Immunological imprinting of humoral immunity to SARS-CoV-2 in children

Alexander C. Dowell; Tara Lancaster; Rachel Bruton; Georgina Ireland; Christopher Bentley; Panagiota Sylla; Jianmin Zuo; Sam Scott; Azar Jadir; Jusnara Begum; Thomas Roberts; Christine Stephens; Shabana Ditta; Rebecca Shepherdson; Annabel A. Powell; Andrew J. Brent; Bernadette Brent; Frances Baawuah; Ifeanyichukwu Okike; Joanne Beckmann; Shazaad Ahmad; Felicity Aiano; Joanna Garstang; Mary E. Ramsay; Rafaq Azad; Dagmar Waiblinger; Brian Willett; John Wright; Shamez N. Ladhani; Paul Moss

doi:10.1038/s41467-023-39575-2

Immunological imprinting of humoral immunity to SARS-CoV-2 in children

Alexander C. Dowell, Tara Lancaster, Rachel Bruton, Georgina Ireland, Christopher Bentley, Panagiota Sylla, Jianmin Zuo, Sam Scott, Azar Jadir, Jusnara Begum, Thomas Roberts, Christine Stephens, Shabana Ditta, Rebecca Shepherdson, Annabel A. Powell, Andrew J. Brent, Bernadette Brent, Frances Baawuah, Ifeanyichukwu Okike, Joanne BeckmannShazaad Ahmad, Felicity Aiano, Joanna Garstang, Mary E. Ramsay, Rafaq Azad, Dagmar Waiblinger, Brian Willett, John Wright, Shamez N. Ladhani^*, Paul Moss^*

^*Corresponding author for this work

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

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Abstract

Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.

Original language	English
Article number	3845
Number of pages	9
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-39575-2
Publication status	Published - 29 Jun 2023

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10.1038/s41467-023-39575-2Licence: Creative Commons: Attribution (CC BY)

DowellA2023ImmunologicalFinal published version, 1.2 MBLicence: Creative Commons: Attribution (CC BY)

COVID-19 Immunity - National Core Study (IMM-NCS)
Moss, P. (Principal Investigator)
Medical Research Council
1/10/20 → 31/03/21
Project: Research Councils
A UK underpinning platform to study immunology and immunopathology of COVID-19:The UK Coronavirus Immunology Consortium
Duggal, N. (Researcher), Zuo, J. (Researcher), Moss, P. (Principal Investigator), Long, H. (Researcher), Lord, J. (Researcher), Taylor, G. (Researcher) & Wraith, D. (Researcher)
Medical Research Council
20/08/20 → 31/10/22
Project: Research Councils

Cite this

Dowell, A. C., Lancaster, T., Bruton, R., Ireland, G., Bentley, C., Sylla, P., Zuo, J., Scott, S., Jadir, A., Begum, J., Roberts, T., Stephens, C., Ditta, S., Shepherdson, R., Powell, A. A., Brent, A. J., Brent, B., Baawuah, F., Okike, I., ... Moss, P. (2023). Immunological imprinting of humoral immunity to SARS-CoV-2 in children. Nature Communications, 14(1), Article 3845. https://doi.org/10.1038/s41467-023-39575-2

@article{be90f2e35bb841af8301adf08107cbbc,

title = "Immunological imprinting of humoral immunity to SARS-CoV-2 in children",

abstract = "Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.",

author = "Dowell, {Alexander C.} and Tara Lancaster and Rachel Bruton and Georgina Ireland and Christopher Bentley and Panagiota Sylla and Jianmin Zuo and Sam Scott and Azar Jadir and Jusnara Begum and Thomas Roberts and Christine Stephens and Shabana Ditta and Rebecca Shepherdson and Powell, {Annabel A.} and Brent, {Andrew J.} and Bernadette Brent and Frances Baawuah and Ifeanyichukwu Okike and Joanne Beckmann and Shazaad Ahmad and Felicity Aiano and Joanna Garstang and Ramsay, {Mary E.} and Rafaq Azad and Dagmar Waiblinger and Brian Willett and John Wright and Ladhani, {Shamez N.} and Paul Moss",

year = "2023",

month = jun,

day = "29",

doi = "10.1038/s41467-023-39575-2",

language = "English",

volume = "14",

journal = "Nature Communications",

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Dowell, AC , Lancaster, T , Bruton, R, Ireland, G, Bentley, C, Sylla, P, Zuo, J, Scott, S, Jadir, A, Begum, J, Roberts, T, Stephens, C, Ditta, S, Shepherdson, R, Powell, AA, Brent, AJ, Brent, B, Baawuah, F, Okike, I, Beckmann, J, Ahmad, S, Aiano, F, Garstang, J, Ramsay, ME, Azad, R, Waiblinger, D, Willett, B, Wright, J, Ladhani, SN & Moss, P 2023, 'Immunological imprinting of humoral immunity to SARS-CoV-2 in children', Nature Communications, vol. 14, no. 1, 3845. https://doi.org/10.1038/s41467-023-39575-2

TY - JOUR

T1 - Immunological imprinting of humoral immunity to SARS-CoV-2 in children

AU - Dowell, Alexander C.

AU - Lancaster, Tara

AU - Bruton, Rachel

AU - Ireland, Georgina

AU - Bentley, Christopher

AU - Sylla, Panagiota

AU - Zuo, Jianmin

AU - Scott, Sam

AU - Jadir, Azar

AU - Begum, Jusnara

AU - Roberts, Thomas

AU - Stephens, Christine

AU - Ditta, Shabana

AU - Shepherdson, Rebecca

AU - Powell, Annabel A.

AU - Brent, Andrew J.

AU - Brent, Bernadette

AU - Baawuah, Frances

AU - Okike, Ifeanyichukwu

AU - Beckmann, Joanne

AU - Ahmad, Shazaad

AU - Aiano, Felicity

AU - Garstang, Joanna

AU - Ramsay, Mary E.

AU - Azad, Rafaq

AU - Waiblinger, Dagmar

AU - Willett, Brian

AU - Wright, John

AU - Ladhani, Shamez N.

AU - Moss, Paul

PY - 2023/6/29

Y1 - 2023/6/29

N2 - Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.

AB - Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.

U2 - 10.1038/s41467-023-39575-2

DO - 10.1038/s41467-023-39575-2

M3 - Article

C2 - 37386081

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3845

ER -

Immunological imprinting of humoral immunity to SARS-CoV-2 in children

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COVID-19 Immunity - National Core Study (IMM-NCS)

A UK underpinning platform to study immunology and immunopathology of COVID-19:The UK Coronavirus Immunology Consortium

Cite this