for leading so many high quality studies on influenza effectiveness – look how easy to compare year-to-year. 6/n

Now look at how complicated it is to compare COVID-19 vaccine effectiveness. In influenza studies it is often possible to assess which strain a person was infected with so you can assess vaccine effectiveness by strain. COVID-19 vaccines are almost never matched with the circulating variants.. 7/n

…but despite that disadvantage, levels of protection from symptomatic infection and severe disease are similar between COVID & influenza vaccines. Note that protection against symptomatic infection is VERY hard to estimate because people who don’t get sick don’t get tested. 8/n

There has been some frustration that COVID-19 vaccines don’t last longer but neither does protection from either infection or vaccination for other viruses. When we compare protection < 3 months and > 3 months, COVID-19 vaccines look pretty good, esp considering rapid variant change 9/n

We also make a case to increase to increase the range of vulnerable populations. Canada has been a leader in including congregate living and equity-deserving groups in priority populations (#elbowsup !) but people living with lung and heart issues should be included 10/n.

Vaccine programs are decided by more than efficacy and efficacy – here’s a summary of what the National Advisory Council on Immunization (Canada) includes. Our review doesn’t address the programmatic, cost, and social considerations, which are also important. 11/n

There are still a lot of unknowns, but we feel strongly that universal & free COVID-19 and influenza vaccines would be a good investment in health, health systems, and attendance at work and school. Thank you to the brilliantly detail oriented Dr.@jabreznik.bsky.social and infl Dr Matt Miller Fin!

Publication: “Mapping the intersection of demographics, behavior, and government response to the COVID-19 pandemic: an observational cohort study”

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Kennedy, K.M., DeJong, E.N., Chan, A.W. et al. Mapping the intersection of demographics, behavior, and government response to the COVID-19 pandemic: an observational cohort study. BMC Glob. Public Health3, 52 (2025). https://doi.org/10.1186/s44263-025-00162-w

Bluesky Explainer thread by Dr. Kate Kennedy here:

Publication: “No evidence of immune exhaustion after repeated SARS-CoV-2 vaccination in vulnerable and healthy populations”

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Benoit, J.M., Breznik, J.A., Wu, Y. et al. No evidence of immune exhaustion after repeated SARS-CoV-2 vaccination in vulnerable and healthy populations. Nat Commun16, 5219 (2025). https://doi.org/10.1038/s41467-025-60216-3

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

Publication: Minimal Impact of Prior Common Cold Coronavirus Exposure on Immune Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination or Infection Risk in Older Adults in Congregate Care

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Link to publication here.

Link to Bluesky “Skeetorial” here and reproduced below without images:

New paper! “Minimal Impact of Prior Common Cold Coronavirus Exposure on Immune Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination or Infection Risk in Older Adults in Congregate Care”. For those of you who follow our #COVID work, read on for the story behind the story. 1/n

Remember reports like this one from the beginning of the pandemic? How could some older adults show such resilience to COVID compared to their peers? Some thought that they might have cross reactive immunity due to exposure to the related ‘seasonal’ or ‘common cold’ coronaviruses. 2/n
https://www.cbc.ca/news/canada/ottawa/102-year-old-woman-recovers-from-covid-19-1.5567189

After all, our @mcmasteru.bsky.social colleagues, Dr. Mark Loeb & team had shown years earlier that seasonal/common cold coronaviruses caused a lots of infections in long-term care and others had investigated whether these might protect kids from COVID…. 3/n
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0108481

….while others have shown that can be very deadly in residents of long-term care (reminding us that words matter and calling them ‘common colds’ minimizes risk – common viruses can still make people very sick, but that is rant for another day). So could pre-existing immunity be protective? 4/n
https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00018-1/fulltext

Alternatively, maybe older adults got so sick because a life of exposure to these viruses ‘used up’ all the immune cells that could be used to respond to SARS-CoV-2 or COVID vaccines(i.e. ‘immune imprinting’, a phrase I came to hate along with ‘original antigenic sin’ as it was so misused) 5/n

