Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal antibody and T cell immunity

Barbara Kronsteiner; Melissa Govender; Chang Liu; Aiste Dijokaite-Guraliuc; Mohammad Ali; Jennifer Hill; Martha Zewdie; Andrew Cross; James Austin; Amyleigh Watts; Adrienn Angyal; Hailey Hornsby; Priyanka Abraham; Sandra Adele; Srija Moulik; Jodie Harte; Alexander Hargreaves; Yasmin Jiwa; Muneeswaran Selvaraj; Lizzie Stafford; Anni Jamsen; Susan L Dobson; Sofia Sampaio; Callum Halstead; Amy Steel; Stephanie Longet; Sian E Faustini; Shona C Moore; Juthathip Mongkolsapaya; Daniel G Wootton; James E D Thaventhiran; Susan Hopkins; Victoria Hall; Katie Jeffery; Eleanor Barnes; Christopher J A Duncan; Rebecca P Payne; Alex G Richter; Thushan I de Silva; Lance Turtle; Gavin R Screaton; Paul Klenerman; Miles Carroll; Susanna J Dunachie; PITCH Consortium

doi:10.1038/s41598-025-28310-0

Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal antibody and T cell immunity

Barbara Kronsteiner^*
, Melissa Govender
, Chang Liu
, Aiste Dijokaite-Guraliuc
, Mohammad Ali
, Jennifer Hill
, Martha Zewdie
, Andrew Cross
, James Austin
, Amyleigh Watts
, Adrienn Angyal
, Hailey Hornsby
, Priyanka Abraham
, Sandra Adele
, Srija Moulik
, Jodie Harte
, Alexander Hargreaves
, Yasmin Jiwa
, Muneeswaran Selvaraj
, Lizzie Stafford

Anni Jamsen, Susan L Dobson, Sofia Sampaio, Callum Halstead, Amy Steel, Stephanie Longet, Sian E Faustini, Shona C Moore, Juthathip Mongkolsapaya, Daniel G Wootton, James E D Thaventhiran, Susan Hopkins, Victoria Hall, Katie Jeffery, Eleanor Barnes, Christopher J A Duncan, Rebecca P Payne, Alex G Richter, Thushan I de Silva, Lance Turtle, Gavin R Screaton, Paul Klenerman, Miles Carroll, Susanna J Dunachie^*, PITCH Consortium

^*Corresponding author for this work

Immunology and Immunotherapy

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

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Abstract

COVID-19 vaccines were updated to address immune escape from variants of concern (VOC). We explored the impact of ancestral/BA.1 bivalent mRNA booster vaccination (Autumn 2022) on peripheral and nasal antibody and T-cell responses to SARS-CoV-2 in an observational cohort of 133 healthcare workers, building on previous longitudinal vaccination studies. We demonstrate that maintenance of antibody and T-cell responses up to eighteen months following the third vaccine is at least partially driven by intercurrent infection. Boosting with the bivalent vaccine increases the breadth of circulating and nasal antibodies to spike, which waned over time but was still detectable six months post-dose. T-cell responses are well maintained and highly cross-reactive to VOCs irrespective of booster vaccination. Vaccination strongly boosted nasal IgG, but this was short-lived compared to circulating antibodies. Overall, ongoing COVID-19 vaccination provides benefit, boosting immunity in individuals who have not been recently infected, but new strategies may be needed to provide longer-term nasal immunity.

Original language	English
Journal	Scientific Reports
Early online date	27 Nov 2025
DOIs	https://doi.org/10.1038/s41598-025-28310-0
Publication status	E-pub ahead of print - 27 Nov 2025

Bibliographical note

UN SDGs

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

SDG 3 Good Health and Well-being

Access to Document

10.1038/s41598-025-28310-0Licence: Creative Commons: Attribution (CC BY)

KronsteinerB2025Dynamic_AAMonlineAccepted author manuscript, 940 KBLicence: Creative Commons: Attribution (CC BY)

