Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants

COVIDsortium immune correlates network; COVIDsortium investigators; Catherine J. Reynolds; Joseph M. Gibbons; Corinna Pade; Kai Min Lin; Diana Muñoz Sandoval; Franziska Pieper; David K. Butler; Siyi Liu; Ashley D. Otter; George Joy; Katia Menacho; Marianna Fontana; Angelique Smit; Beatrix Kele; Teresa Cutino-Mogue; Mala K. Maini; Mahdad Noursadeghi; Tim Brooks; Amanda Semper; Charlotte Manisty; Thomas A. Treibel; James C. Moon; Áine McKnight; Daniel M. Altmann; Rosemary J. Boyton

doi:10.1126/science.abm0811

Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants

COVIDsortium immune correlates network, COVIDsortium investigators, Catherine J. Reynolds, Joseph M. Gibbons, Corinna Pade, Kai Min Lin, Diana Muñoz Sandoval, Franziska Pieper, David K. Butler, Siyi Liu, Ashley D. Otter, George Joy, Katia Menacho, Marianna Fontana, Angelique Smit, Beatrix Kele, Teresa Cutino-Mogue, Mala K. Maini, Mahdad Noursadeghi, Tim BrooksAmanda Semper, Charlotte Manisty, Thomas A. Treibel, James C. Moon, Áine McKnight, Daniel M. Altmann, Rosemary J. Boyton^*

^*Corresponding author for this work

UK Health Security Agency

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Abstract

The impact of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOCs) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection plus two vaccine doses), S1 antibody, memory B cells, and heterologous neutralization of B.1.351, P.1, and B.1.617.2 plateaued, whereas B.1.1.7 neutralization and spike T cell responses increased. Serology using the Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over the 5 months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.

Original language	English
Pages (from-to)	183-192
Number of pages	10
Journal	Science
Volume	375
Issue number	6577
Early online date	2 Dec 2021
DOIs	https://doi.org/10.1126/science.abm0811
Publication status	Published - 14 Jan 2022

Bibliographical note

Funding Information: R.J.B. and D.M.A. are supported by the Medical Research Council (MRC) (grants MR/S019553/1, MR/R02622X/1, MR/V036939/1, and MR/W020610/1), the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC): ITMAT, Cystic Fibrosis Trust SRC (grant 2019SRC015), NIHR EME Fast Track (grant NIHR134607), NIHR Long Covid (grant COV-LT2-0027), Innovate UK (grant SBRI 10008614), and Horizon 2020 Marie Skłodowska-Curie Innovative Training Network (ITN) European Training Network (grant 860325). Á.M. is supported by the MRC (grant MR/W020610/1), NIHR EME Fast Track (grant NIHR134607), Rosetrees Trust, The John Black Charitable Foundation, and Medical College of St Bartholomew’s Hospital Trust. The COVIDsortium is supported by funding donated by individuals, charitable Trusts, and corporations including Goldman Sachs, K. C. Griffin, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from UCLH Charity. Wider support is acknowledged on the COVIDsortium website. Institutional support from Barts Health NHS Trust and Royal Free NHS Foundation Trust facilitated study processes, in partnership with University College London and Queen Mary University of London. MKM is supported by UKRI/NIHR UK-CIC, Wellcome Trust Investigator Award (214191/Z/18/Z) and CRUK Immunology grant (26603). J.C.M., C.M., and T.A.T. are directly and indirectly supported by the University College London Hospitals (UCLH) and Barts NIHR Biomedical Research Centres and through the British Heart Foundation (BHF) (accelerator award AA/18/6/34223). T.T. is funded by a BHF Intermediate Research Fellowship (FS/19/35/34374). MN is supported by the Wellcome Trust (grant 207511/Z/17/Z) and by NIHR Biomedical Research Funding to UCL and UCLH. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

R.J.B. and D.M.A. are members of the Global T cell Expert Consortium and have consulted for Oxford Immunotec outside the submitted work. The remaining authors declare no competing interests.

Open Access: This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.

Publisher Copyright: © 2022 American Association for the Advancement of Science. All rights reserved.

Citation: Reynolds, Catherine J., et al. "Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants." Science (2021): eabm0811.

