Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

PITCH Consortium; Rebecca P. Payne; Stephanie Longet; James A. Austin; Donal T. Skelly; Wanwisa Dejnirattisai; Sandra Adele; Naomi Meardon; Sian Faustini; Saly Al-Taei; Shona C. Moore; Tom Tipton; Luisa M. Hering; Adrienn Angyal; Rebecca Brown; Alexander R. Nicols; Natalie Gillson; Susan L. Dobson; Ali Amini; Piyada Supasa; Andrew Cross; Alice Bridges-Webb; Laura Silva Reyes; Aline Linder; Gurjinder Sandhar; Jonathan A. Kilby; Jessica K. Tyerman; Thomas Altmann; Hailey Hornsby; Rachel Whitham; Eloise Phillips; Tom Malone; Alexander Hargreaves; Adrian Shields; Ayoub Saei; Sarah Foulkes; Lizzie Stafford; Sile Johnson; Daniel G. Wootton; Christopher P. Conlon; Katie Jeffery; Philippa C. Matthews; John Frater; Alexandra S. Deeks; Andrew J. Pollard; Anthony Brown; Sarah L. Rowland-Jones; Juthathip Mongkolsapaya; Eleanor Barnes; Susan Hopkins; Victoria Hall; Christina Dold; Christopher J.A. Duncan; Alex Richter; Miles Carroll; Gavin Screaton; Thushan I. de Silva; Lance Turtle; Paul Klenerman; Susanna Dunachie

doi:10.1016/j.cell.2021.10.011

Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

PITCH Consortium, Rebecca P. Payne^*, Stephanie Longet, James A. Austin, Donal T. Skelly, Wanwisa Dejnirattisai, Sandra Adele, Naomi Meardon, Sian Faustini, Saly Al-Taei, Shona C. Moore, Tom Tipton, Luisa M. Hering, Adrienn Angyal, Rebecca Brown, Alexander R. Nicols, Natalie Gillson, Susan L. Dobson, Ali Amini, Piyada SupasaAndrew Cross, Alice Bridges-Webb, Laura Silva Reyes, Aline Linder, Gurjinder Sandhar, Jonathan A. Kilby, Jessica K. Tyerman, Thomas Altmann, Hailey Hornsby, Rachel Whitham, Eloise Phillips, Tom Malone, Alexander Hargreaves, Adrian Shields, Ayoub Saei, Sarah Foulkes, Lizzie Stafford, Sile Johnson, Daniel G. Wootton, Christopher P. Conlon, Katie Jeffery, Philippa C. Matthews, John Frater, Alexandra S. Deeks, Andrew J. Pollard, Anthony Brown, Sarah L. Rowland-Jones, Juthathip Mongkolsapaya, Eleanor Barnes, Susan Hopkins, Victoria Hall, Christina Dold, Christopher J.A. Duncan, Alex Richter, Miles Carroll, Gavin Screaton, Thushan I. de Silva, Lance Turtle, Paul Klenerman^*, Susanna Dunachie

^*Corresponding author for this work

Immunology and Immunotherapy

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Abstract

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4⁺ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.

Original language	English
Pages (from-to)	5699-5714.e11
Number of pages	27
Journal	Cell
Volume	184
Issue number	23
Early online date	16 Oct 2021
DOIs	https://doi.org/10.1016/j.cell.2021.10.011
Publication status	Published - 11 Nov 2021

Keywords

SARS-CoV-2
COVID-19
vaccine
BNT162b2
antibody
neutralization
B cell
T cell
dosing interval
variants of concern

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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PayneR2021ImmunogenicityFinal published version, 5.04 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

PITCH Consortium, Payne, R. P., Longet, S., Austin, J. A., Skelly, D. T., Dejnirattisai, W., Adele, S., Meardon, N., Faustini, S., Al-Taei, S., Moore, S. C., Tipton, T., Hering, L. M., Angyal, A., Brown, R., Nicols, A. R., Gillson, N., Dobson, S. L., Amini, A., ... Dunachie, S. (2021). Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine. Cell, 184(23), 5699-5714.e11. https://doi.org/10.1016/j.cell.2021.10.011

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title = "Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine",

abstract = "Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.",

keywords = "SARS-CoV-2, COVID-19, vaccine, BNT162b2, antibody, neutralization, B cell, T cell, dosing interval, variants of concern",

