Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

PITCH Consortium; Shona C. Moore; Barbara Kronsteiner; Stephanie Longet; Sandra Adele; Alexandra S. Deeks; Chang Liu; Wanwisa Dejnirattisai; Laura Silva Reyes; Naomi Meardon; Sian Faustini; Saly Al-Taei; Tom Tipton; Luisa M. Hering; Adrienn Angyal; Rebecca Brown; Alexander R. Nicols; Susan L. Dobson; Piyada Supasa; Aekkachai Tuekprakhon; Andrew Cross; Jessica K. Tyerman; Hailey Hornsby; Irina Grouneva; Megan Plowright; Peijun Zhang; Thomas A.H. Newman; Jeremy M. Nell; Priyanka Abraham; Mohammad Ali; Tom Malone; Isabel Neale; Eloise Phillips; Joseph D. Wilson; Sam M. Murray; Martha Zewdie; Adrian Shields; Emily C. Horner; Lucy H. Booth; Lizzie Stafford; Sagida Bibi; Daniel G. Wootton; Alexander J. Mentzer; Christopher P. Conlon; Katie Jeffery; Philippa C. Matthews; Andrew J. Pollard; Anthony Brown; Sarah L. Rowland-Jones; Juthathip Mongkolsapaya; Rebecca P. Payne; Christina Dold; Teresa Lambe; James E.D. Thaventhiran; Gavin Screaton; Eleanor Barnes; Susan Hopkins; Victoria Hall; Christopher J.A. Duncan; Alex Richter; Miles Carroll; Thushan I. De Silva; Paul Klenerman; Susanna Dunachie; Lance Turtle; Elena Efstathiou

doi:10.1016/j.medj.2023.02.004

Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

PITCH Consortium
, Shona C. Moore
, Barbara Kronsteiner
, Stephanie Longet
, Sandra Adele
, Alexandra S. Deeks
, Chang Liu
, Wanwisa Dejnirattisai
, Laura Silva Reyes
, Naomi Meardon
, Sian Faustini
, Saly Al-Taei
, Tom Tipton
, Luisa M. Hering
, Adrienn Angyal
, Rebecca Brown
, Alexander R. Nicols
, Susan L. Dobson
, Piyada Supasa
, Aekkachai Tuekprakhon

Andrew Cross, Jessica K. Tyerman, Hailey Hornsby, Irina Grouneva, Megan Plowright, Peijun Zhang, Thomas A.H. Newman, Jeremy M. Nell, Priyanka Abraham, Mohammad Ali, Tom Malone, Isabel Neale, Eloise Phillips, Joseph D. Wilson, Sam M. Murray, Martha Zewdie, Adrian Shields, Emily C. Horner, Lucy H. Booth, Lizzie Stafford, Sagida Bibi, Daniel G. Wootton, Alexander J. Mentzer, Christopher P. Conlon, Katie Jeffery, Philippa C. Matthews, Andrew J. Pollard, Anthony Brown, Sarah L. Rowland-Jones, Juthathip Mongkolsapaya, Rebecca P. Payne, Christina Dold, Teresa Lambe, James E.D. Thaventhiran, Gavin Screaton, Eleanor Barnes, Susan Hopkins, Victoria Hall, Christopher J.A. Duncan, Alex Richter, Miles Carroll, Thushan I. De Silva, Paul Klenerman^*, Susanna Dunachie, Lance Turtle^*, Elena Efstathiou

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses—and hence protection from disease—requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination.

Methods: Here, we report longer follow-up of 684 HCWs in this cohort over 6–9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination.

Findings: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose.

Conclusions: Broadly cross-reactive T cell responses are well maintained over time—especially in those with combined vaccine and infection-induced immunity (“hybrid” immunity)—and may contribute to continued protection against severe disease.

Funding: Department for Health and Social Care, Medical Research Council.

