Nasal mucosal IgA levels against SARS-CoV-2 and seasonal coronaviruses are low in children but boosted by reinfection

Alexander C. Dowell; Gokhan Tut; Jusnara Begum; Rachel Bruton; Christopher Bentley; Megan Butler; Grace Uwenedi; Jianmin Zuo; Annabel A. Powell; Andrew J. Brent; Bernadette Brent; Frances Baawuah; Ifeanyichukwu Okike; Joanne Beckmann; Shazaad Ahmad; Felicity Aiano; Joanna Garstang; Mary E. Ramsay; Paul Moss; Shamez N. Ladhani

doi:10.1016/j.jinf.2023.08.013

Nasal mucosal IgA levels against SARS-CoV-2 and seasonal coronaviruses are low in children but boosted by reinfection

Alexander C. Dowell, Gokhan Tut, Jusnara Begum, Rachel Bruton, Christopher Bentley, Megan Butler, Grace Uwenedi, Jianmin Zuo, Annabel A. Powell, Andrew J. Brent, Bernadette Brent, Frances Baawuah, Ifeanyichukwu Okike, Joanne Beckmann, Shazaad Ahmad, Felicity Aiano, Joanna Garstang, Mary E. Ramsay, Paul Moss^*, Shamez N. Ladhani^*

^*Corresponding author for this work

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

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Abstract

Repeated coronavirus infections in childhood drive progressive maturation of systemic immune responses into adulthood. Analyses of immune responses in children have focused primarily upon systemic assessment but the importance of mucosal immunity is increasingly recognised. We studied virus-specific antibody responses in contemporaneous nasal swabs and blood samples from 99 children (4–15 years) and 28 adults (22–56 years), all of whom had prior SARS-CoV-2 infection. Whilst mucosal IgA titres against Influenza and Respiratory Syncytial virus were comparable between children and adults, those against all coronaviruses, including SARS-CoV-2, were lower in children. Mucosal IgA antibodies demonstrated comparable relative neutralisation capacity in both groups and retained activity against recent omicron variants such as XBB.1 which are highly evasive of IgG neutralisation. SARS-CoV-2 reinfection preferentially enhanced mucosal IgA responses whilst the impact of vaccination was more modest. Nasal IgA levels against coronaviruses thus display a pattern of incremental response to reinfection which likely determines the natural history of reinfection. This highlights the particular significance of developing mucosal vaccines against coronaviruses in children.

Original language	English
Pages (from-to)	403-412
Number of pages	10
Journal	Journal of Infection
Volume	87
Issue number	5
Early online date	3 Sept 2023
DOIs	https://doi.org/10.1016/j.jinf.2023.08.013
Publication status	Published - Nov 2023

Bibliographical note

Acknowledgements:
This study was funded by the Medical Research Council (MRC) UK Coronavirus Immunology Consortium (UK-CIC, MR/V028448/1) and the National Core Studies (NCS) programme (MC_PC_20031) awarded to PM.

Copyright:
© 2023 The Authors. Published by Elsevier Ltd.

Keywords

Mucosal
IgA
Respiratory pathogens
Coronavirus
SARS-CoV-2
Paediatric

UN SDGs

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

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10.1016/j.jinf.2023.08.013Licence: Creative Commons: Attribution (CC BY)

DowellA2023NasalFinal published version, 3.11 MBLicence: Creative Commons: Attribution (CC BY)

The UK Coronavirus Immunology Consortium asymptomatic paediatric project
Wraith, D. (Researcher), Duggal, N. (Researcher), Long, H. (Researcher), Zuo, J. (Researcher), Lord, J. (Researcher), Moss, P. (Principal Investigator) & Taylor, G. (Researcher)
Medical Research Council
20/08/20 → 19/08/21
Project: Research Councils

Cite this

Dowell, A. C., Tut, G., Begum, J., Bruton, R., Bentley, C., Butler, M., Uwenedi, G., Zuo, J., Powell, A. A., Brent, A. J., Brent, B., Baawuah, F., Okike, I., Beckmann, J., Ahmad, S., Aiano, F., Garstang, J., Ramsay, M. E., Moss, P., & Ladhani, S. N. (2023). Nasal mucosal IgA levels against SARS-CoV-2 and seasonal coronaviruses are low in children but boosted by reinfection. Journal of Infection, 87(5), 403-412. https://doi.org/10.1016/j.jinf.2023.08.013

@article{39065ef0127f438eb7040e3144766d1c,

title = "Nasal mucosal IgA levels against SARS-CoV-2 and seasonal coronaviruses are low in children but boosted by reinfection",

abstract = "Repeated coronavirus infections in childhood drive progressive maturation of systemic immune responses into adulthood. Analyses of immune responses in children have focused primarily upon systemic assessment but the importance of mucosal immunity is increasingly recognised. We studied virus-specific antibody responses in contemporaneous nasal swabs and blood samples from 99 children (4–15 years) and 28 adults (22–56 years), all of whom had prior SARS-CoV-2 infection. Whilst mucosal IgA titres against Influenza and Respiratory Syncytial virus were comparable between children and adults, those against all coronaviruses, including SARS-CoV-2, were lower in children. Mucosal IgA antibodies demonstrated comparable relative neutralisation capacity in both groups and retained activity against recent omicron variants such as XBB.1 which are highly evasive of IgG neutralisation. SARS-CoV-2 reinfection preferentially enhanced mucosal IgA responses whilst the impact of vaccination was more modest. Nasal IgA levels against coronaviruses thus display a pattern of incremental response to reinfection which likely determines the natural history of reinfection. This highlights the particular significance of developing mucosal vaccines against coronaviruses in children.",

