Tweet
UK Preprint: PITCH study – Antibody & Cellular Immune Responses after Two Different Dosing Schedules of the Pfizer Vaccine
Credit ACIP/CDC
#16,082
One of the reasons why - despite any personal misgivings I might have - I try not to be overly critical of governments and agencies which adopt non-standard approaches (within in reason, of course) to dealing with this pandemic (or any crisis) is that - if everyone follows exactly the same `book' - we may end up overlooking a not-so-obvious better course of action.
I've certainly expressed my reservations (see here, here, here, and here) - sometimes strongly - but I rarely lambast those ideas as completely idiotic.
A prime example comes from the UK, which last week adopted what appears (IMHO) to be a risky strategy to abandon nearly all COVID restrictions (see UK PM: COVID Restrictions To End July 19th), banking on the mitigating impact of vaccines to soften the impact of the pandemic as they open up their economy.
While risky, I accept that we may in fact learn something from this experiment, whichever way it goes.
This isn't the first time the UK has adopted a contrarian approach to the pandemic, and today we may have evidence that one of their earlier decisions - to delay giving the second (booster) shot of the mRNA vaccine until after 8 or 12 weeks, instead of the recommended 3 to 4 - may have produced a better, and longer lasting, immune response.
Their goal was to get as many people partially protected, in as short of time as possible. And when that decision was made (in late 2020), 1 dose of the vaccine appeared to be nearly as effective as being fully vaccinated against the current (Alpha) strain.
As the Delta variant emerged, and became dominant, it became apparent that 1 dose of the vaccine was far less protective, but the UK was already well into delivering booster shots by that time.
Late this week, Israel - which has one of the earliest, and most highly vaccinated populations - announced very low (41%) protection against symptomatic infection by the Delta Variant from the Pfizer vaccine, which is in stark contrast to what the UK has reported (88%).
Local research claims Pfizer shot now only 41% effective against symptomatic COVID, while British stats have it at 88%
Quite notably, Israel originally reported a 90% protection against symptomatic disease, but over the past 6 months, that protection has waned rapidly, with people who received their vaccine in January now estimated to have just 16% protection, while in those vaccinated in April are around 75%.
While there may be other confounders at work, the most obvious difference between the vaccination campaigns in Israel and the UK (and most other countries using Pfizer, including the United States) is the duration between the receipt of the first and second shot; with most countries following the manufacturer's recommended 3-4 week interval.
While data is still emerging, on Friday the UK published a preprint on their "Protective Immunity from T cells to Covid-19 in Health workers" (PITCH) multi-university study, which suggests the longer interval between the first and second mRNA shot increases its effectiveness two-fold.
How long that advantage might last is unknown, but the numbers (so far) are impressive.
First stop, a press release on the preprint.
We studied 503 healthcare workers in Birmingham, Liverpool, Newcastle, Oxford and Sheffield, comparing short (median 3.4 weeks, range 2-5 weeks) and long (median 10 weeks, range 6-14 weeks) dosing schedules of the Pfizer vaccine. This is one of the most comprehensive studies into the immune response to COVID-19 vaccines outside of a clinical trial to date.
We found that for people getting the longer dosing interval, antibodies fell over the 10 weeks after the first dose, but T cell levels were well-maintained. We know that a single dose of vaccine gives significant protection against COVID-19, so T cells may be an important part of the mechanism.
The long dosing interval resulted in 2x higher neutralising antibodies against all variants of the virus tested, including the Delta variant, compared to the short dosing interval. Absolute numbers of T cells to spike were lower after the long interval compared to the short one, but the T cell response had more characteristics of a helper response promoting long term memory and antibody production.
Regardless of the dosing schedule, the study found levels of antibodies and T cells varied from person to person, which may depend on genetics, underlying health conditions, and past exposure to COVID-19 and other viruses. This means our study is more relevant at a population level than for individual people, and underlies the importance of everyone getting two doses of the COVID-19 vaccine to maximise their own protection, particularly against Variants of Concern.
Professor Susanna Dunachie from University of Oxford said:
“Our study aimed to shine a light on the different type of immune cells involved to help us better understand the potential mechanisms of protection, particularly against new Variants of Concern. It is clear from our findings that to maximise your individual protection, it is very important to get two doses of the COVID vaccine when offered”.
We'll need to see if these trends are confirmed in other countries - including the United States - before we can say with any certainty, but if this research holds up, it may signal the need for a third `booster' shot in some countries sooner than many had hoped.
While controversial at the time, the UK's decision to space out their 1st and 2nd vaccine shots may have led us to an important discovery. Time will tell.
You can read the full 22-page preprint at the following link.
