🚨🚨New #SIRENstudy preprint 🚨🚨
Not yet peer reviewed.
papers.ssrn.com/sol3/papers.cf…
A 🧵 1/n
@victoria_jhall @bealelab @SMHopkins

First up thank you to the amazing participants in #SIRENstudy 🙏 Without you, no study. NHS staff continuing to go above and beyond in really challenging times 🤩 #notAllHeroesWearCapes

And, of course, our thanks to the NHS sites across all 4 countries!

2/n

We wanted to find the correlate of protection (CoP) against Delta infection.
No study so far has managed this.
Aficionados might want to skip ahead: papers.ssrn.com/sol3/papers.cf…
3/n

4/n
Jargon busting: What is a CoP?
A: something you can measure in the lab that predicts immunity from the disease.
In principle, you could measure anything … in blood, serum, saliva wherever works best!
Existing CoPs in clinic (eg Hep B, Rubella) are blood tests for antibodies.

If you have a numerical CoP, you could use it to:
👉 plan booster doses 💉
👉 identify vulnerable groups
👉 triage prophylactic measures 💊
… and you can take these steps ahead of time. 5/n

Why has it been difficult to find a numerical CoP so far?
Study needs:
👉regular PCR screening & sequencing 🧬 +ve specimens
👉regular serum samples 🩸
👉the real kicker: you don’t know who is going to turn out to be a case when you’re collecting. So: your study must be vast. 6/n

Your labs need:
👉massive capacity. @asherichia @EPS_Porton has tested over 1 million sera.
👉best-in-class assays: @MaryYiWeiWu ‘s live 🦠 microneutralisation assay.
👉statisticians 🪄 @FerdinandoInsa1
👉funding 💰 @UKRI_News 7/n

As a partnership - with UKRI funding 💰 gov.uk/government/new… - #SIRENstudy and @TheCrick teamed up.
Our Q: does a numerical CoP exist for vaccine-induced immunity?

3 methods tweets next 8/n

Methods 1
👉Participants after 💉💉, and before 💉💉💉
👉AZ / BNT for doses 1 & 2
👉All anti-N IgG negative at start
👉Cases = Delta infections & sequenced 🧬
👉Controls = Age/sex/region matched, PCR + N neg thru Delta wave. 9/n

Methods 2
In the labs we measured:
👉Anti-nucleocapsid IgG
👉Anti-S IgG
👉Live virus 🦠 microneutralisation; Delta, Ancestral, Omicron BA.1

[Nucleocapsid IgG lets us check no prior infections in cases/controls.]
10/n

Method 3
👉Model waning 📉 … about 8% per week
👉Infer Ab levels to 7d before PCR+ in cases
👉Infer Ab levels to matched calendar time after dose 2 in controls
i.e. give cases + controls same number of days to wane since dose 2.
👉cond logistical regression to find CoP. 11/n

Results: Delta neutralising Ab titres > 40 at 7 days before infection are CoP

A live virus neutralising titre >40:
🛑 89% reduction in odds of infection [95% CIs 69-96%; p<0.0001]
🛑 extra benefits at higher titres
And, much more in the preprint 12/n

There are some limitations to our study:

- HCW study. Not the oldest, or immunosuppressed members of population.
- You need several sera pre-infection to calculate trajectories 📉
- Our assays use live 🦠, so hard to do in clinical labs
- Again: not yet peer reviewed.

13/n

To summarise, we report the numerical CoP for Delta infection after two doses of vaccination.
This is an ongoing collab between UKHSA’s #SIRENstudy and @TheCrick.

14/n

At #ECCMID2023, speak to co-first Ana Atti today:

23 - New and Emergent Pathogens
LB076 - Antibody correlates of protection against Delta infection after vaccination: a nested case-control within the UK SIREN Study
18/04 - 12h - 13:30

Ana twitterless; try @asherichia

15/n

With thanks to coauthors:
Ana Atti, Sarah Foukles, Michelle Cole, Tim Brooks, Amanda Semper, Andre Charlett (not on Twitter), @FerdinandoInsa1 @asherichia @EzraLinley @SMHopkins @bealelab @victoria_jhall
papers.ssrn.com/sol3/papers.cf…

/ fin