To find out we tested whether antibody levels for the coronaviruses OC43, HL63, and 229E were higher/lower in people whose first COVID infection was an early Omicron variant and found they were not. Therefore it is unlikely these are either protective or problematic 6/n

What about pre-existing anti-coronavirus T cells? We looked at memory CD4+ and CD8+ T cells against the M & N proteins (indicates prev infections) and Spike (vaccine and infections). No evidence that these differed between those who did/did not get an infection (7/n)

What was a correlate of protection? Anti-RBD-IgG & neutralizing antibodies to the ancestral virus (which is all the residents would have been vaccinated to at that point). Unlike others we didn’t find that (serum) IgA was a correlate of protection. 8/n

Pre-existing immunity to common cold coronaviruses didn’t protect against SARS-CoV-2/COVID but might our vaccines and immunity alter immune responses to seasonal coronaviruses? Antibodies to other coronaviruses increased a bit (‘back-boosting’) after COVID infection or vaccination…. 9/n

But I doubt this will have much effect on the prevalence of other coronaviruses who follow a pretty consistent yearly/biennial or big wave/small wave pattern in the Northern hemisphere. We don’t know why but we do know that immunity doesn’t last long so a small boost from COVID infection/vaccination is not likely to make a difference 10/n
https://www.nature.com/articles/s41591-020-1083-1

Caveats: Only measured peoples first infections in the early Omicron era, only older adults living in LTC and retirement homes, vaccines would have been against the ancestral virus – things might be different in other populations/variants/vaccines. 11/n

Huge shout out to Braeden Cowborough for doing all those titres – that’s a lot of plates – and to Dr Jessica Breznik (former @miramcmaster.bsky.social currently @mcmasternexus.bsky.social PDF) for analytic skills. Thanks to the rest of the COVID-in-LTC team @mcmasteriidr.bsky.social

Publication: Canadian Immunity Task Force (CITF) Hema-Net Serosurveillance Meeting

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Serosurveillance describes using blood samples to determine what percentage of the population has been exposed to a pathogen or has been vaccinated by measuring the presence or absence of antibodies to the pathogen or vaccination. During the COVID-19 pandemic Dr. Bowdish and team built a network of long-term care homes to measure vaccine responses and infection rates, but this infrastructure could have been used to measure virtually any infection or any antibody response. The Hema-Net community came together February 14-16 to present data and share experiences using serosurveillance and published this report. Unfortunately, no funds were made available to continue Dr. Bowdish’s or others serosurveillance networks.

See the CITF website here.

See the English report here.

See the French Report here.

Publication: Reassuring humoral and cellular immune responses to SARS-CoV-2 vaccination in participants with systemic sclerosis

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Benoit JM, Breznik JA, Huynh A, Cowbrough B, Baker B, Heessels L, Lodhi S, Yan E, Bhakta H, Clare R, Nazy I, Bramson JL, Larché MJ, Bowdish DM. Reassuring humoral and cellular immune responses to SARS-CoV-2 vaccination in participants with systemic sclerosis. Immunol Lett. 2024 Sep 19;270:106929. doi: 10.1016/j.imlet.2024.106929. 

Below is a Bluesky thread that summarizes and explains our manuscript. Click here to read it on Bluesky.

New publication alert! “Reassuring humoral and cellular immune responses to SARS-CoV-2 vaccination in participants with systemic sclerosis” Read on to learn why we did this study and why it is important. 1/n https://www.sciencedirect.com/science/article/pii/S0165247824001032?via%3Dihub

https://bsky.app/profile/msmacrophage.bsky.social/post/3l5zdipjxwe2o

Systemic Sclerosis(SSc) is a rare autoimmune disorder that causes fibrosis of the organs. Because it is caused an immune system gone awry, patients and their doctors were concerned that their immune systems might not respond to the vaccine and leave them less protected 2/n

Because SSC is an autoimmune condition, people generally take immunosuppressive drugs, which can also lead to lower vaccine responses and higher risk of infection. We investigated whether antibody or T cell responses to vaccination were affected in SSC. 3/n

