Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal antibody and T cell immunity
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.
Authors
- Priyanka Abraham (ORCID: https://orcid.org/0000-0002-5296-4499)
- Srija Moulik (ORCID: https://orcid.org/0000-0001-5286-2831)
- Alexander Hargreaves (ORCID: https://orcid.org/0000-0002-7156-1521)
- Mohammad Ali (ORCID: https://orcid.org/0000-0002-4765-615X)
- Brendan Payne (ORCID: https://orcid.org/0000-0002-3101-3512)
- Dan Gower Wootton (ORCID: https://orcid.org/0000-0002-5903-3881)
- Victoria Hall (ORCID: https://orcid.org/0000-0001-8744-4277)
- Sian Faustini (ORCID: https://orcid.org/0000-0002-9300-5569)
- James Austin (ORCID: https://orcid.org/0000-0002-5384-5221)
- Katie Jeffery (ORCID: https://orcid.org/0000-0002-6506-2689)
- Eleanor Barnes (ORCID: https://orcid.org/0000-0002-0860-0831)
- Paul Klenerman (ORCID: https://orcid.org/0000-0003-4307-9161)
- Susan Hopkins (ORCID: https://orcid.org/0000-0001-5179-5702)
- Clynton W. Halstead
- Aiste Dijokaite-Guraliuc (ORCID: https://orcid.org/0000-0002-4850-9709)
- James Thaventhiran (ORCID: https://orcid.org/0000-0001-8616-074X)
- Alex Richter (ORCID: https://orcid.org/0000-0003-2885-1299)
- Anni Jämsén
- Susan L. Dobson (ORCID: https://orcid.org/0000-0002-4958-0021)
- Melissa Govender (ORCID: https://orcid.org/0000-0001-8327-5517)
- Muneeswaran Selvaraj
- Lizzie Stafford (ORCID: https://orcid.org/0000-0002-1610-5136)
- Adam Steel (ORCID: https://orcid.org/0000-0001-8876-933X)
- Thushan I. de Silva (ORCID: https://orcid.org/0000-0002-6498-9212)
- Stéphanie Longet (ORCID: https://orcid.org/0000-0001-5026-431X)
- Amyleigh Watts
- Barbara Kronsteiner (ORCID: https://orcid.org/0000-0003-0867-2867)
- Miles W. Carroll (ORCID: https://orcid.org/0000-0002-7026-7187)
- Adrienn Angyal (ORCID: https://orcid.org/0000-0001-8483-1749)
- Sandra Adele (ORCID: https://orcid.org/0000-0003-4458-1751)
- C.J. Duncan (ORCID: https://orcid.org/0000-0003-4181-2315)
- Susanna Dunachie (ORCID: https://orcid.org/0000-0001-5665-6293)
- Hailey Hornsby (ORCID: https://orcid.org/0000-0002-6657-9743)
- Jennifer W Hill (ORCID: https://orcid.org/0000-0001-6205-7764)
- Shona C. Moore (ORCID: https://orcid.org/0000-0001-8610-2806)
- Lance C. W. Turtle (ORCID: https://orcid.org/0000-0002-0778-1693)
- Susana Sampaio (ORCID: https://orcid.org/0000-0002-9959-4931)
- Gavin Robert Screaton (ORCID: https://orcid.org/0000-0002-3549-4309)
- Martha Zewdie (ORCID: https://orcid.org/0000-0003-2155-5550)
- Chang Liu (ORCID: https://orcid.org/0009-0008-8169-4572)
- Andrew Cross
- Juthathip Mongkolsapaya
- Jodie Harte
- Yasmin Jiwa
Institutions
- Université Claude Bernard Lyon 1 (FR)
- National Security Agency (US)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Centre for Human Genetics (GB)
- University of Liverpool (GB)
- Inserm (FR)
- University of Cambridge (GB)
- Aintree University Hospitals NHS Foundation Trust (GB)
- Angkor Hospital for Children (KH)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- University of Oxford (GB)
- Medawar Building for Pathogen Research (GB)
- Sheffield Teaching Hospitals NHS Foundation Trust (GB)
- Nuffield Health (GB)
- Mahidol Oxford Tropical Medicine Research Unit (TH)
- Oxford BioMedica (United Kingdom) (GB)
- Oxford University Hospitals NHS Trust (GB)
- Centre International de Recherche en Infectiologie (FR)
- Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool (GB)
- Imperial College London (GB)
- University of Birmingham (GB)
- Newcastle University (GB)
- Medical Research Council (GB)
- University of Sheffield (GB)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-11-27
- DOI
- https://doi.org/10.1038/s41598-025-28310-0
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wellcome Trust
- British Society for Immunology
- UK Research and Innovation
- Coalition for Epidemic Preparedness Innovations
- National Institute for Health Research Health Protection Research Unit
- National Institute for Health and Care Research
- British Heart Foundation
- Department of Health and Social Care
- University of Oxford
- Chinese Academy of Medical Sciences
- UK Coronavirus Immunology Consortium
- U.S. Food and Drug Administration
- Medical Research Council
- NIHR Oxford Biomedical Research Centre