keywords = "Mucosal, IgA, Respiratory pathogens, Coronavirus, SARS-CoV-2, Paediatric",

author = "Dowell, {Alexander C.} and Gokhan Tut and Jusnara Begum and Rachel Bruton and Christopher Bentley and Megan Butler and Grace Uwenedi and Jianmin Zuo 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 Paul Moss and Ladhani, {Shamez N.}",

note = "Acknowledgements: This study was funded by the Medical Research Council (MRC) UK Coronavirus Immunology Consortium (UK-CIC, MR/V028448/1) and the National Core Studies (NCS) programme (MC_PC_20031) awarded to PM. Copyright: {\textcopyright} 2023 The Authors. Published by Elsevier Ltd.",

year = "2023",

month = nov,

doi = "10.1016/j.jinf.2023.08.013",

language = "English",

volume = "87",

pages = "403--412",

journal = "Journal of Infection",

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Dowell, AC , Tut, G, Begum, J, Bruton, R, Bentley, C, Butler, M, Uwenedi, G, Zuo, J, Powell, AA, Brent, AJ, Brent, B, Baawuah, F, Okike, I, Beckmann, J, Ahmad, S, Aiano, F, Garstang, J, Ramsay, ME, Moss, P & Ladhani, SN 2023, 'Nasal mucosal IgA levels against SARS-CoV-2 and seasonal coronaviruses are low in children but boosted by reinfection', Journal of Infection, vol. 87, no. 5, pp. 403-412. https://doi.org/10.1016/j.jinf.2023.08.013

TY - JOUR

T1 - Nasal mucosal IgA levels against SARS-CoV-2 and seasonal coronaviruses are low in children but boosted by reinfection

AU - Dowell, Alexander C.

AU - Tut, Gokhan

AU - Begum, Jusnara

AU - Bruton, Rachel

AU - Bentley, Christopher

AU - Butler, Megan

AU - Uwenedi, Grace

AU - Zuo, Jianmin

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 - Moss, Paul

AU - Ladhani, Shamez N.

N1 - Acknowledgements: This study was funded by the Medical Research Council (MRC) UK Coronavirus Immunology Consortium (UK-CIC, MR/V028448/1) and the National Core Studies (NCS) programme (MC_PC_20031) awarded to PM. Copyright: © 2023 The Authors. Published by Elsevier Ltd.

PY - 2023/11

Y1 - 2023/11

N2 - Repeated coronavirus infections in childhood drive progressive maturation of systemic immune responses into adulthood. Analyses of immune responses in children have focused primarily upon systemic assessment but the importance of mucosal immunity is increasingly recognised. We studied virus-specific antibody responses in contemporaneous nasal swabs and blood samples from 99 children (4–15 years) and 28 adults (22–56 years), all of whom had prior SARS-CoV-2 infection. Whilst mucosal IgA titres against Influenza and Respiratory Syncytial virus were comparable between children and adults, those against all coronaviruses, including SARS-CoV-2, were lower in children. Mucosal IgA antibodies demonstrated comparable relative neutralisation capacity in both groups and retained activity against recent omicron variants such as XBB.1 which are highly evasive of IgG neutralisation. SARS-CoV-2 reinfection preferentially enhanced mucosal IgA responses whilst the impact of vaccination was more modest. Nasal IgA levels against coronaviruses thus display a pattern of incremental response to reinfection which likely determines the natural history of reinfection. This highlights the particular significance of developing mucosal vaccines against coronaviruses in children.

AB - Repeated coronavirus infections in childhood drive progressive maturation of systemic immune responses into adulthood. Analyses of immune responses in children have focused primarily upon systemic assessment but the importance of mucosal immunity is increasingly recognised. We studied virus-specific antibody responses in contemporaneous nasal swabs and blood samples from 99 children (4–15 years) and 28 adults (22–56 years), all of whom had prior SARS-CoV-2 infection. Whilst mucosal IgA titres against Influenza and Respiratory Syncytial virus were comparable between children and adults, those against all coronaviruses, including SARS-CoV-2, were lower in children. Mucosal IgA antibodies demonstrated comparable relative neutralisation capacity in both groups and retained activity against recent omicron variants such as XBB.1 which are highly evasive of IgG neutralisation. SARS-CoV-2 reinfection preferentially enhanced mucosal IgA responses whilst the impact of vaccination was more modest. Nasal IgA levels against coronaviruses thus display a pattern of incremental response to reinfection which likely determines the natural history of reinfection. This highlights the particular significance of developing mucosal vaccines against coronaviruses in children.

KW - Mucosal

KW - IgA

KW - Respiratory pathogens

KW - Coronavirus

KW - SARS-CoV-2

KW - Paediatric

U2 - 10.1016/j.jinf.2023.08.013

DO - 10.1016/j.jinf.2023.08.013

M3 - Article

C2 - 37660754

SN - 0163-4453

VL - 87

SP - 403

EP - 412

JO - Journal of Infection

JF - Journal of Infection

IS - 5

ER -

Nasal mucosal IgA levels against SARS-CoV-2 and seasonal coronaviruses are low in children but boosted by reinfection

Abstract

Bibliographical note

Keywords

UN SDGs

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Projects

The UK Coronavirus Immunology Consortium asymptomatic paediatric project

Cite this