1/Our PITCH consortium preprint on immune responses during different Pfizer BNT162b2 dosing regimens is out! pitch-study.org TL;DR get both doses of whichever vaccine you are offered
2/Led by @rebecca37704429 and @Susannajd with Paul Klenerman and Miles Carroll (not on twitter!)@DHSCgovuk @UKCICstudy @PHE_uk @stephanie200586 @chrisjaduncan @EleanorBarnesOx @AlexRichter3 @sarahlrj @LanceTurtle and more!
3/Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the UK to accelerate population coverage with a single dose. Recruiting 503 healthcare workers across 5 UK centres, we set out to answer some questions...
4)What happens to antibodies and T cells during this “long” interval? 1)Is there a difference in the immune responses after the 2nd Pfizer dose in people getting the “short” (average 3 weeks) compared to “long” (average 10 weeks) dosing regimen?
5/Firstly, to put our results in context, in the @PHE_uk #SIRENstudy led by @SMHopkins sustained protection following a single Pfizer dose was seen in healthcare workers out to 12 weeks. Caveat: this was at a time when the Alpha variant was dominant
6/In #SARSCoV2 naïve people who had “long” interval dosing neutralising antibody levels in blood (using ‘live’ virus by Screaton lab) drop during this interval. By 10 weeks, neutralising activity against the Delta variant is minimal, but a good response is seen after the 2nd dose
7/This is mirrored by binding antibodies (easier to measure than neutralising antibodies) in #SARSCoV2 naïve people (grey). In those previously infected (red), we still see a drop during the “long” interval, but to a lesser extent and antibodies are maintained at a higher level
8/Interestingly (well we thought so as T cell enthusiasts), the T cell response behaved differently and was maintained after 1 dose during this “long” dosing interval in both #SARSCoV2 naïve (grey) and previously infected (red) individuals
9/Does the dosing interval have an impact on your ‘final’ immune response? In #SARSCoV2 naïve people (grey), the ”long” interval results in higher antibody levels after the full course compared to the “short” interval; there is no difference in those previously infected (red)
10/This is mirrored in neutralisation assays, where in #SARSCoV2 naïve people, the “long” interval results in higher neutralising antibodies after the 2nd dose, including against the beta, gamma and delta variants
11/What about T cells? Again, we saw a different pattern to antibodies. The “long” interval did not result in higher T cell responses. In fact, the T cell response after the 2nd dose was slightly lower in SARS-CoV-2 naïve people (grey) receiving the “long” dosing regimen
12/We looked more closely at the character of the T cells and found the “long” interval resulted in more “helper” CD4+ T cells in SARS-CoV-2 naïve people. This may be an important factor in explaining the better antibody responses we see in this group
13/Finally, we looked at what happens over time in #SARSCoV2 naïve people who had the “short” course dosing. Neutralising antibody levels had dropped significantly by week 13 after the 2nd dose…
14/… But T cells were again well maintained over time, just like after a single dose
15/Unlike neutralising antibodies, T cell responses to spike did not demonstrate immune escape for the Delta variant in our assay. Go T cells!
16/Importantly we do not know yet what this means clinically for protection from infection or severe disease over time after the 2nd dose. We also do not know yet whether responses are more durable after “long” interval dosing – we will follow up
17/These immunology results are at a population level, not individual, & there is huge variation in responses. Don’t worry if you got 2 vaccines on a “short” interval – 2 jabs are great! Please accept vaccines when you are offered them
18/Many thanks to the many healthcare workers who took part, @DHSCgovuk who funded the study, plus our other funders @UKCICstudy @UKRI_News @NIHRresearch
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