Ash Otter Profile picture
Apr 22 22 tweets 7 min read
New #SIREN🚨 preprint out (and also being presented at #ECCMID2022 this week)...we did a cross-sectional analysis of ~6,000 SIREN participants after their vaccinations

Thread on our results and few interesting ones...🧵… @UKHSA @SMHopkins
First up, SIREN is an incredibly big research we were able to select samples from participants that provided a baseline sample (done when enrolled into SIREN) but after they were vaccinated, giving us an initial pool of ~6,000 participants...
All samples were then tested for anti-spike and anti-nucleocapsid antibodies

We then split these participants into 3 groups: naive (no PCR+), those with history of a PCR+, and then those with no PCR+ history but anti-N positive

(but more on why this is important later)
Similar to what we've/many others have shown, those with previous infection have a much higher antibody response post dose 1 compared to naive individuals, just over 10x higher
But post dose 2 we also see that those with prior infection have have a slightly higher antibody response compared to two dose vaccinated naive individuals (2x higher)
We see a clear age difference in vaccine responses (dose 1 and 2)...younger participants (red <25, blue 25-34 etc) have higher antibody responses than older individuals (orange >54)
Then comparing antibody titres following vaccination vs infection alone: having 2 doses gives a far higher antibody responses than infection...And those with prior infection and 2 doses have an even higher response!
Then we looked at dosing intervals (timing between dose 1 and 2)...because of the change by JCVI in Jan 21 from 3 weeks to up to 12, we have a nice mixture within SIREN of people at a different number of weeks (from 3 to 12) between doses
As many others have shown (including @PITCHstudy ), the longer time between dose 1 and 2, the higher the antibody response. When splitting this further, we see this is true independent of age
Generally, there's a 9x difference in antibody titres between 2-4 week and >10 week dosing interval across all ages

But we also see differences across ages with same interval, up to 3x difference...e.g. at 4-7 week interval, those aged <25 = 7,320, whereas those aged >54 = 2,368
So this data supports the dosing interval being 10-12 weeks, something the CDC also just recommended similar to JCVI:…
Then onto prior infection...we were really stumped for a bit why some of those with previous infection (with PCR+) had a far lower antibody response after dose 1 than those with no PCR+ but anti-nucleocapsid positive...
Then we thought whether our good old friend timing has anything to do with this (like dosing interval)...
And was! Timing between a participants infection and their first dose (x axis, in months) had a rather big factor in their post dose 1 antibody response
Antibody titres increased up until a plateau at about 8 months between infection + dose 1, which gives a very similar antibody response to those with previous infection but no history of PCR+
But why would those with no PCR+ history but evidence of infection have similar antibody response to those 8-12 months between infection & dose 1?
Timing again...~8 months prior to HCWs being vaccinated was the roughly the time of the first infection wave, when our PCR testing capacity was low = less people having history of PCR+, but serological evidence of infection
Whilst this data may look like people should wait 8 months between infection and first dose, this is only for the first dose...

Regardless of how many months between infection + vaccination, post vaccination titres are all very similar after dose 2
I'll stop there...but the takeaway messages are that ⬆️ dosing interval is good, and if you've been previously infected, vaccinations are a huge boost to your immune system. Work is now well underway in SIREN looking at the impact of timing, boosters and prior infection
Huge thanks to all the SIREN participants that have volunteered, lab staff (this work involved testing ~30,000 baseline samples on two different assays!) and all the help from everyone from data exports, redrafts, reanalysis, stats help etc etc 😄
Didn't think my graph would ever make it to the DailyMail 😂…

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