Stephanie Longet

Conference 2023 Live Talk

Talk title

COVID-19 mRNA vaccination drives differential mucosal neutralising antibody profiles in naïve and SARS-CoV-2 previously infected individuals

Authors and Affiliations

Stephanie Longet1, Alexander Hargreaves1, Saoirse Healy1, Rebecca Brown2, Hailey R Hornsby2, Naomi Meardon3, Tom Tipton1, Eleanor Barnes4,5, Susanna Dunachie4,5,6,7, Christopher JA Duncan8,9, Paul Klenerman4,5,10,11, Alex Richter12,13, Lance Turtle14,15, Thushan I. de Silva2,3^, Miles W. Carroll1,16^on behalf of the PITCH Consortium

1. Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford United Kingdom
2. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK
3. Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
4. Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford, UK
5. Oxford University Hospitals NHS Foundation Trust, Oxford, UK
6. Oxford Centre For Global Health Research, Nuffield Dept. of Clinical Medicine, University of Oxford, UK
7. Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand
8. Translational and Clinical Research Institute Immunity and Inflammation Theme, Newcastle University
9. Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, UK
10. Translational Gastroenterology Unit, University of Oxford, UK
11. NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
12. Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, UK
13. University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
14. NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK
15. Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
16. Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford United Kingdom
^ Joint senior author

Abstract

Background

SARS-CoV-2 licensed vaccines are efficacious for preventing severe disease. However, the current approved COVID-19 vaccines are administered intramuscularly which may not reflect the most efficient route to induce mucosal immunity protecting against transmission.

Methods

We performed a comparative analysis of SARS-CoV-2 IgG, IgA and neutralizing responses before and after 1st, 2nd and 3rd mRNA vaccine dose in oral fluid and plasma from 200 healthcare workers who were naïve or SARS-CoV-2 previously-infected using MSD® pan-coronavirus multiplex binding and ACE2 inhibition assays.

Results

Prior to vaccination, we found that spike-specific IgG levels in oral fluid positively correlated with IgG levels in plasma from previously-infected individuals demonstrating that oral fluid could be used as a proxy for the presence of plasma SARS-CoV-2 IgG. However, the sensitivity was lower in oral fluid than in plasma. Similar kinetics of mucosal and systemic spike-specific IgG levels were observed following vaccination in naïve and previously-infected individuals, respectively. Mucosal spike-specific IgA responses were induced by mRNA vaccination particularly in previously-infected individuals but less frequently in naïve participants. Neutralizing responses to SARS-CoV-2 ancestral and variants of concerns were detected following vaccination in naïve and previously-infected participants, with likely contribution from both IgG and IgA in previously-infected individuals. Breakthrough infections or a third vaccine dose also enhanced mucosal antibody levels and neutralizing responses.

Conclusions

These data contribute to show that a previous SARS-CoV-2 infection tailors the mucosal antibody profile induced by vaccination.