Mucosal immune responses to SARS-CoV-2 infection and COVID-19 vaccination

Mathew J Paul; Mohammed T Hudda; Scott Pallett; Elisabetta Groppelli; Eugenia Boariu; Nicole Falci Finardi; Rachel Wake; Nidhi Sofat; Kathryn Biddle; Soraya Koushesh; Louis Dwyer-Hemmings; Richard Cook; Julian K-C Ma

doi:10.1016/j.vaccine.2025.127175

Mucosal immune responses to SARS-CoV-2 infection and COVID-19 vaccination

Vaccine. 2025 May 22:56:127175. doi: 10.1016/j.vaccine.2025.127175. Epub 2025 Apr 30.

Authors

Affiliations

¹ Institute for Infection and Immunity, City St. George's University of London, Cranmer Terrace, London SW17 0RE, UK. Electronic address: mpaul@sgul.ac.uk.
² Department of Population Health, Dasman Institute, Jasim Mohamad Al Bahar St, Kuwait City, Kuwait. Electronic address: mohammedhudda@dasmaninstitute.org.
³ Institute for Infection and Immunity, City St. George's University of London, Cranmer Terrace, London SW17 0RE, UK; Centre of Defence Pathology, Royal Centre of Defence Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2WB, UK; St. George's University Hospitals NHS Foundation Trust, Blackshaw Road Tooting, London SW17 0QT, UK. Electronic address: scottpallett@nhs.net.
⁴ Institute for Infection and Immunity, City St. George's University of London, Cranmer Terrace, London SW17 0RE, UK. Electronic address: egroppel@sgul.ac.uk.
⁵ Institute for Infection and Immunity, City St. George's University of London, Cranmer Terrace, London SW17 0RE, UK.
⁶ Institute for Infection and Immunity, City St. George's University of London, Cranmer Terrace, London SW17 0RE, UK. Electronic address: nfinardi@sgul.ac.uk.
⁷ Institute for Infection and Immunity, City St. George's University of London, Cranmer Terrace, London SW17 0RE, UK; St. George's University Hospitals NHS Foundation Trust, Blackshaw Road Tooting, London SW17 0QT, UK. Electronic address: rachel.wake1@nhs.net.
⁸ Institute for Infection and Immunity, City St. George's University of London, Cranmer Terrace, London SW17 0RE, UK; St. George's University Hospitals NHS Foundation Trust, Blackshaw Road Tooting, London SW17 0QT, UK. Electronic address: nsofat@sgul.ac.uk.
⁹ Institute for Infection and Immunity, City St. George's University of London, Cranmer Terrace, London SW17 0RE, UK; St. George's University Hospitals NHS Foundation Trust, Blackshaw Road Tooting, London SW17 0QT, UK. Electronic address: Kathryn.biddle@nhs.net.
¹⁰ Institute for Infection and Immunity, City St. George's University of London, Cranmer Terrace, London SW17 0RE, UK. Electronic address: skoushes@sgul.ac.uk.
¹¹ Institute for Infection and Immunity, City St. George's University of London, Cranmer Terrace, London SW17 0RE, UK; St. George's University Hospitals NHS Foundation Trust, Blackshaw Road Tooting, London SW17 0QT, UK.
¹² Faculty of Dentistry, Oral & Craniofacial Sciences, Kings College London, Floor 22, Guy's Tower, Guy's Hospital, Great Maze Pond, London, SE1 1UL, UK. Electronic address: richard_james.cook@kcl.ac.uk.
¹³ Institute for Infection and Immunity, City St. George's University of London, Cranmer Terrace, London SW17 0RE, UK; St. George's University Hospitals NHS Foundation Trust, Blackshaw Road Tooting, London SW17 0QT, UK. Electronic address: jma@sgul.ac.uk.

PMID: 40311214
DOI: 10.1016/j.vaccine.2025.127175

Abstract

SARS-CoV-2 continues to circulate in the community. We hypothesise that mucosal immunity is required to prevent continuing viral acquisition and transmission.

Objectives: To determine whether SARS-CoV-2 infection or vaccination elicits specific neutralising antibodies in saliva, and to assess the longevity of protection.

Methods: Initially, 111 COVID-19 convalescent participants were recruited, 11-369 days after diagnosis. Saliva and blood samples were assayed for antibodies specific for Spike protein, Receptor Binding Domain and Nucleoprotein. In a second cohort, 123 participants were recruited. Saliva and serum antibodies to the same antigens were assayed before and after their first and second COVID-19 vaccinations, with 150 day follow up.

Results: Natural infection induces and boosts IgA and IgG in oral fluid and serum; vaccination does not induce or boost specific saliva IgA; IgG can be found in saliva after vaccination, but only when serum IgG concentrations are high; IgA is important for SARS-CoV-2 neutralisation activity by oral fluid, but there can also be contributions from serum IgG and other factors.

Conclusions: New COVID-19 vaccines should target both systemic and mucosal immunity, to establish a first line of immune defence at the mucosal barrier. This would benefit vulnerable patient populations and may help to eradicate SARS-CoV-2 circulation.

Keywords: COVID-19; Immune response; Mucosal immunity; Neutralising antibody; Oral fluid IgA; SARS-CoV-2; Saliva; Vaccination.

MeSH terms

Adult
Aged
Antibodies, Neutralizing / blood
Antibodies, Neutralizing / immunology
Antibodies, Viral / analysis
Antibodies, Viral / blood
Antibodies, Viral / immunology
COVID-19 Vaccines* / administration & dosage
COVID-19 Vaccines* / immunology
COVID-19* / immunology
COVID-19* / prevention & control
Female
Humans
Immunity, Mucosal*
Immunoglobulin A / blood
Immunoglobulin A / immunology
Immunoglobulin G / blood
Immunoglobulin G / immunology
Male
Middle Aged
SARS-CoV-2* / immunology
Saliva / immunology
Spike Glycoprotein, Coronavirus / immunology
Vaccination
Young Adult

Substances

Antibodies, Viral
Immunoglobulin G
COVID-19 Vaccines
Immunoglobulin A
Antibodies, Neutralizing
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2