author = "{PITCH Consortium} and Payne, {Rebecca P.} and Stephanie Longet and Austin, {James A.} and Skelly, {Donal T.} and Wanwisa Dejnirattisai and Sandra Adele and Naomi Meardon and Sian Faustini and Saly Al-Taei and Moore, {Shona C.} and Tom Tipton and Hering, {Luisa M.} and Adrienn Angyal and Rebecca Brown and Nicols, {Alexander R.} and Natalie Gillson and Dobson, {Susan L.} and Ali Amini and Piyada Supasa and Andrew Cross and Alice Bridges-Webb and Reyes, {Laura Silva} and Aline Linder and Gurjinder Sandhar and Kilby, {Jonathan A.} and Tyerman, {Jessica K.} and Thomas Altmann and Hailey Hornsby and Rachel Whitham and Eloise Phillips and Tom Malone and Alexander Hargreaves and Adrian Shields and Ayoub Saei and Sarah Foulkes and Lizzie Stafford and Sile Johnson and Wootton, {Daniel G.} and Conlon, {Christopher P.} and Katie Jeffery and Matthews, {Philippa C.} and John Frater and Deeks, {Alexandra S.} and Pollard, {Andrew J.} and Anthony Brown and Rowland-Jones, {Sarah L.} and Juthathip Mongkolsapaya and Eleanor Barnes and Susan Hopkins and Victoria Hall and Christina Dold and Duncan, {Christopher J.A.} and Alex Richter and Miles Carroll and Gavin Screaton and {de Silva}, {Thushan I.} and Lance Turtle and Paul Klenerman and Susanna Dunachie",

year = "2021",

month = nov,

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doi = "10.1016/j.cell.2021.10.011",

language = "English",

volume = "184",

pages = "5699--5714.e11",

journal = "Cell",

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number = "23",

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PITCH Consortium, Payne, RP, Longet, S, Austin, JA, Skelly, DT, Dejnirattisai, W, Adele, S, Meardon, N, Faustini, S, Al-Taei, S, Moore, SC, Tipton, T, Hering, LM, Angyal, A, Brown, R, Nicols, AR, Gillson, N, Dobson, SL, Amini, A, Supasa, P, Cross, A, Bridges-Webb, A, Reyes, LS, Linder, A, Sandhar, G, Kilby, JA, Tyerman, JK, Altmann, T, Hornsby, H, Whitham, R, Phillips, E, Malone, T, Hargreaves, A, Shields, A, Saei, A, Foulkes, S, Stafford, L, Johnson, S, Wootton, DG, Conlon, CP, Jeffery, K, Matthews, PC, Frater, J, Deeks, AS, Pollard, AJ, Brown, A, Rowland-Jones, SL, Mongkolsapaya, J, Barnes, E, Hopkins, S, Hall, V, Dold, C, Duncan, CJA, Richter, A, Carroll, M, Screaton, G, de Silva, TI, Turtle, L, Klenerman, P & Dunachie, S 2021, 'Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine', Cell, vol. 184, no. 23, pp. 5699-5714.e11. https://doi.org/10.1016/j.cell.2021.10.011

TY - JOUR

T1 - Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

AU - PITCH Consortium

AU - Payne, Rebecca P.

AU - Longet, Stephanie

AU - Austin, James A.

AU - Skelly, Donal T.

AU - Dejnirattisai, Wanwisa

AU - Adele, Sandra

AU - Meardon, Naomi

AU - Faustini, Sian

AU - Al-Taei, Saly

AU - Moore, Shona C.

AU - Tipton, Tom

AU - Hering, Luisa M.

AU - Angyal, Adrienn

AU - Brown, Rebecca

AU - Nicols, Alexander R.

AU - Gillson, Natalie

AU - Dobson, Susan L.

AU - Amini, Ali

AU - Supasa, Piyada

AU - Cross, Andrew

AU - Bridges-Webb, Alice

AU - Reyes, Laura Silva

AU - Linder, Aline

AU - Sandhar, Gurjinder

AU - Kilby, Jonathan A.

AU - Tyerman, Jessica K.

AU - Altmann, Thomas

AU - Hornsby, Hailey

AU - Whitham, Rachel

AU - Phillips, Eloise

AU - Malone, Tom

AU - Hargreaves, Alexander

AU - Shields, Adrian

AU - Saei, Ayoub

AU - Foulkes, Sarah

AU - Stafford, Lizzie

AU - Johnson, Sile

AU - Wootton, Daniel G.

AU - Conlon, Christopher P.

AU - Jeffery, Katie

AU - Matthews, Philippa C.

AU - Frater, John

AU - Deeks, Alexandra S.

AU - Pollard, Andrew J.

AU - Brown, Anthony

AU - Rowland-Jones, Sarah L.

AU - Mongkolsapaya, Juthathip

AU - Barnes, Eleanor

AU - Hopkins, Susan

AU - Hall, Victoria

AU - Dold, Christina

AU - Duncan, Christopher J.A.

AU - Richter, Alex

AU - Carroll, Miles

AU - Screaton, Gavin

AU - de Silva, Thushan I.

AU - Turtle, Lance

AU - Klenerman, Paul

AU - Dunachie, Susanna

PY - 2021/11/11

Y1 - 2021/11/11

N2 - Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.

AB - Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.

KW - SARS-CoV-2

KW - COVID-19

KW - vaccine

KW - BNT162b2

KW - antibody

KW - neutralization

KW - B cell

KW - T cell

KW - dosing interval

KW - variants of concern

U2 - 10.1016/j.cell.2021.10.011

DO - 10.1016/j.cell.2021.10.011

M3 - Article

SN - 0092-8674

VL - 184

SP - 5699-5714.e11

JO - Cell

JF - Cell

IS - 23

ER -