We have new results on T cell responses to #Omicron, and its good news!
Paper submitted for peer review & preprint:

📢TL;DR: Most of your T cell responses from vaccination or previous infection still recognise Omicron.
#Getvaccinated #GetthoseTcellsnow
We describe T cell responses to #Omicron compared to original SARS-CoV-2 in ppl vaxxed with JnJ (1x and 2x) and Pfizer (2x). We also studied Omicron-infected patients and compared their T cells to patients hospitalised in previous waves (n=138 participants in total).
Why did we do this study?
Omicron has >30 mutations in its Spike protein, and many studies now show that this knocks out a lot of the neutralising antibody binding sites. 💩
We wanted to check if other parts of the immune system - T cells - still recognise Omicron Spike. 🎯
Unlike antibodies, which bind in hotspots, T cells can target the whole of Spike - shown as a mountain range, with Omicron mutations in red.
So we expect that T cells would still be able to target Omicron- even though it has lots of changes, there is lots of Spike NOT mutated.
Why is this important?‼️👇🏾
While antibodies block infection, T cells come in and kill infected cells, preventing the virus from growing & spreading more & causing worse disease
They can't prevent you from getting infected, but they can minimise the damage that comes afterwards..
How did we do this study?
We measured T cell responses using peptides -small chopped up bits of proteins that T cell recognise.
We compared a pool of peptides based on the original (“Ancestral”) SARS-CoV-2 and Omicron spike protein.

🙏🏾🙏🏾 @SetteLab for sending us the peptides
We isolate white blood cells from patient samples,
mix the cells with the peptides, and then use a technique called intracellular cytokine staining and flow cytometry, to check for a T cell response.
We measured both CD4 ‘helper’ cells and CD8 ‘killer’ cells.
Results - First CD4 T cells:
Compared to ancestral virus, there was a small decrease when tested against Omicron spike.
This was a consistent decrease across all study groups.
However, most of the CD4 T cell response was still there and cross-recognised Omicron.
Next, CD8 T cells:
Here too, compared to ancestral virus, there was a small decrease when tested against Omicron spike for some of the groups, no major change for most people.
If we plot fold-change of Omicron responses compared to ancestral, we see that 70-80% of T cell responses are preserved.
This means that most people who were vaccinated with 1x / 2xJnJ, 2xPfizer & those who had COVID 1-6 mo ago, still have T cells that can recognise Omicron.
Important to point out - there were a minority of CD8 T cell “knockouts”.
These represent people who may have had a narrower response targeting only a few regions in Spike, that happened to coincide with mutations in Omicron and a specific HLA bkg – we’ll be following up on these
When we compared the cross-reactivity of T cells to Omicron with Beta and Delta variants, we found that they were very similar, even though Omicron has 3-4x more spike mutations than Beta and Delta.
This emphasises just how robust the T cell response is.
This is consistent with what we recently published on cross-reactivity of the T cell response to the Beta variant:
To get a full picture of immunity, @sigallab and @PennyMo70026063 measured neutralising antibody responses in the same participants.
You can see that while neutralisation is substantially decreased in most people, overall their T cell responses are only impacted in a small way.
South Africa’s COVID epidemic is characterised by virologically distinct waves, each dominated by a different form of the virus – first original, then Beta, Delta and now Omicron.
Next we tested blood samples from each wave & compared them to patients from the 4th wave (Omicron)
We measured T cell responses to Spike, Nucleocapsid and Membrane proteins (viral proteins most targeted by T cells when you become infected).
Omicron-infected patients had T cell responses in the same range as patients hospitalised with ancestral, Beta or Delta virus infection.
Finally, we also tested some Omicron-infected patients with ancestral and Omicron Spike, and there was hardly any difference between them, showing that most of the parts of Spike that people make T cell responses to are conserved - parts that are not affected by the mutations.
Despite Omicron having so many mutations, and lower antibody activity, the majority of T cell responses, from vaccination or infection, cross-recognise the new variant.
The limited effect of Omicron’s mutations on the T cell response suggests that vaccination or prior infection may still provide protection from severe disease
Well-preserved T cell immunity to Omicron is consistent with early clinical observations from South Africa, UK and Scotland of lower severity - a decoupling of case loads from hospitalisations, and shorter hospital stays, which may be due to this remaining T cell immunity
Finally: The resilience of the T cell response demonstrated here also bodes well in the event that more highly mutated variants emerge in the future.
We still need to see how long T cell immunity lasts, but after SARS1 it was still detectable after 17yrs..
Who did the work? 🔬🧪🩸😓
Dr Roanne Keeton is the amazing researcher who generated much of the T cell data, along with my lab team, and I co-led this work with the brilliant Dr Catherine Riou.
This work was also made possible by wonderful collaborators, esp. @Ntobekon and @SetteLab, @VreemdeSiekteDr, @sigallab, @PennyMo70026063, @tuliodna, @Alba_Grifoni, @BhimanJinal, @LindaGailBekker, @houzhou, @just_Thande, @KhadijaKhan24 and many others who contributed to this work
Thank you to all the volunteers and patients who made this work possible, and our funders @MRCza @EDCTP @CIDRI_Africa @UCTIDM @UCT_news @wellcometrust
Shout out to @Biocair for all their efforts in getting critical reagents to us when they were stuck in Dubai because of NONSENSICAL TRAVEL BANS

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