Good news! People with SSC made the same amount of antibodies to the receptor binding domain of the Spike protein (i.e, the bit of the virus that the virus uses to get into us) after their second, third, and fourth SARS-CoV-2 vaccinations. 4/n

More good news! T cell responses to vaccines are thought to help with severe disease and may offer some cross-variant protection. Following the second, third, and fourth SARS-CoV-2 vaccinations, participants with SSc had T cell responses = those without SSC. 5/n

For the immunology geeks: People living with SSc have elevated levels of serum cytokines associated with T cell differentiation. Could this change Th1/2/17/reg mix posts vaccination? Nope. 6/n

Caveat#1: This is a small study (because a rare disease) and we couldn’t investigate all the different drugs that people are on. For more info on how drugs affect vaccination responses see our other studies 7/n https://acrjournals.onlinelibrary.wiley.com/doi/full/10.1002/acr2.11697

Caveat #2: This is very much a comparison of the quantity of immune responses, not the quality. There could still be qualitative differences in immune responses that we didn’t catch but… 8/n

…even though there is very little data on whether SSC is associated with higher infection risk or poorer outcomes what little exists doesn’t find a massive difference compared to the general population 9/n https://acrjournals.onlinelibrary.wiley.com/doi/full/10.1002/acr.25226

Take home message #1: Participants with SSc mount similar responses to SARS-CoV-2 vaccination as controls who do not have autoimmune conditions. 10/n

Take home message #2: Many ppl with autoimmune conditions are afraid that vaccination is unsafe for them because they know their immune system is a bit wonky. It is not the disease that affects immune responses, rather it’s some, not all, drugs at some, not all, doses. 11/n

Thanks to emerging leader & 1st author Jenna Benoit (graduating & looking for a job next year – hint), rheumatologist extraordinaire, Dr. Maggie Larche, cellular immunologist Dr. J. Breznik & J Bramson, team Antibody (Nazy, Huynh) & with special thanks to…..12/n

….our participants. People with SSC often have skin changes which makes blood draws especially hard. Thank you for your commitment to our study and huge props to our exceptional phlebotomist/RC Braeden Cowbrough – our unsung hero. 13/n Fin.

Publication: “Monocyte-driven inflamm-aging reduces intestinal barrier function in females”

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Click here to access: Monocyte-driven inflamm-aging reduces intestinal barrier function in females published in Immunity and Ageing, September 2024.

This publication by former PDF, Dr Candice Quin and team, discovers that inflammatory markers and gut permeability increase with age, but the leaky gut seems to be a female specific phenomena in both mice and humans.

Bluesky explainer thread below and here https://bsky.app/profile/msmacrophage.bsky.social/post/3l5ethyexgp2u

New publication alert! “Monocyte-driven inflamm-aging reduces
intestinal barrier function in females” by lead author Dr Candice Quin @uniofaberdeen.bsky.social. Read on for some surprising insights into sex differences in aging, the microbiome, inflammation, and the ‘leaky gut’ hypothesis….1/n

With age levels of inflammatory mediators (cytokines, CRP, & others) increase in the blood and tissues. This is often called ‘inflamm-aging’, and higher than age-average levels of these mediators are associated with chronic disease, frailty, and other age-associated ills. 2/n

Men & women age differently (‘men die quicker, women live sicker’)so it stands to reason they might ‘inflam-age’ differently, but very few studies on aging investigate sex differences in the aging trajectory. We looked at cellular & soluble inflammatory markers and saw sex differences! 3/n

We were surprised by the magnitude of sex differences but immunology is literally one of the worst disciplines when it comes to reporting by sex https://elifesciences.org/articles/70817
By why do we ‘inflamm-age’ in the first place? Might the mechanisms of inflamm-aging differ by sex 4/n

One of the major theories is that with age a dysbiotic microbiota causes the gut to become leaky (alternatively, the gut gets leaky with age and this alters the microbiota). Bacterial products leak out and cause inflammation. We’ve published in mice, others in other model organisms 5/n https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30112-9?elsca1=etoc&elsca2=email&elsca3=1931-3128_20170412_21_4_&elsca4=Cell%20Press