Authors Rebecca P. Payne1 *, Stephanie Longet2 *, James A. Austin3 *, Donal T. Skelly4,5,6*, Wanwisa Dejnirattisai2 , Sandra Adele4 , Naomi Meardon7 , Sian Faustini8 , Saly Al-Taei8 , Shona C. Moore3 , Tom Tipton2 , Luisa M Hering3 , Adrienn Angyal9 , Rebecca Brown9 , Natalie Gillson10, Susan L Dobson3 , Ali Amini5,11, Piyada Supasa2 , Andrew Cross1 , Gurjinder Sandhar9 , Jonathan A. Kilby9 , Jessica K Tyerman1 , Alexander R Nicols1 , Thomas Altmann1,12, Hailey Hornsby9 , Rachel Whitham7 , Eloise Phillips4 , Tom Malone4 , Alexander Hargreaves2 , Adrian Shields13, Ayoub Saei10, Sarah Foulkes10, Lizzie Stafford5 , Sile Johnson4,5,14 , Daniel G. Wootton3,15,16 , Christopher P. Conlon5 , Katie Jeffery5 , Philippa C. Matthews4,5, John Frater4,5, Alexandra S. Deeks4,5, Christina Dold17,18 , Andrew J. Pollard17,18 , Anthony Brown4 , Sarah L. Rowland-Jones7 , Juthathip Mongkolsapaya2,19,20, Eleanor Barnes4,5,11,18 , Susan Hopkins10,21,22 , Victoria Hall10,22 , Christopher JA Duncan1,23 †, Alex Richter8,13 †, Miles Carroll2 †, Gavin Screaton2 †, Thushan I. de Silva7,9†, Lance Turtle3,16, †, Paul Klenerman4,5,11,18 †^, Susanna Dunachie4,5,24,25† on behalf of the PITCH Consortium+
If this data holds up (still an `if', as it is based on a small cohort of 503 HCWs) then it suggests the call for fully vaccinated people to continue to wear face masks indoors is well worth heeding, as vaccination protection against symptomatic infection diminishes over time.
So far, the news remains positive regarding the vaccine's protection against severe illness, hospitalization, and death, regardless of the the dosing interval.
Which is why I'm thankful to have both shots, even if their protection isn't 100%.
Credit ACIP/CDC
#16,082
One of the reasons why - despite any personal misgivings I might have - I try not to be overly critical of governments and agencies which adopt non-standard approaches (within in reason, of course) to dealing with this pandemic (or any crisis) is that - if everyone follows exactly the same `book' - we may end up overlooking a not-so-obvious better course of action.
I've certainly expressed my reservations (see here, here, here, and here) - sometimes strongly - but I rarely lambast those ideas as completely idiotic.
A prime example comes from the UK, which last week adopted what appears (IMHO) to be a risky strategy to abandon nearly all COVID restrictions (see UK PM: COVID Restrictions To End July 19th), banking on the mitigating impact of vaccines to soften the impact of the pandemic as they open up their economy.
While risky, I accept that we may in fact learn something from this experiment, whichever way it goes.
This isn't the first time the UK has adopted a contrarian approach to the pandemic, and today we may have evidence that one of their earlier decisions - to delay giving the second (booster) shot of the mRNA vaccine until after 8 or 12 weeks, instead of the recommended 3 to 4 - may have produced a better, and longer lasting, immune response.
Their goal was to get as many people partially protected, in as short of time as possible. And when that decision was made (in late 2020), 1 dose of the vaccine appeared to be nearly as effective as being fully vaccinated against the current (Alpha) strain.
As the Delta variant emerged, and became dominant, it became apparent that 1 dose of the vaccine was far less protective, but the UK was already well into delivering booster shots by that time.
Late this week, Israel - which has one of the earliest, and most highly vaccinated populations - announced very low (41%) protection against symptomatic infection by the Delta Variant from the Pfizer vaccine, which is in stark contrast to what the UK has reported (88%).
Local research claims Pfizer shot now only 41% effective against symptomatic COVID, while British stats have it at 88%
Quite notably, Israel originally reported a 90% protection against symptomatic disease, but over the past 6 months, that protection has waned rapidly, with people who received their vaccine in January now estimated to have just 16% protection, while in those vaccinated in April are around 75%.
While there may be other confounders at work, the most obvious difference between the vaccination campaigns in Israel and the UK (and most other countries using Pfizer, including the United States) is the duration between the receipt of the first and second shot; with most countries following the manufacturer's recommended 3-4 week interval.
While data is still emerging, on Friday the UK published a preprint on their "Protective Immunity from T cells to Covid-19 in Health workers" (PITCH) multi-university study, which suggests the longer interval between the first and second mRNA shot increases its effectiveness two-fold.
