Thread by @bealelab

Three doses of vaccine protects healthy people reasonably well against Omicron. The critical question is: how well will vaccines protect the most vulnerable? Here we look at a correlate of vaccine efficacy in a vulnerable group. @TheLancet with @EdjCarr. thelancet.com/journals/lance…

2/n We report authentic live virus neutralisation (best correlate of vaccine efficacy) of Omicron & Delta by haemodialysis (HD) patients after 3rd doses of BNT162b2.
Funding @Kidney_Research @NKF_UK @PKDCharity @KidneyWales
Thanks to patients taking part & @ukkidney colleagues.

3/n HD patients had partial protection during Delta wave
VE estimates against hospitalisation of 38% (95% CI 0-57)
medrxiv.org/content/10.110…
@SamiraBell76 @drpaddymark
Of OpenSAFELY co-morbidities, HD had one of the highest death rates
medrxiv.org/content/10.110…
@Roxytonin @OpenSafely

4/n HD vaccine responses are attenuated. We showed in August 2021: median neutralising antibody titres against Delta after two ChAdOx-1 were <40 [less than range of our assay] in HD patients without prior infection.
thelancet.com/journals/lance…
Tweetorial:

https://twitter.com/bealelab/status/1425948311714926594?s=20

5/n Health care and laboratory workers develop good titres of Omicron neutralising antibodies after 3 doses of BNT162b2

thelancet.com/journals/lance…
Tweetorial:

https://twitter.com/DavidLVBauer/status/1483945351161819140?s=20

6/n … but do HD patients respond as well?

We used live virus microneutralisation assays - developed by @MaryYiWeiWu @DrUlferts Ruth Harvey & Mike Howell - to assess titres before and after dose 3 (median 27days post) 98 patients, 50 sera after dose 3.

https://twitter.com/MaryYiWeiWu/status/1472311359723474947?s=20

7/n Assay published widely, and we know it correlates well with estimates of vaccine efficacy:
elifesciences.org/articles/69317
thelancet.com/journals/lance…
thelancet.com/journals/lance…
thelancet.com/journals/lance…

8/n We found that a dose of BNT162b2 after ChAdOx/ChAdOx or BNT162b2/BNT162b2 increased titres against Delta, likely above the correlate of protection.

9/n Looking at Omicron titres, we found that three doses of BNT162b2 induced neutralising antibodies to a median ~256. For ChAdOx/ChAdOx/BNT162b2 that induction was modest, with a median <40.

10/n Caveat: this is an observational study and the ChAdOx/ChAdOx/BNT162b2 recipients are ~10 years older than the BNT162b2/BNT162b2/BNT162b2.

11/n Some HD patients are immunosuppressed - eg failed renal transplants, or for ongoing autoimmune disease. Excluding immunosuppressed patients from the analysis improved both responses (details in the paper).

12/n In the UK, HD patients are offered 3 doses. A small group - who are immunosuppressed - are already eligible for 4 doses. Our data suggests that eligibility might need to widen.

13/n Team: @MaryYiWeiWu @RBillany @dremmacbw @gavinpaulkelly @CharlesSwanton @LabGandhi @DavidLVBauer @mkwillicombe @DrMattGB @stephenmcadoo @drpaddymark @Sush_Shankar @drmattgb @ronasmi74244228 @salama_alan @rezamotallebov @toomuchaltitude ++ more off Twitter.

14/n Thanks to Gavin Screaton from @OxfordMedSci, who shared an Omicron isolate for distribution by #G2P-UK led by @wendybarclay11.

This is the second 'trailer', feature length to come (1k patients).
And again, thanks to our funders, patients and colleagues.

15/n Huge @TheCrick team and @UKKidney colleagues coordinated by brilliant @EdjCarr, who also wrangled data tirelessly! 👏👏👏