Evidence for the ‘leaky gut’ hypothesis is weak in healthy humans (despite what the probiotic industry might say). Leakiness is generally found in people who have comorbidities, or are frail so we looked at healthy/non-frail male (41) females (54) btw 20-102 yrs and were surprised to find…6/n

…that women appeared to have leakier guts over the life course (as measured by the serum marker zonulin- imperfect), and only women had evidence of an age-associated increase in the bacterial product LPS in their serum. Could the leaky gut hypothesis be female specific? 7/n

Human studies are observational so we turned to mice to understand the chain of causality. Old female, but not male, mice did indeed have leakier guts and this seemed to be caused by TNF produced by the elevated number of circulating inflammatory monocytes. 8/n

Tl;dr The age-related leaky gut -> increased circulating bacterial products -> systemic inflammation hypothesis may only be true in females! (also – always investigate sex in your research) 9/n

Why? Well the female gut changes dramatically during pregnancy to increase nutrient absorption – perhaps that is why women seem to have more permeability over the life-course. We are doing some cool ongoing studies in vitro looking at male vs female monocytes ability to break the gut barrier. 10/n

Caveats: This was a non-frail, mostly white population – aging & immunology studies show tremendous differences by location so needs to be reproduced. Gut permeability measures were done by looking at serum markers – easy on the participant but indirect at best. 11/n

Thanks to the whole (unfortunately not on Bluesky team)! This was an incredibly fun and challenging project to work on but has cemented my commitment to considering sex in all the research we do. 👩‍🔬🧪🦠🚨 12/12

Publication: Chronic TNF in the aging microenvironment exacerbates Tet2 lost-of-function myeloid expansion

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Download PDF here.

Link to journal here.

Abstract: Somatic mutations in the TET2 gene occur more frequently with age, imparting an intrinsic hematopoietic stem cells (HSCs) advantage and contributing to a phenomenon termed clonal hematopoiesis of indeterminate potential (CHIP). Individuals with TET2-mutant CHIP have a higher risk of developing myeloid neoplasms and other aging-related conditions. Despite its role in unhealthy aging, the extrinsic mechanisms driving TET2-mutant CHIP clonal expansion remain unclear. We previously showed an environment containing tumor necrosis factor (TNF) favors TET2-mutant HSC expansion in vitro. We therefore postulated that age-related increases in TNF also provide an advantage to HSCs with TET2 mutations in vivo. To test this hypothesis, we generated mixed bone marrow chimeric mice of old wild-type (WT) and TNF–/– genotypes reconstituted with WT CD45.1+ and Tet2–/– CD45.2+ HSCs. We show that age-associated increases in TNF dramatically increased the expansion
of Tet2–/– cells in old WT recipient mice, with strong skewing toward the myeloid lineage. This aberrant myelomonocytic advantage was mitigated in old TNF–/– recipient mice, suggesting that TNF signaling is essential for the expansion Tet2-mutant myeloid clones. Examination of human patients with rheumatoid arthritis with clonal hematopoiesis revealed that hematopoietic cells carrying certain mutations, including in TET2, may be sensitive to reduced TNF bioactivity following blockade with adalimumab. This suggests that targeting TNF may reduce the burden of some forms of CHIP. To our knowledge, this is the first evidence to demonstrate that TNF has a causal role in driving TET2-mutant CHIP in vivo. These findings highlight TNF as a candidate therapeutic target to control TET2-mutant CHIP.