Original language	English
Pages (from-to)	191-215.e9
Number of pages	35
Journal	Med
Volume	4
Issue number	3
Early online date	16 Feb 2023
DOIs	https://doi.org/10.1016/j.medj.2023.02.004
Publication status	Published - 10 Mar 2023

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

SARS-CoV-2
COVID-19
COVID vaccine
T cells
antibody
immunity

Access to Document

10.1016/j.medj.2023.02.004Licence: Creative Commons: Attribution (CC BY)

Investigation of proven vaccine breakthrough by SARS-CoV-2 variants in established UK healthcare worker cohorts: SIREN consortium & PITCH Plus Pathway
Richter, A. (Principal Investigator)
Medical Research Council
13/08/21 → 10/02/23
Project: Research Councils

Cite this

PITCH Consortium, Moore, S. C., Kronsteiner, B., Longet, S., Adele, S., Deeks, A. S., Liu, C., Dejnirattisai, W., Reyes, L. S., Meardon, N., Faustini, S., Al-Taei, S., Tipton, T., Hering, L. M., Angyal, A., Brown, R., Nicols, A. R., Dobson, S. L., Supasa, P., ... Efstathiou, E. (2023). Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens. Med, 4(3), 191-215.e9. https://doi.org/10.1016/j.medj.2023.02.004

@article{1a1c02f0259e4fc9a66e8140420a118b,

title = "Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens",

abstract = "Background: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses—and hence protection from disease—requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. Methods: Here, we report longer follow-up of 684 HCWs in this cohort over 6–9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination. Findings: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose. Conclusions: Broadly cross-reactive T cell responses are well maintained over time—especially in those with combined vaccine and infection-induced immunity (“hybrid” immunity)—and may contribute to continued protection against severe disease. Funding: Department for Health and Social Care, Medical Research Council.",

keywords = "SARS-CoV-2, COVID-19, COVID vaccine, T cells, antibody, immunity",

author = "\{PITCH Consortium\} and Moore, \{Shona C.\} and Barbara Kronsteiner and Stephanie Longet and Sandra Adele and Deeks, \{Alexandra S.\} and Chang Liu and Wanwisa Dejnirattisai and Reyes, \{Laura Silva\} and Naomi Meardon and Sian Faustini and Saly Al-Taei and Tom Tipton and Hering, \{Luisa M.\} and Adrienn Angyal and Rebecca Brown and Nicols, \{Alexander R.\} and Dobson, \{Susan L.\} and Piyada Supasa and Aekkachai Tuekprakhon and Andrew Cross and Tyerman, \{Jessica K.\} and Hailey Hornsby and Irina Grouneva and Megan Plowright and Peijun Zhang and Newman, \{Thomas A.H.\} and Nell, \{Jeremy M.\} and Priyanka Abraham and Mohammad Ali and Tom Malone and Isabel Neale and Eloise Phillips and Wilson, \{Joseph D.\} and Murray, \{Sam M.\} and Martha Zewdie and Adrian Shields and Horner, \{Emily C.\} and Booth, \{Lucy H.\} and Lizzie Stafford and Sagida Bibi and Wootton, \{Daniel G.\} and Mentzer, \{Alexander J.\} and Conlon, \{Christopher P.\} and Katie Jeffery and Matthews, \{Philippa C.\} and Pollard, \{Andrew J.\} and Anthony Brown and Rowland-Jones, \{Sarah L.\} and Juthathip Mongkolsapaya and Payne, \{Rebecca P.\} and Christina Dold and Teresa Lambe and Thaventhiran, \{James E.D.\} and Gavin Screaton and Eleanor Barnes and Susan Hopkins and Victoria Hall and Duncan, \{Christopher J.A.\} and Alex Richter and Miles Carroll and \{De Silva\}, \{Thushan I.\} and Paul Klenerman and Susanna Dunachie and Lance Turtle and Elena Efstathiou",

year = "2023",

month = mar,

day = "10",

doi = "10.1016/j.medj.2023.02.004",

language = "English",

volume = "4",

pages = "191--215.e9",

journal = "Med",

issn = "2666-6359",

publisher = "Cell Press",

number = "3",

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PITCH Consortium, Moore, SC, Kronsteiner, B, Longet, S, Adele, S, Deeks, AS, Liu, C, Dejnirattisai, W, Reyes, LS, Meardon, N, Faustini, S, Al-Taei, S, Tipton, T, Hering, LM, Angyal, A, Brown, R, Nicols, AR, Dobson, SL, Supasa, P, Tuekprakhon, A, Cross, A, Tyerman, JK, Hornsby, H, Grouneva, I, Plowright, M, Zhang, P, Newman, TAH, Nell, JM, Abraham, P, Ali, M, Malone, T, Neale, I, Phillips, E, Wilson, JD, Murray, SM, Zewdie, M, Shields, A, Horner, EC, Booth, LH, Stafford, L, Bibi, S, Wootton, DG, Mentzer, AJ, Conlon, CP, Jeffery, K, Matthews, PC, Pollard, AJ, Brown, A, Rowland-Jones, SL, Mongkolsapaya, J, Payne, RP, Dold, C, Lambe, T, Thaventhiran, JED, Screaton, G, Barnes, E, Hopkins, S, Hall, V, Duncan, CJA, Richter, A, Carroll, M, De Silva, TI, Klenerman, P, Dunachie, S, Turtle, L & Efstathiou, E 2023, 'Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens', Med, vol. 4, no. 3, pp. 191-215.e9. https://doi.org/10.1016/j.medj.2023.02.004

TY - JOUR

T1 - Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

AU - PITCH Consortium

AU - Moore, Shona C.