Protective Immunity through T Cells in Healthcare workers 2
Richter, A. (Principal Investigator), Shields, A. (Co-Investigator) & Faustini, S. (Researcher)
Medical Research Council
1/01/23 → 31/12/24
Project: Research Councils
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

Kronsteiner, B., Govender, M., Liu, C., Dijokaite-Guraliuc, A., Ali, M., Hill, J., Zewdie, M., Cross, A., Austin, J., Watts, A., Angyal, A., Hornsby, H., Abraham, P., Adele, S., Moulik, S., Harte, J., Hargreaves, A., Jiwa, Y., Selvaraj, M., ... PITCH Consortium (2025). Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal antibody and T cell immunity. Scientific Reports. Advance online publication. https://doi.org/10.1038/s41598-025-28310-0

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title = "Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal antibody and T cell immunity",

abstract = "COVID-19 vaccines were updated to address immune escape from variants of concern (VOC). We explored the impact of ancestral/BA.1 bivalent mRNA booster vaccination (Autumn 2022) on peripheral and nasal antibody and T-cell responses to SARS-CoV-2 in an observational cohort of 133 healthcare workers, building on previous longitudinal vaccination studies. We demonstrate that maintenance of antibody and T-cell responses up to eighteen months following the third vaccine is at least partially driven by intercurrent infection. Boosting with the bivalent vaccine increases the breadth of circulating and nasal antibodies to spike, which waned over time but was still detectable six months post-dose. T-cell responses are well maintained and highly cross-reactive to VOCs irrespective of booster vaccination. Vaccination strongly boosted nasal IgG, but this was short-lived compared to circulating antibodies. Overall, ongoing COVID-19 vaccination provides benefit, boosting immunity in individuals who have not been recently infected, but new strategies may be needed to provide longer-term nasal immunity.",

author = "Barbara Kronsteiner and Melissa Govender and Chang Liu and Aiste Dijokaite-Guraliuc and Mohammad Ali and Jennifer Hill and Martha Zewdie and Andrew Cross and James Austin and Amyleigh Watts and Adrienn Angyal and Hailey Hornsby and Priyanka Abraham and Sandra Adele and Srija Moulik and Jodie Harte and Alexander Hargreaves and Yasmin Jiwa and Muneeswaran Selvaraj and Lizzie Stafford and Anni Jamsen and Dobson, \{Susan L\} and Sofia Sampaio and Callum Halstead and Amy Steel and Stephanie Longet and Faustini, \{Sian E\} and Moore, \{Shona C\} and Juthathip Mongkolsapaya and Wootton, \{Daniel G\} and Thaventhiran, \{James E D\} and Susan Hopkins and Victoria Hall and Katie Jeffery and Eleanor Barnes and Duncan, \{Christopher J A\} and Payne, \{Rebecca P\} and Richter, \{Alex G\} and \{de Silva\}, \{Thushan I\} and Lance Turtle and Screaton, \{Gavin R\} and Paul Klenerman and Miles Carroll and Dunachie, \{Susanna J\} and \{PITCH Consortium\}",

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doi = "10.1038/s41598-025-28310-0",

language = "English",

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Kronsteiner, B, Govender, M, Liu, C, Dijokaite-Guraliuc, A, Ali, M, Hill, J, Zewdie, M, Cross, A, Austin, J, Watts, A, Angyal, A, Hornsby, H, Abraham, P, Adele, S, Moulik, S, Harte, J, Hargreaves, A, Jiwa, Y, Selvaraj, M, Stafford, L, Jamsen, A, Dobson, SL, Sampaio, S, Halstead, C, Steel, A, Longet, S, Faustini, SE, Moore, SC, Mongkolsapaya, J, Wootton, DG, Thaventhiran, JED, Hopkins, S, Hall, V, Jeffery, K, Barnes, E, Duncan, CJA, Payne, RP, Richter, AG, de Silva, TI, Turtle, L, Screaton, GR, Klenerman, P, Carroll, M, Dunachie, SJ & PITCH Consortium 2025, 'Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal antibody and T cell immunity', Scientific Reports. https://doi.org/10.1038/s41598-025-28310-0

