Thread by @LanceTurtle

Our paper on immune responses to COVID vaccine (mostly Pfizer) in 237 healthcare workers, 124 #SARSCoV2 naïve and 113 previously infected, from the PITCH consortium @pitchstudy is out as a pre-print today.
papers.ssrn.com/sol3/papers.cf…
@pitchstudy
@DHSCgovuk
@UKCICstudy
@PHE_uk
1/16

https://twitter.com/UKCICstudy/status/1375428633343442951

We already know from the @PHE_uk #SIRENstudy that Pfizer vaccine is protective in healthcare workers. In this paper, we investigate possible mechanisms of protection. 2/17

We measured T cell responses to the #SARSCoV2 spike protein, and antibody responses against #SARSCoV2 spike, and also against seasonal human coronaviruses as well.
3/17

We found that:
T cell and antibody responses in naïve people after one dose of vaccine were similar to those in people previously exposed to #SARSCoV2. Data from the @PHE_uk #SIRENstudy suggest that these responses are protective against COVID, which is reassuring. 4/17

Using fresh ELISpots assays done in one centre, T cell responses increase after vaccination, as expected, in both naive and previously #SARSCoV2 infected people. However, the increase in previously infected people was much larger. 5/17

We repeated this using ELISpots from frozen cells that were harmonised across three centres, confirming this result. 6/18

T cell responses in people who were previously exposed to #SARSCoV2 also got broader after a dose of vaccine, suggesting that more parts of the spike protein are recognised. 7/18

Antibody responses also increased much more after vaccination in previously #SARSCoV2 infected people. Naïve people who had two vaccine doses had bigger responses, but they did not catch up with those previously infected, unlike the case for T cell responses. 8/18

Note here that the level of antibody shortly after one dose of vaccine is in fact higher than that in naturally infected people, who were infected about 8-10 months previously. 9/18

The ability of plasma to neutralise live virus and the S. African variant of concern (VOC) were measured. People prev infected with #SARSCoV2 made better neutralising responses against the VOC after one dose of vaccine. Naive people showed no cross neutralising activity. 10/18

These are test tube assays, but there are other components of the immune system that also may be relevant that we have not measured. 11/18

[For the T cell affinionados out there]: T cell responses were mainly seen in CD4+ T cells, with a higher proportion of the response in CD4 than CD8 in previously infected people. 12/18

However, responses were actually more polyfunctional in naive vaccine recipients. P value for this comparison: p = 0.048 13/18

So what does this mean for immunity? This suggests that a single dose of vaccine in naive people generates sufficient immunity to give significant protection, in line with current clinical observations. 14/18

If you have had #COVID19 already, your response is larger to the vaccine. But we don’t know what this means for long term immunity yet. We recommend that people get their second dose, to make sure that everyone gets the best chance of long lasting immunity. 15/18

The caveats to this study are that, compared with effectiveness studies, we studied a relatively small number of people. However, as T cell studies go, this is a large study - big team science here. Also we can’t comment directly on protection here. 16/18

So what about the future? We will be studying this cohort as they get their second vaccine. Because we are nested within the #SIRENstudy, we will also be able to study events of particular interest, like people who have been infected after vaccination, or re-infected. 17/18

Big thank you to all those involved in this work, which was lead by @Thushan_deSilva.
@Susannajd
@EleanorBarnesOx
@ShonaCMoore
@chrisjaduncan
@SMHopkins
@AlexRichter3
With apologies to those whose twitter handles I haven't got or have missed - please add! 18/18

With thanks to the funding and support of @DHSCgovuk and the UK coronavirus immunology consortium @UKCICstudy

@HPRUezi

@livuninews

Thanks to @mugecevik for helping fix the broken thread!!