How long that advantage might last is unknown, but the numbers (so far) are impressive.
First stop, a press release on the preprint.
July 23rd, 2021
Our latest publication looks at whether the immune response to the Pfizer COVID-19 vaccine is different depending on the number of weeks between the two doses.
Our latest publication looks at whether the immune response to the Pfizer COVID-19 vaccine is different depending on the number of weeks between the two doses.
We studied 503 healthcare workers in Birmingham, Liverpool, Newcastle, Oxford and Sheffield, comparing short (median 3.4 weeks, range 2-5 weeks) and long (median 10 weeks, range 6-14 weeks) dosing schedules of the Pfizer vaccine. This is one of the most comprehensive studies into the immune response to COVID-19 vaccines outside of a clinical trial to date.
We found that for people getting the longer dosing interval, antibodies fell over the 10 weeks after the first dose, but T cell levels were well-maintained. We know that a single dose of vaccine gives significant protection against COVID-19, so T cells may be an important part of the mechanism.
The long dosing interval resulted in 2x higher neutralising antibodies against all variants of the virus tested, including the Delta variant, compared to the short dosing interval. Absolute numbers of T cells to spike were lower after the long interval compared to the short one, but the T cell response had more characteristics of a helper response promoting long term memory and antibody production.
Regardless of the dosing schedule, the study found levels of antibodies and T cells varied from person to person, which may depend on genetics, underlying health conditions, and past exposure to COVID-19 and other viruses. This means our study is more relevant at a population level than for individual people, and underlies the importance of everyone getting two doses of the COVID-19 vaccine to maximise their own protection, particularly against Variants of Concern.
Professor Susanna Dunachie from University of Oxford said:
“Our study aimed to shine a light on the different type of immune cells involved to help us better understand the potential mechanisms of protection, particularly against new Variants of Concern. It is clear from our findings that to maximise your individual protection, it is very important to get two doses of the COVID vaccine when offered”.
We'll need to see if these trends are confirmed in other countries - including the United States - before we can say with any certainty, but if this research holds up, it may signal the need for a third `booster' shot in some countries sooner than many had hoped.
While controversial at the time, the UK's decision to space out their 1st and 2nd vaccine shots may have led us to an important discovery. Time will tell.
You can read the full 22-page preprint at the following link.
Authors Rebecca P. Payne1 *, Stephanie Longet2 *, James A. Austin3 *, Donal T. Skelly4,5,6*, Wanwisa Dejnirattisai2 , Sandra Adele4 , Naomi Meardon7 , Sian Faustini8 , Saly Al-Taei8 , Shona C. Moore3 , Tom Tipton2 , Luisa M Hering3 , Adrienn Angyal9 , Rebecca Brown9 , Natalie Gillson10, Susan L Dobson3 , Ali Amini5,11, Piyada Supasa2 , Andrew Cross1 , Gurjinder Sandhar9 , Jonathan A. Kilby9 , Jessica K Tyerman1 , Alexander R Nicols1 , Thomas Altmann1,12, Hailey Hornsby9 , Rachel Whitham7 , Eloise Phillips4 , Tom Malone4 , Alexander Hargreaves2 , Adrian Shields13, Ayoub Saei10, Sarah Foulkes10, Lizzie Stafford5 , Sile Johnson4,5,14 , Daniel G. Wootton3,15,16 , Christopher P. Conlon5 , Katie Jeffery5 , Philippa C. Matthews4,5, John Frater4,5, Alexandra S. Deeks4,5, Christina Dold17,18 , Andrew J. Pollard17,18 , Anthony Brown4 , Sarah L. Rowland-Jones7 , Juthathip Mongkolsapaya2,19,20, Eleanor Barnes4,5,11,18 , Susan Hopkins10,21,22 , Victoria Hall10,22 , Christopher JA Duncan1,23 †, Alex Richter8,13 †, Miles Carroll2 †, Gavin Screaton2 †, Thushan I. de Silva7,9†, Lance Turtle3,16, †, Paul Klenerman4,5,11,18 †^, Susanna Dunachie4,5,24,25† on behalf of the PITCH Consortium+
If this data holds up (still an `if', as it is based on a small cohort of 503 HCWs) then it suggests the call for fully vaccinated people to continue to wear face masks indoors is well worth heeding, as vaccination protection against symptomatic infection diminishes over time.
So far, the news remains positive regarding the vaccine's protection against severe illness, hospitalization, and death, regardless of the the dosing interval.
Which is why I'm thankful to have both shots, even if their protection isn't 100%.
Comment