Bluesky explainer thread here:
New Paper Alert: “Chronic TNF in the aging microenvironment exacerbates Tet2 lost-of-function myeloid expansion” published in Blood Advances #ImmunoSky #CHIP https://authors.elsevier.com/sd/article/S2473952924003860 (1/n)

Over time the progenitor cells (#stemcells) in our bone marrow acquire random mutations, with some genes being more likely to acquire these mutations than other. The Tet2 gene is one that acquires mutations. This is a problem because it regulates other genes through methylation (2/n)

Hematopoetic #stemcells with Tet2 mutations favour production of myeloid cells (#neutrophils #monocytes) over lymphoid cells (#Tcells #Bcells) and can outcompete stem cells that don’t have Tet2 mutations.(3/n)

If too many white blood cells originate from these mutants it is called Clonal Hematopoesis of Indeterminate Potential or #CHIP. CHIP is associated with an increase in mortality, and pneumonia (see prev paper), because immune cells with these mutations don’t work as well (4/n) https://shorturl.at/JNk6d

With age the proportion of Tet2 mutant cells increases and it is thought that the increased #inflammation that occurs with age contributes. Darwinian evolution happens in the bone marrow and stem cells with Tet2 mutations can outcompete (i.e. replicate more, make more white blood cells) than those without (5/n)

We investigated whether Tet2 mutant stem cells could outcompete others in the presence of the inflammatory cytokine TNF, which increases with age. We put a mix of normal and Tet2-/- stem cells into old mice that had lots of TNF and those with none (TNF KO). 6/n

Stem cells with Tet2 mutations could outcompete normal cells in old mice that had lots of TNF but not in TNF knockout mice. The aging inflammatory microenvironment contributes to CHIP! (7/n)

Cool finding- People with newly diagnosed #rheumatoidarthritis have lots of TNF and had low level of Tet2 and other CHIP mutants that went down as they started anti-TNF or anti-inflammatory therapy! Proof this happens in humans too (8/n)

Huge thank you to not on Bluesky Drs Michael Rauh (Queens), Candice Quin ( @uniofaberdeen.bsky.social ), Maggie Larche (UCalgary), Salman Basrai&Sagi Abelson @oicr.bsky.social and team. (9/9)

Publication: Neutrophil-mediated innate immune resistance to bacterial pneumonia is dependent on Tet2 function

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https://bsky.app/profile/msmacrophage.bsky.social/post/3kubwknbcts2e
Click here for the full thread from Bluesky highlighting the major findings of the paper.
To see the full paper click here:
To see the commentary click here:



Bluesky thread:

Let me tell you about the #BowdishLab & friend’s most recent paper “Neutrophil-mediated innate immune resistance to bacterial pneumonia is dependent on Tet2 function”, led by Dr. C. Quin (now at @uniofaberdeen.bsky.social) @jclinical-invest.bsky.social https://www.jci.org/articles/view/171002
Tet2 is gene that is involved with methylating genes and therefore changing gene expression. Sometimes spontaneous mutations of Tet2 in hematopoetic stem cells (HSC) occur. These mutants tend to produce more myeloid cells (monocytes/neutrophils).
These myeloid producing HSCs tend to be more fit in the aging bone marrow (Darwinian survival of the fittest) and overtime, more and more of your myeloid cells are made from these Tet2 mutant clones.
In extreme cases this can lead to myelodysplastic disorders or cancer, but sub-clinical CHIP or clonal hematopoeisis of indeterminant potential occurs in many older adults.
People with CHIP (i.e., too many of their myeloid cells are made from Tet2 mutant progenitors) are prone to all sorts of conditions (e.g., heart disease) and pneumonia. We hypothesized that pneumonia risk might be due to changes in innate immune/myeloid cell function.
Mice defective in Tet2 did very poorly during Streptococcus pneumoniae infection (the most common cause of community acquired pneumonia in older adults), because their neutrophils were less able to kill bacteria.
We are excited about this @jclinical-invest.bsky.social publication because it is the first mechanistic explanation for the increased risk of pneumonia in CHIP. Generally CHIP is thought to affect macrophage function, but it clearly affects neutrophil gene expression & function as well.
Many thanks to Dr. Elsa Bou Ghahem for her most excellent Commentary https://www.jci.org/articles/view/181064 and for the great editorial & reviewer experience @jclinical-invest.bsky.social
Research Team:Candice Quin, Erica N. DeJong, Elina K. Cook, Yi Zhen Luo, Caitlyn Vlasschaert, Sanathan Sadh, Amy J.M. McNaughton, Marco M. Buttigieg, Jessica A. Breznik, Allison E. Kennedy, Kevin Zhao, Jeffrey Mewburn, Kimberly J. Dunham-Snary, Charles C.T. Hindmarch, Alexander G. Bick, Stephen L. Archer, Michael J. Rauh, Dawn M.E. Bowdish

