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

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:

or below….

New paper alert! 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 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

Congratulations to Pat Schenck & Jessica Breznik on winning the Farncombe Research in Progress Awards!

Jessica Breznik (co-supervised by Dr. Deborah Sloboda) won the “Best Presentation by a PhD student” while Pat Schenck (co-supervised by Dr. Mike Surette) won runner up!  What a wonderful tribute to their skills in both research and communication – well done!

Congratulations to Sara Makaremi (PhD candidate) for winning the Gerald T Simon Award for her microscopy!

Congratulations Sara for winning the Gerald T Simons award for her presentation at the Microscopical Society of Canada and Microscopical Society of America (M&M2018) in Baltimore.

To read her award winning abstract, click here.


Congratulations to Dessi Loukov on successfully defending her PhD!

Congratulations to the newly minted Dr. Loukov on successfully defending her thesis entitled “Age-Associated Inflammation impairs Myeloid Development and Monocyte & Macrophage Function”!

The newly minted Dr. Loukov drinks from the chalice.

Dessi celebrates her thesis defence with one of her mentors Dr. Mark McDermott.

Two doctors.

Alumnus Update: Melissa Ling, Bowdish lab undergraduate, accepted to Yale University.

Congratulations to Melissa Ling, a former Bowdish lab undergraduate thesis student who was accepted to Yale University’s Masters of Medical Science in the Physician Associate Program. This prestigious program has a 3.6% acceptance rate so we are very proud of her.

Best of luck Melissa!

Pictured here in her Bowdish lab days.

Kyle Novakowski is the Bowdish lab’s newest PhD!

Kyle Novakowski successfully defended his thesis “IDENTIFICATION AND  FUNCTIONAL CHARACTERIZATION OF CONSERVED RESIDUES AND DOMAINS IN THE MACROPHAGE SCAVENGER RECEPTOR MARCO”  to become the Bowdish lab’s 4th PhD student. He’ll be joining Turnstone Biologics as a PhD scientist. We wish him very well in his future endeavours. Congratulations Dr. Novakowski!

Publication: Human-specific mutations and positively-selected sites in MARCO confer functional changes.

First author on the publication, PhD student Kyle Novakowski of Dr. Dawn Bowdish’s lab.
A common element that links ancient fish that dwell in the darkest depths of the oceans to land mammals, Neanderthals, and humans is the necessity to defend against pathogens. Hundreds of millions of years of evolution have shaped how our innate immune cells, such as macrophages, detect and destroy microorganisms.

In a new study led by Dr. Dawn Bowdish (in collaboration with Dr. Brian Golding) and her PhD student Kyle Novakowski, the team identified novel sites within a macrophage receptor, MARCO, that are under positive selection and are human-specific. The team demonstrated the importance of these sites by site-directed mutation and showed a reduction in cellular binding and uptake of pathogens. These findings demonstrate how small genetic changes in humans can influence how we defend ourselves against pathogens.

Read the full publication in Oxford University Press.

Human-specific mutations and positively-selected sites in MARCO confer functional changes. Novakowski KE, Yap NVL, Yin C, Sakamoto K, Heit B, Golding GB, Bowdish DME. Mol Biol Evol. 2017 Nov 20. doi: 10.1093/molbev/msx298.
PMID: 2916561

Bowdish lab joins the circus.

The lab that plays together stays (late nights scienc-ing) together, which is why the Bowdish lab had our annual retreat at Zacada circus school.  Here we got some very sore muscles and discussed our successes and challenges of the past year and what our goals and ambitious are for the following year. Go Team!

Our annual lab retreat for 2017 was at Zacada Circus school where we learned the trapeze, silks and ran up and down this ninja wall!
Top: Kyle, Dhanyi, Melodie, Joseph, Dessi, Grace, Pat, Mohammad
Bottom: Sara, Janine, Helen, Jessica, Dawn, Allison, Christian.