DOI: 10.1126/science.abm0811

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Cite this

COVIDsortium immune correlates network, COVIDsortium investigators, Reynolds, C. J., Gibbons, J. M., Pade, C., Lin, K. M., Sandoval, D. M., Pieper, F., Butler, D. K., Liu, S., Otter, A. D., Joy, G., Menacho, K., Fontana, M., Smit, A., Kele, B., Cutino-Mogue, T., Maini, M. K., Noursadeghi, M., ... Boyton, R. J. (2022). Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants. Science, 375(6577), 183-192. https://doi.org/10.1126/science.abm0811

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title = "Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants",

abstract = "The impact of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOCs) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection plus two vaccine doses), S1 antibody, memory B cells, and heterologous neutralization of B.1.351, P.1, and B.1.617.2 plateaued, whereas B.1.1.7 neutralization and spike T cell responses increased. Serology using the Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over the 5 months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.",

author = "{COVIDsortium immune correlates network} and {COVIDsortium investigators} and Reynolds, {Catherine J.} and Gibbons, {Joseph M.} and Corinna Pade and Lin, {Kai Min} and Sandoval, {Diana Mu{\~n}oz} and Franziska Pieper and Butler, {David K.} and Siyi Liu and Otter, {Ashley D.} and George Joy and Katia Menacho and Marianna Fontana and Angelique Smit and Beatrix Kele and Teresa Cutino-Mogue and Maini, {Mala K.} and Mahdad Noursadeghi and Tim Brooks and Amanda Semper and Charlotte Manisty and Treibel, {Thomas A.} and Moon, {James C.} and {\'A}ine McKnight and Altmann, {Daniel M.} and Boyton, {Rosemary J.}",

note = "Funding Information: R.J.B. and D.M.A. are supported by the Medical Research Council (MRC) (grants MR/S019553/1, MR/R02622X/1, MR/V036939/1, and MR/W020610/1), the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC): ITMAT, Cystic Fibrosis Trust SRC (grant 2019SRC015), NIHR EME Fast Track (grant NIHR134607), NIHR Long Covid (grant COV-LT2-0027), Innovate UK (grant SBRI 10008614), and Horizon 2020 Marie Sk{\l}odowska-Curie Innovative Training Network (ITN) European Training Network (grant 860325). {\'A}.M. is supported by the MRC (grant MR/W020610/1), NIHR EME Fast Track (grant NIHR134607), Rosetrees Trust, The John Black Charitable Foundation, and Medical College of St Bartholomew{\textquoteright}s Hospital Trust. The COVIDsortium is supported by funding donated by individuals, charitable Trusts, and corporations including Goldman Sachs, K. C. Griffin, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from UCLH Charity. Wider support is acknowledged on the COVIDsortium website. Institutional support from Barts Health NHS Trust and Royal Free NHS Foundation Trust facilitated study processes, in partnership with University College London and Queen Mary University of London. MKM is supported by UKRI/NIHR UK-CIC, Wellcome Trust Investigator Award (214191/Z/18/Z) and CRUK Immunology grant (26603). J.C.M., C.M., and T.A.T. are directly and indirectly supported by the University College London Hospitals (UCLH) and Barts NIHR Biomedical Research Centres and through the British Heart Foundation (BHF) (accelerator award AA/18/6/34223). T.T. is funded by a BHF Intermediate Research Fellowship (FS/19/35/34374). MN is supported by the Wellcome Trust (grant 207511/Z/17/Z) and by NIHR Biomedical Research Funding to UCL and UCLH. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. R.J.B. and D.M.A. are members of the Global T cell Expert Consortium and have consulted for Oxford Immunotec outside the submitted work. The remaining authors declare no competing interests. Open Access: This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material. Publisher Copyright: {\textcopyright} 2022 American Association for the Advancement of Science. All rights reserved. Citation: Reynolds, Catherine J., et al. {"}Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants.{"} Science (2021): eabm0811. DOI: 10.1126/science.abm0811",

year = "2022",

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doi = "10.1126/science.abm0811",

language = "English",

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COVIDsortium immune correlates network, COVIDsortium investigators, Reynolds, CJ, Gibbons, JM, Pade, C, Lin, KM, Sandoval, DM, Pieper, F, Butler, DK, Liu, S, Otter, AD, Joy, G, Menacho, K, Fontana, M, Smit, A, Kele, B, Cutino-Mogue, T, Maini, MK, Noursadeghi, M, Brooks, T , Semper, A, Manisty, C, Treibel, TA, Moon, JC, McKnight, Á, Altmann, DM & Boyton, RJ 2022, 'Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants', Science, vol. 375, no. 6577, pp. 183-192. https://doi.org/10.1126/science.abm0811

TY - JOUR

T1 - Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants

AU - COVIDsortium immune correlates network

AU - COVIDsortium investigators

AU - Reynolds, Catherine J.