Publication: “Immunomodulatory drugs have divergent effects on humoral and cellular immune responses to SARS-CoV-2 vaccination in people living with rheumatoid arthritis”

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Jenna Benoit (PhD candidate) has published her first, first author paper characterizing how immune responses to vaccination differ in people living with rheumatoid arthritis. We found some interesting new drug-immune interactions.

See the full paper here.

See thread here: https://bsky.app/profile/msmacrophage.bsky.social/post/3kh2uswvqtm2u

or below….

New paper alert! @jennabenoit.bsky.social and team studied COVID-19 vaccinations in people living with rheumatoid arthritis who are on immunosuppressive drugs and found some interesting, and to our knowledge, unknown effects of specific drugs 1/n

Almost all studies of vaccine immunogenicity (i.e., how strong an immune response is to a vaccine) focus on antibody responses. Measuring the amount of antibodies produced is cheap and (relatively) easy; however, in the Omicron-era these are less predictive of protection than you might think 2/n

When investigating anti-receptor binding domain (RBD) antibodies @jennabenoit.bsky.social and team found that -unsurprisingly- people living with RA and men had lower antibody responses (men have lower antibody responses to vaccination in general), and people with COVID had higher responses (i.e., that hybrid immunity you’ve heard so much about) 3/n

What caused these lower antibody responses? DMARDs (disease modifying anti-rheumatic drugs),and anti-TNF were not associated with lower antibody levels, the effect of steroids was not significant, but costimulation inhibitors reduced antibody levels 4/n

Important caveat: The effect of co-stimulation inhibitors was about the same as being a biologic male, so whether this reduction is associated with increased risk of infection or not is not something we can comment on 5/n.

We didn’t see an effect of drugs on neutralizing antibodies (i.e., antibodies that bind the virus really well and prevent it from entering us), but we did not have enough people on some of the drugs to really investigate this 6/n.

My favourite part: CD4+ and CD8+ T cell responses to vaccination are much, much harder to measure (each dot on the graph costs about $350 and 3+ hrs of time – hence the ‘team’ I keep mentioning) but we know that they are important for preventing infection.7/n

We found that people living with RA had lower CD4+ T cell responses (= ‘helper’ cells that support many aspects of the immune response to infection & vaccination), those who had had COVID were higher – more of that hybrid immunity you’ve heard about. 8/n

BUT even though we had a small number of people on JAK inhibitors, those who were on them had markedly lower CD4+ responses. The effect of co-stimulation inhibitors was not as apparent – but again low numbers of participants so hard to say. 9/n

Speculative side note: We use influenza vaccine as a control. Everyone has had exposure as kids so this measures a memory response made prior to having been vaccinated. Co-stim inhibitors don’t affect influenza but JAK inhibitors do – therefore no defect in pre-drug immune responses? 10/n

CD8+ T cell responses (‘killers’ of virus infected cells), were higher in men (previously known), and didn’t seem to be lower in most drugs, except maybe steroids. 11/n

Caveats: Our study was small and due to the fact we were measuring 1,2,3 doses, we were recruiting fast and furious and didn’t capture as many people on some of the drugs as we would have liked,so all results need to be replicated. 12/n

Clinical relevance: Some of these drugs are associated with increased risk of severe disease (see text for references) and by learning which aspects of the immune response they affect, we learn which aspects of the immune response are required for a successful vaccine. 13/n

Deepest appreciation for our research participants, the Canadian Arthritis Patient Alliance (see website for talks on this topic), the SUCCEED investigator team, our technical staff, fundign from the Public Health Agency of Canada, and you for reading to 14/n