AU - Kronsteiner, Barbara

AU - Longet, Stephanie

AU - Adele, Sandra

AU - Deeks, Alexandra S.

AU - Liu, Chang

AU - Dejnirattisai, Wanwisa

AU - Reyes, Laura Silva

AU - Meardon, Naomi

AU - Faustini, Sian

AU - Al-Taei, Saly

AU - Tipton, Tom

AU - Hering, Luisa M.

AU - Angyal, Adrienn

AU - Brown, Rebecca

AU - Nicols, Alexander R.

AU - Dobson, Susan L.

AU - Supasa, Piyada

AU - Tuekprakhon, Aekkachai

AU - Cross, Andrew

AU - Tyerman, Jessica K.

AU - Hornsby, Hailey

AU - Grouneva, Irina

AU - Plowright, Megan

AU - Zhang, Peijun

AU - Newman, Thomas A.H.

AU - Nell, Jeremy M.

AU - Abraham, Priyanka

AU - Ali, Mohammad

AU - Malone, Tom

AU - Neale, Isabel

AU - Phillips, Eloise

AU - Wilson, Joseph D.

AU - Murray, Sam M.

AU - Zewdie, Martha

AU - Shields, Adrian

AU - Horner, Emily C.

AU - Booth, Lucy H.

AU - Stafford, Lizzie

AU - Bibi, Sagida

AU - Wootton, Daniel G.

AU - Mentzer, Alexander J.

AU - Conlon, Christopher P.

AU - Jeffery, Katie

AU - Matthews, Philippa C.

AU - Pollard, Andrew J.

AU - Brown, Anthony

AU - Rowland-Jones, Sarah L.

AU - Mongkolsapaya, Juthathip

AU - Payne, Rebecca P.

AU - Dold, Christina

AU - Lambe, Teresa

AU - Thaventhiran, James E.D.

AU - Screaton, Gavin

AU - Barnes, Eleanor

AU - Hopkins, Susan

AU - Hall, Victoria

AU - Duncan, Christopher J.A.

AU - Richter, Alex

AU - Carroll, Miles

AU - De Silva, Thushan I.

AU - Klenerman, Paul

AU - Dunachie, Susanna

AU - Turtle, Lance

AU - Efstathiou, Elena

PY - 2023/3/10

Y1 - 2023/3/10

N2 - Background: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses—and hence protection from disease—requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. Methods: Here, we report longer follow-up of 684 HCWs in this cohort over 6–9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination. Findings: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose. Conclusions: Broadly cross-reactive T cell responses are well maintained over time—especially in those with combined vaccine and infection-induced immunity (“hybrid” immunity)—and may contribute to continued protection against severe disease. Funding: Department for Health and Social Care, Medical Research Council.

AB - Background: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses—and hence protection from disease—requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. Methods: Here, we report longer follow-up of 684 HCWs in this cohort over 6–9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination. Findings: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose. Conclusions: Broadly cross-reactive T cell responses are well maintained over time—especially in those with combined vaccine and infection-induced immunity (“hybrid” immunity)—and may contribute to continued protection against severe disease. Funding: Department for Health and Social Care, Medical Research Council.

KW - SARS-CoV-2

KW - COVID-19

KW - COVID vaccine

KW - T cells

KW - antibody

KW - immunity

U2 - 10.1016/j.medj.2023.02.004

DO - 10.1016/j.medj.2023.02.004

M3 - Article

SN - 2666-6359

VL - 4

SP - 191-215.e9

JO - Med

JF - Med

IS - 3

ER -

Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

Abstract

UN SDGs

Keywords

Access to Document

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Projects

Investigation of proven vaccine breakthrough by SARS-CoV-2 variants in established UK healthcare worker cohorts: SIREN consortium & PITCH Plus Pathway

Cite this