AU - Gibbons, Joseph M.

AU - Pade, Corinna

AU - Lin, Kai Min

AU - Sandoval, Diana Muñoz

AU - Pieper, Franziska

AU - Butler, David K.

AU - Liu, Siyi

AU - Otter, Ashley D.

AU - Joy, George

AU - Menacho, Katia

AU - Fontana, Marianna

AU - Smit, Angelique

AU - Kele, Beatrix

AU - Cutino-Mogue, Teresa

AU - Maini, Mala K.

AU - Noursadeghi, Mahdad

AU - Brooks, Tim

AU - Semper, Amanda

AU - Manisty, Charlotte

AU - Treibel, Thomas A.

AU - Moon, James C.

AU - McKnight, Áine

AU - Altmann, Daniel M.

AU - Boyton, Rosemary J.

N1 - Funding Information: R.J.B. and D.M.A. are supported by the Medical Research Council (MRC) (grants MR/S019553/1, MR/R02622X/1, MR/V036939/1, and MR/W020610/1), the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC): ITMAT, Cystic Fibrosis Trust SRC (grant 2019SRC015), NIHR EME Fast Track (grant NIHR134607), NIHR Long Covid (grant COV-LT2-0027), Innovate UK (grant SBRI 10008614), and Horizon 2020 Marie Skłodowska-Curie Innovative Training Network (ITN) European Training Network (grant 860325). Á.M. is supported by the MRC (grant MR/W020610/1), NIHR EME Fast Track (grant NIHR134607), Rosetrees Trust, The John Black Charitable Foundation, and Medical College of St Bartholomew’s Hospital Trust. The COVIDsortium is supported by funding donated by individuals, charitable Trusts, and corporations including Goldman Sachs, K. C. Griffin, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from UCLH Charity. Wider support is acknowledged on the COVIDsortium website. Institutional support from Barts Health NHS Trust and Royal Free NHS Foundation Trust facilitated study processes, in partnership with University College London and Queen Mary University of London. MKM is supported by UKRI/NIHR UK-CIC, Wellcome Trust Investigator Award (214191/Z/18/Z) and CRUK Immunology grant (26603). J.C.M., C.M., and T.A.T. are directly and indirectly supported by the University College London Hospitals (UCLH) and Barts NIHR Biomedical Research Centres and through the British Heart Foundation (BHF) (accelerator award AA/18/6/34223). T.T. is funded by a BHF Intermediate Research Fellowship (FS/19/35/34374). MN is supported by the Wellcome Trust (grant 207511/Z/17/Z) and by NIHR Biomedical Research Funding to UCL and UCLH. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. R.J.B. and D.M.A. are members of the Global T cell Expert Consortium and have consulted for Oxford Immunotec outside the submitted work. The remaining authors declare no competing interests. Open Access: This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material. Publisher Copyright: © 2022 American Association for the Advancement of Science. All rights reserved. Citation: Reynolds, Catherine J., et al. "Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants." Science (2021): eabm0811. DOI: 10.1126/science.abm0811

PY - 2022/1/14

Y1 - 2022/1/14

N2 - The impact of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOCs) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection plus two vaccine doses), S1 antibody, memory B cells, and heterologous neutralization of B.1.351, P.1, and B.1.617.2 plateaued, whereas B.1.1.7 neutralization and spike T cell responses increased. Serology using the Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over the 5 months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.

AB - The impact of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOCs) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection plus two vaccine doses), S1 antibody, memory B cells, and heterologous neutralization of B.1.351, P.1, and B.1.617.2 plateaued, whereas B.1.1.7 neutralization and spike T cell responses increased. Serology using the Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over the 5 months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.

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U2 - 10.1126/science.abm0811

DO - 10.1126/science.abm0811

M3 - Article

AN - SCOPUS:85122960037

SN - 0036-8075

VL - 375

SP - 183

EP - 192

JO - Science

JF - Science

IS - 6577

ER -

Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants

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