TY - JOUR

T1 - Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal antibody and T cell immunity

AU - Kronsteiner, Barbara

AU - Govender, Melissa

AU - Liu, Chang

AU - Dijokaite-Guraliuc, Aiste

AU - Ali, Mohammad

AU - Hill, Jennifer

AU - Zewdie, Martha

AU - Cross, Andrew

AU - Austin, James

AU - Watts, Amyleigh

AU - Angyal, Adrienn

AU - Hornsby, Hailey

AU - Abraham, Priyanka

AU - Adele, Sandra

AU - Moulik, Srija

AU - Harte, Jodie

AU - Hargreaves, Alexander

AU - Jiwa, Yasmin

AU - Selvaraj, Muneeswaran

AU - Stafford, Lizzie

AU - Jamsen, Anni

AU - Dobson, Susan L

AU - Sampaio, Sofia

AU - Halstead, Callum

AU - Steel, Amy

AU - Longet, Stephanie

AU - Faustini, Sian E

AU - Moore, Shona C

AU - Mongkolsapaya, Juthathip

AU - Wootton, Daniel G

AU - Thaventhiran, James E D

AU - Hopkins, Susan

AU - Hall, Victoria

AU - Jeffery, Katie

AU - Barnes, Eleanor

AU - Duncan, Christopher J A

AU - Payne, Rebecca P

AU - Richter, Alex G

AU - de Silva, Thushan I

AU - Turtle, Lance

AU - Screaton, Gavin R

AU - Klenerman, Paul

AU - Carroll, Miles

AU - Dunachie, Susanna J

AU - PITCH Consortium

PY - 2025/11/27

Y1 - 2025/11/27

N2 - COVID-19 vaccines were updated to address immune escape from variants of concern (VOC). We explored the impact of ancestral/BA.1 bivalent mRNA booster vaccination (Autumn 2022) on peripheral and nasal antibody and T-cell responses to SARS-CoV-2 in an observational cohort of 133 healthcare workers, building on previous longitudinal vaccination studies. We demonstrate that maintenance of antibody and T-cell responses up to eighteen months following the third vaccine is at least partially driven by intercurrent infection. Boosting with the bivalent vaccine increases the breadth of circulating and nasal antibodies to spike, which waned over time but was still detectable six months post-dose. T-cell responses are well maintained and highly cross-reactive to VOCs irrespective of booster vaccination. Vaccination strongly boosted nasal IgG, but this was short-lived compared to circulating antibodies. Overall, ongoing COVID-19 vaccination provides benefit, boosting immunity in individuals who have not been recently infected, but new strategies may be needed to provide longer-term nasal immunity.

AB - COVID-19 vaccines were updated to address immune escape from variants of concern (VOC). We explored the impact of ancestral/BA.1 bivalent mRNA booster vaccination (Autumn 2022) on peripheral and nasal antibody and T-cell responses to SARS-CoV-2 in an observational cohort of 133 healthcare workers, building on previous longitudinal vaccination studies. We demonstrate that maintenance of antibody and T-cell responses up to eighteen months following the third vaccine is at least partially driven by intercurrent infection. Boosting with the bivalent vaccine increases the breadth of circulating and nasal antibodies to spike, which waned over time but was still detectable six months post-dose. T-cell responses are well maintained and highly cross-reactive to VOCs irrespective of booster vaccination. Vaccination strongly boosted nasal IgG, but this was short-lived compared to circulating antibodies. Overall, ongoing COVID-19 vaccination provides benefit, boosting immunity in individuals who have not been recently infected, but new strategies may be needed to provide longer-term nasal immunity.

U2 - 10.1038/s41598-025-28310-0

DO - 10.1038/s41598-025-28310-0

M3 - Article

C2 - 41310059

SN - 2045-2322

JO - Scientific Reports

JF - Scientific Reports

ER -

Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal antibody and T cell immunity

Abstract

Bibliographical note

UN SDGs

Access to Document

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Projects

Protective Immunity through T Cells in Healthcare workers 2

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

Cite this